Training with low muscle glycogen enhances fat metabolism

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Cellular Metabolic Response To Hypoxia

Although cellular metabolic responses to hypoxia remain poorly understood, the importance of understanding and modifying the cellular responses to acute hypoxia in the critically ill patient has recently been appreciated. In isolated mitochondria the partial pressure of oxygen required to generate high energy phosphate bonds (ATP) that maintain aerobic cellular biochemical functions is only about 0.20.4 kPa.17 28 However, in intact cell preparations hypoxia induced damage may result from failure of energy dependent membrane ion channels with subsequent loss of membrane integrity, changes in cellular calcium homeostasis, and oxygen dependent changes in cellular enzyme activity.28 The sensitivity of an enzyme to hypoxia is a function of its Po2 in mm Hg at which the enzyme rate is half maximum (Kmo2),28 and the wide range of values for a variety of cellular enzymes is shown in table 2.2, illustrating that certain metabolic functions are much more sensitive to hypoxia than others....

Growth Hormone Has Several Metabolic Effects

Effects Growth Hormone Cellebrities

Aside from its general effect in causing growth, growth hormone has multiple specific metabolic effects, Each of these changes results from growth hormone-induced insulin resistance, which attenuates insulin's actions to stimulate the uptake and utilization of glucose in skeletal muscle and fat and to inhibit gluconeogenesis (glucose production) by the liver this leads to increased blood glucose concentration and a compensatory increase in insulin secretion. For these reasons, growth hormone's effects are called diabetogenic, and excess secretion of growth hormone can produce metabolic disturbances very similar to those found in patients with type II (non-insulin-dependent) diabetes, who are also very resistant to the metabolic effects of insulin.

Energy Metabolism Factors That Influence Energy Output

As discussed in Chapter 71, energy intake is balanced with energy output in healthy adults who maintain a stable body weight. About 45 per cent of daily energy intake is derived from carbohydrates, 40 per cent from fats, and 15 per cent from proteins in the average American diet. Energy output can also be partitioned into several measurable components, including energy used for (1) performing essential metabolic functions of the body (the basal metabolic rate) (2) performing various physical activities (3) digesting, absorbing, and processing food and (4) maintaining body temperature. Basal Metabolic Rate (BMR) The Minimum Energy Expenditure for the Body to Exist Even when a person is at complete rest, considerable energy is required to perform all the chemical reactions of the body. This minimum level of energy required to exist is called the basal metabolic rate (BMR) and accounts for about 50 to 70 per cent of the daily energy expenditure in most sedentary individuals (Figure...

Pharmacological actions Energy metabolism

Steviol interferes with energy metabolism in rat renal tubules, blocking oxygen uptake and glucose production (Yamamoto et al. 1985). Gluconeogenesis is inhibited 50 at 0.3 mM steviol, and complete inhibition is produced at 1 mM. Oxygen uptake is inhibited 50 at 0.4 mM steviol in the presence ofpyruvate (10 mM) as substrate. Steviol inhibited p-aminohippuric acid uptake in rat renal cortical slices (Toskulkao et al. 1994b). Other metabolic effects

Clinical Factors Affecting Metabolic Rate And Oxygen Consumption

The cellular metabolic rate determines Vo2. The metabolic rate increases during physical activity, with shivering, hyperthermia and raised sympathetic drive (pain, anxiety). Similarly, certain drugs such as adrenaline4 and feeding regimens containing excessive glucose increase Vo2. Mechanical ventilation eliminates the metabolic cost of breathing which, although normally less than 5 of the total Vo2, may rise to 30 in the catabolic critically ill patient with respiratory distress. It allows the patient to be sedated, given analgesia and, if necessary, paralysed, further reducing Vo2.

Energy Metabolism

One early concept regarding the possible etiology of hepatic encephalopathy focused on a primary lack of cerebral energy as a result of hepatic metabolic failure.5 A variety of techniques have been used to suggest that hypometabolism may be linked to this condition. Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) scans have both demonstrated decreased cerebral glucose utilization in key regions of the brain.1 However, it remains to be demonstrated whether such observations represent primary or secondary changes, or play any role in the acute setting. Other studies have looked at high energy phosphate bonds utilizing cerebral 31P magnetic resonance spectroscopy and found no primary deficit in energy metabolism in such patients.47 A primary lack of metabolic energy per se now seems less likely than changes leading to failure of neurotransmission and secondary alterations of energy utilization.5

Metabolic Rate

The metabolism of the body simply means all the chemical reactions in all the cells of the body, and the metabolic rate is normally expressed in terms of the rate of heat liberation during chemical reactions. The Calorie. To discuss the metabolic rate of the body and related subjects intelligently, it is necessary to use some unit for expressing the quantity of energy released from the different foods or expended by the different functional processes of the body. Most often, the Calorie is the unit used for this purpose. It will be recalled that 1 calorie spelled with a small c and often called a gram calorie is the quantity of heat required to raise the temperature of 1 gram of water 1 C. The calorie is much too small a unit when referring to energy in the body. Consequently, the Calorie sometimes spelled with a capital C and often called a kilocalorie, which is equivalent to 1000 calories is the unit ordinarily used in discussing energy metabolism. Measurement of the Whole-Body...

Relating Genes to Inherited Traits

The normal gene encodes the Ob protein which functions in a signal pathway for the body to adjust its energy metabolism and fat accumulation (see Section 17.4). Mice carrying 2 mutant copies (ob ob) of the gene develop progressive obesity with increased efficiency in metabolism (i.e. increase weight gain per calorie intake). Mice with ob ob genotype apparently do not produce the gene product (Ob protein), because both copies of the ob gene are nonfunctional.

Fetal Origins Of Adult Disease

Despite the obvious dependence of fetal growth on the delivery of nutrients from the mother, it has been difficult to demonstrate simple relationships between maternal diet, energy or nutrient consumption, during pregnancy and the growth of the fetus. Although it has been possible to show relations between size at birth and the maternal intake of macronutrients, and selected micronutrients, the relative contribution to the variability in birth weight appears modest, explaining ofthe order of3 to 5 of the variability in birth weight22-24. This is similar to the 5 to 7 of variation in birth weight explained by smoking22. When characterising the nutritional status of an individual, the dietary intake is only one part, and body composition and the functional ability or the metabolic state of adaptation also have to be taken into consideration25. Thus, relative to the explanatory power of dietary consumption, maternal fat mass during pregnancy showed a much stronger relationship with the...

The Need For Dna Repair

Living organisms are constantly exposed to stress from environmental agents and from endogenous metabolic processes. An important factor is exposure to oxidative reagents or oxidative stress, largely arising as a side effect of mitochondrial energy metabolism. The resulting reactive oxygen species (ROS) attack proteins, lipids and DNA. Since proteins and lipids are readily degraded and resynthesized, the most significant consequence of oxida-tive stress is thought to be DNA modifications, which can become permanent via the formation of mutations and other types of genomic damage.

Alterations in Mitochondrial Function with Chronic Muscular Inactivity

More dependent on glycolytic pathways for ATP production during periods of muscle immobilization 77 . This shift in substrate utilization can be partially attributed to a decline in the expression of fatty acid transport proteins, resulting in a decreased import 90 and oxidation 77 of long-chain fatty acids into skeletal muscle. These changes are accompanied by an upregulation in the lactate dehydrogenase-A isoform, which promotes the conversion of pyruvate to lactate 91 . Therefore, chronic muscular inactivity has an impact on mitochondrial protein expression, which influences ATP provision and substrate utilization and muscle energy metabolism.

Neuroimaging of States of Consciousness

Metabolic rate of glucose in the resting state and during meditation. The only statistically significant difference (p 0.05) was the ratio of frontal versus occipital metabolic rates of glucose, with the increase of activity in frontal areas and reduction in primary and secondary visual centers during meditation. There were no changes in interhemispheric activity.

Hypertrophy of the Heart in Valvular and Congenital Heart Disease

Hypertrophy of cardiac muscle is one of the most important mechanisms by which the heart adapts to increased workloads, whether these loads are caused by increased pressure against which the heart muscle must contract or by increased cardiac output that must be pumped. Some physicians believe that the increased strength of contraction of the heart muscle causes the hypertrophy others believe that the increased metabolic rate of the muscle is the primary stimulus. Regardless of which of these is correct, one can calculate approximately how much hypertrophy will occur in each chamber of the heart by multiplying ventricular output by the pressure against which the ventricle must work, with emphasis on pressure. Thus, hypertrophy occurs in most types of valvular and congenital disease, sometimes causing heart weights as great as 800 grams instead of the normal 300 grams.

Summary And Recommendations For Exercise And Sports Performance

Although niacin has an important role in energy metabolism, few studies cite enhanced performance with administration of small amounts of niacin. Frankau8 used 40-50-mg doses of nicotinamide and reported improved performance in an agility test. Hilsendager and Karpovich9 showed no effect of 75 mg of niacin on a cycle or hand ergometer endurance test, and there certainly has been no research to show improved performance with doses of nicotinic acid large enough to impact cholesterol levels (3 g d is the typical dose).

Similarities and Differences Between DC and Ageing

An important feature of human ageing is increased risk of disease, such as cancer and a decrease in maintenance and function of almost all organs. Greying of hair is another obvious feature of the ageing population. In accordance with these, both DC patients and late generations of mTR knockout mice were observed to have increased incidence of malignancy and hair greying. The occurrence of cancer in these situations probably arises from chromosomal instability due to critically short telomeres (Counter et al. 1992, Dokal et al. 1992), whereas in ageing, additional factors also contribute to carcinogenesis. Such factors include free-radical-induced DNA damage, the accumulation of DNA mutations, changes in metabolic rate, and oxidative stress (Sohal et al. 2002, Frisard and Ravussin 2006). Another distinction between DC patients and the ageing population is the occurrence of hematological disorders. While hematological disorders are usually seen in DC patients and mTR knockout mice,...

Telomerase and Cancer

Fig. 5.5 Model of the pathogenesis of dykeratosis congenita and ageing. (A) X-linked DC and DKC1 gene mutation. (B) AD-DC and TERC gene mutation. (C) AD-DC and TERT gene mutation. (D) Ageing. Mutations in multiple components of the telomerase complex are identified in patients with dyskertatosis congenita, suggesting that excessive telomere shortening is the underlying cause of this disease. (A-C) The critically shortened telomeres lead to cell cycle arrest and or cell death in rapid dividing cells including stem cells and early progenitor cells. The cell senescence death results in the recruitment of more stem cells into cell cycle. Consequently, the increased proliferation of a decreased number of stem cells aggravates the rate of telomere shortening, which ends up with the depletion of the stem cells and the development of disease phenotype. Mutations in TERC or TERT directly reduce the enzymatic activity of telomerase and disrupt its function in telomere maintenance (B and C)....

Pool Formation in Classical Pathways

L2 and l4 form energy conjugates to each other representing the high- and low-energy occupancy in the system. l5 corresponds to l3 in example V. The incorporation and exchange of phosphate thus results in four different convex basis vectors, each representing different aspects of the complex role of phosphate in energy metabolism (e.g., high-energy phosphate and standalone inorganic phosphate, as shown here). Note that the phosphate in AP2 does not appear in the conservation of the elemental P, l3, since AP2 interacts as a whole moiety and is never reduced to other chemical moieties in this reaction network. In addition, the pool maps readily illustrate the reaction contributions to the conservation of biochemical moieties, such as shown by the pool map of l5 that involves only v4, v5, and v6.

Smaller Is More Practical

Organisms must have been very small in primordial soups And slow growers. Large cells would have to have complex systems including active transporters and moving apparatus. Small cells can rely on diffusion and Brownian movements for obtaining nutrients. Very slow metabolic rates would allow for use of minimal numbers of enzymes, since many of the reactions could be uncatalyzed, or catalyzed by metals and minerals or be contributed by nonspecificity of the existing enzymes. Such a system may well do the observed 10,000-fold slower biomass production than that of common bacteria. Nanobacteria have apparently small genomes. Hoescht 33258 staining indicated that nanobacteria should have DNA amounts between that of mycoplasmas and mitochondria. Can bacteria have novel nucleic acids contributing to smallness One potential example could be use of single stranded nucleic acid genome, maybe resembling the multi-copy single stranded DNA found in bacteria.

Imaging of Other Neurotransmitter Systems

Baxter LR, Jr, Schwartz JM, Mazziotta JC, et al. (1988). Cerebral glucose metabolic rates in nondepressed patients with obsessive-compulsive disorder. Am J Psychiatry 145 1560-1563. Baxter LR, Jr, Schwartz JM, Bergman KS, et al. (1992). Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder. Arch Gen Psychiatry 49 681-689. Benkelfat C, Nordahl TE, Semple WE, King AC, Murphy DL, Cohen RM (1990). Local cerebral glucose metabolic rates in obsessive-compulsive disorder. Patients treated with clomipramine. Arch Gen Psychiatry 47 840-848. Guich SM, Buchsbaum MS, Burgwald L, et al. (1989). Effect of attention on frontal distribution of delta activity and cerebral metabolic rate in schizophrenia. Schizophr Res 2 439-448. Nordahl TE, Benkelfat C, Semple WE, Gross M, King AC, Cohen RM (1989). Cerebral glucose metabolic rates in obsessive compulsive disorder. Neuropsychopharmacology 2 23-28. Schwartz JM, Stoessel PW, Baxter LR, Jr, Martin KM,...

Efferent Autonomic Pathways

Alpha-adrenergic receptors mediate sympathetically induced pupillary dilatation (mydriasis), vasoconstriction, and contraction of the vas deferens and bladder and rectal internal sphincters. Beta receptors mediate cardiac stimulation, vasodilation, bronchodilatation, relaxation of the bladder, and endocrine-metabolic effects. Muscarinic receptors mediate pupil constriction (miosis), salivary and lacrimal secretion, cardiac inhibition, bronchoconstriction, stimulation of motility and secretion in the gastrointestinal tract, evacuation of the bladder and rectum, and erection.

Other Transport Systems Responsible for Drug Transport at the Blood Brain Barrier

Although it has not been established whether the Na+-dependent hexose transporter SGLT is expressed at the BBB, a recent report suggested a participation of SGLT in the BBB transport of cycasin (58). Cycasin, methylazoxy-methanol-d-glucoside, is proposed to be a significant etiologic factor for the prototypical neurodegenerative disorder Western Pacific amyotrophic lateral sclerosis and for Parkinsonism-dementia complex. Cycasin is taken up into primary-cultured bovine BCECs in a dose-dependent manner with maximal uptake at a concentration of 10 M. Since cycasin uptake was significantly inhibited by a-methyl-d-glucoside, a specific analogue for the Na+-dependent glucose transporter, SGLT, as well as by phlorizin (a SGLT inhibitor), replacement of extracellular NaCl with LiCl, and dinitrophenol (an inhibitor of energy metabolism), cycasin is suggested to be transported across the BBB via a Na + energy-dependent SGLT (58).

Neurological Applications in Diagnosis and Treatment

Characteristic patterns of decreased regional glucose metabolism within the parietal and temporal lobes have been described in patients with AD.y In these patients there is a relative preservation of the calcarine fissure region, sensory motor region, cerebellum, and the basal ganglion region. Decreased metabolic rates for oxygen have also been reported in the same regions that demonstrate areas of decreased glucose metabolism in patients with Alzheimer's disease. Patients with progressive Parkinson's disease have a similar pattern, as seen in patients with Alzheimer's disease. Multiple-infarct dementia occurs after multiple lacunar infarctions. PET generally demonstrates multifocal regions of decreased glucose metabolism y that typically correlate to focal lesions demonstrated on CT scans and MR images. A significant decrease in glucose metabolism within the frontal and temporal lobes has been described in patients with Pick's disease. y Patients with...

Organisms with Low Biosynthetic Capacity

Those organisms that are most dependent upon their environment are the parasitic bacteria, the prototypical example of which are the mycoplasma. Interestingly, the complete genome of one species, Mycoplasma genitalium, was one of the first genomes to be sequenced (5). At 0.58 Mb, this represents the smallest known genome of any free-living organism. The genome contains 470 predicted protein coding regions, and these include those required for DNA replication, transcription and translation, DNA repair, cellular transport, and energy metabolism. However, comparisons with the genome (1.83 Mb, encoding 1,703 putative proteins) of another parasite, Haemophilus influenzae (6), led to the conclusion that the minimal gene set that is necessary and sufficient to sustain the existence of a modern-type cell is (only) 256 genes, or about half of the genome of M. genitalium (7). It should be noted, however, that while both of these parasitic organisms grow in the absence of their hosts, to do so...

Skeleton representation of the core metabolic pathways

A total of 80 extreme pathways were calculated 36 for the simplified metabolic system shown in Figure 13.18. Whether a pathway is accessible to the cell depends on (1) the regulatory network and (2) the environment in which the cell lives. Given the five inputs to the metabolic network and representing these inputs using Boolean logic (considering each as ON if present or OFF if absent), there are a total of 25 32 possible environments, which may be recognized by the cell.

Mitochondrial Enzyme Defects

Each tissue requires a different minimum level of mitochondrial adenosine triphosphate (ATP) production (a threshold) to sustain normal cell function. In a family with heteroplasmic mtDNA mutations, different family members can inherit different percentages of mutant mtDNAs and therefore present with different clinical symptoms. The phenotypical effect of the mutations depends on the severity of the damage to the protein the gene encodes. Cells with the lowest potential to replicate, like neurons, appear to be the ones most susceptible to degenerative changes in proteins, lipids, nuclear DNA, and mtDNA. Which neurons accumulate mtDNA mutations is proportional to the metabolic rate. Thus, cerebral cortex, which in positron emission tomography (PET) shows a high glucose utilization rate, and basal ganglia, which also have dopaminergic neurons that generate hydrogen peroxide and oxygen radicals, are the brain areas most susceptible to accumulation of...

Progressive Infantile Poliodystrophy Alpers Disease

Because there is no one pathognomonic clinical sign or laboratory study, Alpers' disease is a diagnosis of exclusion. Therefore, all rapidly progressive infantile encephalopathies need to be excluded by clinical story and or laboratory tests. Measurement of amino acids, organic acids, lactate, and pyruvate should be done in CSF as well as in blood. Mitochondrial biochemical and DNA studies should be performed, looking specifically for the MERRF mutation, as well as functional neuroimaging studies (i.e., MR spectrometry, single photon emission computed tomography SPECT , and PET if available), to garner evidence for defective energy metabolism and oxidative phosphorylation and to determine the biochemical geography. In Alpers' disease electroencephalograms (EEGs) are markedly abnormal, showing a diffuse encephalopathy. A characteristic electroencephalographic pattern consists of high-voltage, very slow delta waves mixed with low-voltage polyspikes. Serial visual evoked...

Myoclonic Epilepsy and Ragged Red Fibers Syndrome

The majority of cases of MERRF syndrome have a heteroplasmic G to A point mutation at bp8344 in the tRNALys gene.y This results in protein synthesis defects involving primarily complexes I and IV, which have the greatest number of mtDNA coded subunits. Any quantitative measure of energy metabolism--y P-NMR, anerobic threshold determination, or biochemical analysis of skeletal muscle--shows decreased ATP-generating capacity. When mutant mtDNAs exceed 85 percent in a tissue, the patient becomes symptomatic. Neuropathology shows degeneration of cerebellar cortex, substantia nigra, dentatorubral and pallidoluysian systems, locus ceruleus, inferior olivary nucleus, and pontine tegmentum.

Mitochondrial Encephalopathy Lactic Acidosis and Strokelike Episodes

About 80 percent of MELAS patients exhibit a heteroplasmic A to G point mutation in the dihydrouridine loop of the tRNA Leu(UUR) gene at mt3243.y Two other mutations in the same gene, at mt3250 and mt3271, have been identified in the remaining cases. Ihe MELAS3243 mutation alters the dihydrouridine loop of the tRNALeu(UUR) gene and changes a nucleotide at the binding site for a nuclear DNA encoded transcription termination factor. It is hypothesized that the mutation reduces the binding affinity of the transcription termination factor. Another possibility is that this mutation impairs protein synthesis by interfering with polypeptide chain elongation. Ihe cerebral infarcts are nonvascular, owing to transient dysfunction of oxidative phosphorylation within parenchyma. Areas of neuronal loss, demyelination, and astrocytic proliferation are found in the infarct-like brain areas. PET studies show reduced cerebral metabolic rates for oxygen but normal glucose utilization. Mitochondrial...

Leptin and Other Hormones

The leptin hormone receptor was discovered in 1997 when a mutant strain of extremely obese mice (lacking the gene to make leptin) were able to shed their weight when given leptin. With injections of leptin, the mice's appetite decreased while their metabolic rates increased. Although researchers wondered whether all obese people would lose weight on leptin, this did not occur. It turns out that, like the mutant obese mice, there are only a few rare cases known of human obesity caused by leptin deficiency. Most people seem to become obese by eating too much and being too sedentary. The leptin discovery should provide a successful treatment for rare cases of obesity in leptin-deficient individuals who, in the past, would not have been able to lose weight.

Metabolically Competent Cell Lines

One of the weakest elements within current in vitro gen-otoxicity screens is in the provision of an exogenous metabolizing system for the activation of pro-mutagens to DNA-reactive metabolites. First, such systems (usually rat liver S9 fraction with appropriate cofactors, see earlier) can be poor models for the likely human metabolism of a novel chemical. Second, they have the disadvantage that reactive metabolites formed exogenously may be unable to penetrate the cell membrane, or have short half-lives. The generation and detection of a genotoxic metabolite within the same cell therefore has obvious advantages. These problems may be alleviated by the introduction of human cDNAs expressing the appropriate metabolizing enzymes

Various Transporter Defects Hartnups Disease

Transporter (GLUT1) in brain microvessels at the blood- brain barrier, causing low CSF glucose (hypoglycorrhachia) and therefore decreased cerebral energy metabolism and brain function. GLUT1 is coded by a gene localized to chromosome 1 and is developmentally regulated, with the messenger RNA in brain increasing with increasing cerebral metabolic rate for glucose in infancy and childhood. Symptoms occur when this rate increases in early infancy, doubling or tripling that in the neonatal and fetal periods. This is a very rare condition, probably a spontaneous mutation, with patients being symptomatic heterozygotes. At about age 3 months, a perfectly normal infant develops seizures--myoclonic, atypical absences, or unclassifiable--that are refractory to antiepileptic drugs. Developmental delay occurs the longer seizures are uncontrolled and the diagnosis is undiscovered, which can culminate in mental retardation and secondary microcephaly. The differential diagnosis includes any disease...

Lifestyle Interventions

Up until now, we have primarily discussed interventions that have focused on the dietary or consumption end of weight regulation. As stated above, any effective weight loss program involves both regulating caloric intake and increasing caloric expenditure. Certainly, consideration of physical activity is critical for interventions aimed at losing weight as well as those aimed at lowering blood pressure. The primary method for increasing caloric expenditure is to increase the duration of time each day spent in activities that require more calories (exercise). Additionally, a regular physical exercise program prevents the reduction in metabolic rate that occurs with very low calorie dieting (Donahoe et al., 1984), enabling a dieter's body to burn off more calories. Therefore, a well-constructed exercise program involving both aerobic and muscle-strengthening exercises is an important part of calorie expenditure in successful weight loss programs. Let's examine the effect of increasing...

What to Eat After Treatment for Thyroid Disease

People who have had thyroid disease make the mistake of thinking they have to be on a special diet to maintain a healthy weight. Unless you're actively hypothyroid, thyrotoxic, or are preparing for a whole body scan (see Chapter 2), you are in the same boat as the rest of the population your metabolism will slow down with age, which will likely cause weight gain as you approach your forties and fifties, unless you compensate with more activity. Basically, eating healthy means you must distinguish between good fat and bad fat as well as good carbs and bad carbs.

Isolation of The Mouse Obese Gene

Obesity is one of the most common causes of serious health problems because it is often associated with type II diabetes (non-insulin dependent), hypertension, and hyperlipidemia. The mouse obsese (ob) gene which regulates energy metabolism, has been located and isolated from adipose tissues using linkage analysis, genetic mapping, and positional cloning (Zhang et al. 1994. Nature 372, 425-432.). The OB protein encoded by the normal gene acts on the central nervous system to effect a reduction of food intake and increase energy expenditure in mice, resulting in a balanced control of body fat tissues. Mice that are obese have a genotype of ob ob. Both copies of the gene are mutants.

Thyroid Metabolic Hormones

The thyroid gland, located immediately below the larynx on each side of and anterior to the trachea, is one of the largest of the endocrine glands, normally weighing 15 to 20 grams in adults. The thyroid secretes two major hormones, thyroxine and triiodothyronine, commonly called T4 and T3, respectively. Both of these hormones profoundly increase the metabolic rate of the body. Complete lack of thyroid secretion usually causes the basal metabolic rate to fall 40 to 50 per cent below normal, and extreme excesses of thyroid secretion can increase the basal metabolic rate to 60 to 100 per cent above normal. Thyroid secretion is controlled primarily by thyroid-stimulating hormone (TSH) secreted by the anterior pituitary gland.

Genome Streamlining Reductive Evolution

Genome reduction process was probably initiated very early in the evolution of Rickettsiales. By comparative genome analysis, Boussau et al. (23) reconstructed the evolutionary history of gene loss and gain process for a-proteobacterial genomes. Their estimate points out a massive reduction in the lineage from the a-proteobacterial ancestor (3000-5000 genes) to the last common ancestor of Rickettsiales (1000-2000 genes). Lost gene functions cover a wide spectrum of cellular activities including transport systems, energy metabolism, biosynthesis of small molecules, and DNA metabolism. A major loss of transcriptional regulators also appears to have occurred in the common ancestor of Rickettsiales, suggesting that most of their genes are likely constitutively expressed (12). The sole functional category that has been retained as mostly intact in Rickettsiales is that of genes involved in translation process.

Angina and myocardial infarction

Cardiac ischaemia is common in sleep, particularly during the second half of the night 7 . It is more often silent (asymptomatic) in sleep than during exercise. During sleep, cardiac output falls as a result of a slower heart rate rather than any change in stroke volume. In NREM sleep, blood pressure also falls and the drop in perfusing pressure reduces the coronary artery blood flow. An exaggeration of this hypotension (over-dipping), especially in stages 3 and 4 NREM sleep, may cause clinically significant cardiac ischaemia, especially in the presence of coronary artery disease. The peak time for myocardial infarction during NREM sleep is between 12.00 and 2.00 am when stages 3 and 4 are most likely. Despite this, NREM sleep is largely cardioprotective because of the low metabolic rate and the constant, but low, cardiac output.

Treatment of respiratory effects

Conventional pressure or volume present nasal ventilation increases the functional residual capacity and lung compliance by recruitment of alveoli through relief of pulmonary oedema. It also reduces ventilation-perfusion mismatching, but impairs venous return. It reduces the work of breathing and the metabolic rate so that there is less oxygen requirement and carbon dioxide elimination.

General Properties and Possible Metabolic Functions

Basis for Sports Nutrition Interest 1. Energy Metabolism Modification There is considerable evidence that dietary nickel influences carbohydrate and lipid metabolism in experimental animals. Some of the first studies suggesting that nickel may be essential showed that rats fed a 0.015-mg Ni kg diet compared with those fed a 20-mg Ni kg diet had depressed activities of enzymes that degrade glucose to pyruvate and enzymes that produce energy through the citric acid cycle these enzymes included glucose-6-phosphate dehydrogenase, isocitrate dehydrogenase and malate dehydrogenase.116 Also, glucose, glycogen and triglycerides were reduced in the liver, and ATP and glucose were reduced in serum of rats fed low dietary nickel.116 The amount of nickel fed to the supplemented controls was quite high relative to the suggested nickel requirement of rats of 0.15-0.2 mg kg diet.117 Because this high dietary concentration of nickel can affect iron metabolism in an apparent pharmacologic...

Opioids Ketamine and Benzodiazepines

Opioids are not thought generally to have neuroprotective properties but they do blunt stress-induced responses. Ketamine is an NMDA antagonist and has been shown to be protective in animal models of ischaemia.51 While the benzodiazepines decrease cerebral blood flow and cerebral metabolic rate, these effects are less impressive than with the intravenous anaesthetic agents. Despite occasional reports of neuroprotective benefit,52 these drugs are not generally thought to be useful neuroprotective agents.

Inhalation of Exogenous Carbon Monoxide

Some CO toxicity is accounted for by the fact that CO saturates hemoglobin and impairs its ability to transport oxygen. The affinity of CO to Hb is approximately 200 times higher than that to oxygen. During CO inhalation, the amount of CO bound to heme groups on the hemoglobin increases, generating carboxy-hemoglobin, which consequently decreases the amount of oxygen being carried to tissue and brain. Hypoxia is then likely to affect normal cellular function. The brain has a very high metabolic rate of O2 consumption, and impaired blood flow causes a rapid loss of consciousness. The brain has a complex array of mechanisms that limit damage following even the smallest changes in tissue oxygenation. During hypoxic states, ar-teriolar dilation occurs, improving O2 transport. In the case of CO hypoxia, changes in cerebral blood flow are strictly correlated to the amount of COHb. In addition, by binding on heme-containing proteins, such as the cytochrome system, CO is likely to impair...

Functional genomics and drug discovery

Could the focus on in vitro essential genes also lead to antibiotics that inhibit growth in liquid broth but do not eradicate bacterial infections The most optimistic answer to this question seems to be that we don't know. There are certainly genes, for example those encoding the core enzyme of RNA polymerase, that are always essential for bacterial growth. However, RNA profiling demonstrates that bacterial pathogens perceive liquid broth to be vastly different from the conditioned encountered in host cells and tissues. Even though these experiments do not monitor gene essentiality, they still suggest that not all in vitro essential genes are also essential in vivo. Carbon and energy metabolism of bacterial pathogens, for example, seems to be different in vivo and in liquid broth suggesting that genes necessary to grow with the narrow spectrum of carbon sources provided in vitro might not all be essential for growth in vivo. Very likely, this hypothesis will soon be tested by using...

A5 Rapprochement between the Mechanistic and Vital Materialist Approaches

West and Brown (2005) made the following comment during their review of a well-known puzzle in physiology (the allometric scaling of basal metabolic rate) 'Sciences typically cycle between periods of empiricism and theory, reductionism and holism. Empirical advances are . . . unified and synthesized by theoretical contributions. . . . Reductionist studies that discover components and processes at microscopic levels are given additional meaning by holistic studies that show how these phenomena contribute to the structure and function of large, complex systems at higher levels of organization. . . . Both are equally necessary for scientific progress'. This 'cycle' image seems to embrace science in general but in biomedical investigation, the mechanistic and vital-materialist approaches (loosely equivalent to 'reductionist' and 'holist') often appear to exclude rather than complement one another. At each turn of the 'typical cycle' the ideas and discoveries of the previous generation can...

Matrixrepresented protein networks genome maps

The resulting clustered map, shown in Figure 5b, reveals important characteristics of protein network connectivity and hierarchy. Many of the genes cluster into distinct modules, participating in related cellular functions 50 . Some of these modules correspond to protein pathways or complexes, while others contain genes that serve related cellular functions. Some of the functional modules are indicated in Figure 5b. Figure 5c depicts a zoomed-in region of the clustered map, indicated by the black square. Functional modules in this region correspond to genes involved in detoxification, polyketide synthesis, energy metabolism, and the degradation of fatty acids. This example illustrates how hierarchical clustering of genomic maps can enable the rapid identification of functional modules on a genome-wide basis 50 .

Thyroid Hormones Increase Active Transport of Ions Through

Activator Inhibitor

One of the enzymes that increases its activity in response to thyroid hormone is Na+-K+-ATPase. This in turn increases the rate of transport of both sodium and potassium ions through the cell membranes of some tissues. Because this process uses energy and increases the amount of heat produced in the body, it has been suggested that this might be one of the mechanisms by which thyroid hormone increases the body's metabolic rate. In fact, thyroid hormone also causes the cell membranes of most cells to become leaky to sodium ions, which further activates the sodium pump and further increases heat production. Stimulation of Fat Metabolism. Essentially all aspects of fat metabolism are also enhanced under the influence of thyroid hormone. In particular, lipids are mobilized rapidly from the fat tissue, which decreases the fat stores of the body to a greater extent than almost any other tissue element. This also increases the free fatty acid concentration in the plasma and...

Sympathetic Chemical Excitation of Heat Production As

Isolated measurements have shown that military personnel residing for several months in the arctic develop increased metabolic rates some Inuit (Eskimos) also have abnormally high basal metabolic rates. Further, the continuous stimulatory effect of cold on the thyroid gland may explain the much higher incidence of toxic thyroid goiters in people who live in cold climates than in those who live in warm climates.

Effect of Gut Activity and Metabolic Factors on Gastrointestinal Blood Flow

Gut Artery Supply

100 per cent therefore, the increased mucosal and gut wall metabolic rate during gut activity probably lowers the oxygen concentration enough to cause much of the vasodilation. The decrease in oxygen can also lead to as much as a fourfold increase of adenosine, a well-known vasodilator that could be responsible for much of the increased flow.

Thyroid Hormones Have Slow Onset and Long Duration of Action

After injection of a large quantity of thyroxine into a human being, essentially no effect on the metabolic rate can be discerned for 2 to 3 days, thereby demonstrating that there is a long latent period before thy-roxine activity begins. Once activity does begin, it increases progressively and reaches a maximum in 10 to 12 days, as shown in Figure 76-4. Thereafter, it decreases with a half-life of about 15 days. Some of the activity persists for as long as 6 weeks to 2 months.

Attention Deficit Hyperactivity Disorder

Positron emission tomography studies have reported reduced metabolic rates in, among other regions, the left anterior frontal area, where metabolism correlated inversely with measures of symptom severity (Zametkin et al., 1993). Functional MRI studies have reported abnormal activation of the striatum (Vaidya et al., 1998 Rubia et al., 1999), prefrontal cortex (Rubia et al., 1999), and anterior cingulate cortex (Bush et al., 1999). SPECT studies of ADHD adults have reported marked elevations of dopamine transporter levels in the basal ganglia (Dougherty et al., 1999 Krause et al., 2000), which, after a month of daily methylphenidate treatment, decreased to control levels (Krause et al., 2000). Additional findings in ADHD imaging studies include a smaller cerebellum (Castellanos and Tonnock, 2002), a region thought to be important in attentional processing (Middleton and Strick, 1994).

Factors Underlying Circadian Dependent Susceptibility To Light Induced Retinal Damage

It was also observed that removing glucose from the solution surrounding the retina, and thereby inhibiting energy metabolism, lead to a decrease in acid production and a reduction in the difference of pH between the retina and the surrounding solution.43 Inhibition of ATP utilization, through the inhibition of the Na+ K+ ATPase also reduced acid production. Therefore the observed change in pH levels was likely due to an increase in metabolism, and an increase in proton production at night. The observed change in pHo between night and day is not due to an increase in glycolysis over oxidative phosporylation, as both processes occur at the same proportion during the day and night.43 There is evidence that cellular acidification can initiate apoptosis. It has been shown that cellular acidification increases susceptibility of cells to heat damage.47 It has also been shown that neutrophils in tissue culture that undergo spontaneous apoptosis have an increase in acid production before the...

Insulin Glucagon and Diabetes Mellitus

Insulin and Its Metabolic Effects Insulin was first isolated from the pancreas in 1922 by Banting and Best, and almost overnight the outlook for the severely diabetic patient changed from one of rapid decline and death to that of a nearly normal person. Historically, insulin has been associated with blood sugar, and true enough, insulin has profound effects on carbohydrate metabolism. Yet it is abnormalities of fat metabolism, causing such conditions as acidosis and arteriosclerosis, that are the usual causes of death in diabetic patients. Also, in patients with prolonged diabetes, diminished ability to synthesize proteins leads to wasting of the tissues as well as many cellular functional disorders. Therefore, it is clear that insulin affects fat and protein metabolism almost as much as it does carbohydrate metabolism.

Function of Bile Salts in Fat Digestion and Absorption

The liver cells synthesize about 6 grams of bile salts daily. The precursor of the bile salts is cholesterol, which is either present in the diet or synthesized in the liver cells during the course of fat metabolism. The cholesterol is first converted to cholic acid or che-nodeoxycholic acid in about equal quantities. These acids in turn combine principally with glycine and to a lesser extent with taurine to form glyco- and tauro-conjugated bile acids. The salts of these acids, mainly sodium salts, are then secreted in the bile.

Regulation of Cortisol Secretion by Adrenocorticotropic Hormone from the Pituitary Gland

Adrenocorticotropic Hormone

Figure 77-6 shows the overall system for control of cortisol secretion. The key to this control is the excitation of the hypothalamus by different types of stress. Stress stimuli activate the entire system to cause rapid release of cortisol, and the cortisol in turn initiates a series of metabolic effects directed toward relieving the damaging nature of the stressful state.

Adrenocortical Hormones

The mineralocorticoids have gained this name because they especially affect the electrolytes (the minerals ) of the extracellular fluids-sodium and potassium, in particular. The glucocorticoids have gained their name because they exhibit important effects that increase blood glucose concentration. They have additional effects on both protein and fat metabolism that are equally as important to body function as their effects on carbohydrate metabolism.

Regulation of Energy Release from Triglycerides

Also important are several hormonal changes that take place to promote rapid fatty acid mobilization from adipose tissue. Among the most important of these is a marked decrease in pancreatic secretion of insulin caused by the absence of carbohydrates. This not only reduces the rate of glucose utilization by the tissues but also decreases fat storage, which further shifts the equilibrium in favor of fat metabolism in place of carbohydrates. Hormonal Regulation of Fat Utilization. At least seven of the hormones secreted by the endocrine glands have significant effects on fat utilization. Some important hormonal effects on fat metabolism in addition to insulin lack, discussed in the previous paragraph are noted here. Finally, thyroid hormone causes rapid mobilization of fat, which is believed to result indirectly from an increased overall rate of energy metabolism in all cells of the body under the influence of this hormone. The resulting reduction in acetyl-CoA and other intermediates...

Metabolic Functions of the Liver

The liver is a large, chemically reactant pool of cells that have a high rate of metabolism, sharing substrates and energy from one metabolic system to another, processing and synthesizing multiple substances that are transported to other areas of the body, and performing myriad other metabolic functions. For these reasons, a major share of the entire discipline of biochemistry is devoted to the metabolic reactions in the liver. But here, let us summarize those metabolic functions that are especially important in understanding the integrated physiology of the body. Fat Metabolism Although most cells of the body metabolize fat, certain aspects of fat metabolism occur mainly in the liver. Specific functions of the liver in fat metabolism, as summarized from Chapter 68, are the following

Nicotinic Acid And Substrate Availabilityperformance

Havel, Carlson, Ekelund and Holmgren37 investigated the effects of norepinephrine and nicotinic acid on energy metabolism in seven 21-26-year-olds. They ingested 1-3 g of nicotinic acid daily for 3 days before the testing to become accustomed to the flushing response caused by nicotinic acid, and then reported to the laboratory at 0800 h after a 12-15 h fast. During the entire procedure (just over 4 h) the participants were supine, with a catheter in an antecubital vein and a brachial artery, while expired air was collected intermittently. Norepinephrine was infused between minutes 45 and 60, and plasma concentrations of FFA, glycerol and glucose rose rapidly. At minute 120, nicotinic acid (100 or 200 mg) infusion started at 15 min intervals up to minute 225, when another infusion of norepinephrine started. The plasma concentration of FFA, glycerol and glucose decreased after the first infusion of nicotinic acid and stabilized in 30 min. The RER was increased after administration of...

Body Temperature Is Controlled by Balancing Heat Production Against Heat Loss

Heat production is a principal by-product of metabolism. In Chapter 72, which summarizes body energetics, we discuss the different factors that determine the rate of heat production, called the metabolic rate of the body. The most important of these factors are listed again here (1) basal rate of metabolism of all the cells of the body (2) extra rate of metabolism caused by muscle activity,

Respiratory Regulation of Acid Base Balance

If the rate of metabolic formation of CO2 increases, the Pco2 of the extracellular fluid is likewise increased. Conversely, a decreased metabolic rate lowers the Pco2. If the rate of pulmonary ventilation is increased, CO2 is blown off from the lungs, and the Pco2 in the extracellular fluid decreases. Therefore, changes in either pulmonary ventilation or the rate of CO2 formation by the tissues can change the extracellular fluid Pco2.

Primary Essential Hypertension

Cardiac output is increased due, in part, to the additional blood flow required for the extra adipose tissue. However, blood flow in the heart, kidneys, gastrointestinal tract, and skeletal muscle also increases with weight gain due to increased metabolic rate and growth of the organs and tissues in response to their increased metabolic demands. As the hypertension is sustained for many months and years, total peripheral vascular resistance may be increased.

Energy System Used In Various Sport Such As Phosphagen System Almist Entirely

Muscle Glycogen Replenishment

Recovery of the Muscle Metabolic Systems After Exercise. In Recovery of Muscle Glycogen. Recovery from exhaustive muscle glycogen depletion is not a simple matter. This often requires days, rather than the seconds, minutes, or hours required for recovery of the phosphagen and lactic acid metabolic systems. Figure 84-3 shows this recovery process under three conditions first, in people on a high-carbohydrate diet second, in people on a high-fat, high-protein diet and third, in people with no food. Note that on a high-carbohydrate diet, full recovery occurs in about 2 days. Conversely, people on a high-fat, high-protein diet or on no food at all show very little recovery even after as long as 5 days. The messages of this comparison are (1) that it is important for an athlete to have a high-carbohydrate diet before a grueling athletic event and (2) not to participate in exhaustive exercise during the 48 hours preceding the event. The changes that occur inside the hypertrophied muscle...

Liver Secretion of Cholesterol and Gallstone Formation

Cilia Respiratory Tract

Under abnormal conditions, the cholesterol may precipitate in the gallbladder, resulting in the formation of cholesterol gallstones, as shown in Figure 64-12. The amount of cholesterol in the bile is determined partly by the quantity of fat that the person eats, because liver cells synthesize cholesterol as one of the products of fat metabolism in the body. For this reason, people on a high-fat diet over a period of years are prone to the development of gallstones.

Effects of Cold and Other Neurogenic Stimuli on TRH and TSH Secretion One of the bestknown stimuli for increasing the

And therefore TSH secretion by the anterior pituitary gland, is exposure of an animal to cold. This effect almost certainly results from excitation of the hypo-thalamic centers for body temperature control. Exposure of rats for several weeks to severe cold increases the output of thyroid hormones sometimes to more than 100 per cent of normal and can increase the basal metabolic rate as much as 50 per cent. Indeed, persons moving to arctic regions have been known to develop basal metabolic rates 15 to 20 per cent above normal. Various emotional reactions can also affect the output of TRH and TSH and therefore indirectly affect the secretion of thyroid hormones. Excitement and anxiety conditions that greatly stimulate the sympathetic nervous system cause an acute decrease in secretion of TSH, perhaps because these states increase the metabolic rate and body heat and therefore exert an inverse effect on the heat control center.

Glucose Metabolism Disorders Hypoglycemia

Unlike other body tissues, the CNS relies almost exclusively on glucose as an energy substrate. CNS features that promote its vulnerability to hypoglycemia include its low glucose level (about 25 percent of the serum glucose value), its inability to store significant glucose as glycogen, and the high cerebral metabolic rate (5 mg 100 g brain tissue min) for glucose. yj Thus, for a 1400 g brain, the glucose requirement is 70 mg min. The brain's dependence on glucose, coupled with its limited glycogen stores, results in rapid CNS dysfunction when hypoglycemia occurs and permanent neurological

Effects Of Increased Intake Of Vitamins And Trace Minerals On Exercise Performance And Metabolism

Since the known roles of B vitamins emphasized cellular energy metabolism, it was only natural that B vitamins were studied for effects on physical performance. Previous scrutiny of human exercise performance trials after supplementation with one or more B complex vitamins has found apparent dose-response and time effects.35 For some vitamins (thiamin and pantothenate) more does seem to be better. Since some individual B vitamins will be covered in subsequent chapters, Table 1.1 lists the doses and results for combinations of B vitamins from several studies.23 30 36-44 Obviously, potential thresholds of effect for enhancement of physical performance by increased B complex vitamin intake are not clearly known and may not be consistent between populations, and multiple dose ranges have been studied in only a few experiments. Notice that there are no studies that have examined a full complement of all eight B vitamins and choline, and only two studies examined six B vitamins. Thus, every...

Cranial Nerve Dysfunction

The measurement of the CSF acid-base status is not normally part of the routine evaluation of this body fluid. In experimental studies, normal subjects have a CSF pH that is slightly lower than the pH of arterial blood and a pCO 2 that is higher. In contrast, bicarbonate levels are generally equal. Comparisons between CSF obtained through cisternal and lumbar punctures reveal that the pH is typically lower and pCO 2 higher in lumbar CSF. Again, bicarbonate levels are not significantly different. The variations between the cisternal and lumbar CSF samples may reflect differences in rates of local metabolism relative to clearance rates, y and the clinical measurement of the lumbar CSF pH may be an unreliable indicator of the metabolic state of the CNS.

Function of the Adrenal Medullae

A third difference between the actions of epineph-rine and norepinephrine relates to their effects on tissue metabolism. Epinephrine has 5 to 10 times as great a metabolic effect as norepinephrine. Indeed, the epinephrine secreted by the adrenal medullae can increase the metabolic rate of the whole body often to as much as 100 per cent above normal, in this way increasing the activity and excitability of the body. It also increases the rates of other metabolic activities, such as glycogenolysis in the liver and muscle, and glucose release into the blood. Another important value of the adrenal medullae is the capability of epinephrine and norepinephrine to stimulate structures of the body that are not innervated by direct sympathetic fibers. For instance, the metabolic rate of every cell of the body is increased by these hormones, especially by epinephrine, even though only a small proportion of all the cells in the body are innervated directly by sympathetic fibers.

Untreated Diabetes Mellitus And Respiratory Quotient

Now let us see how one can make use of the respiratory quotient to determine the relative utilization of different foods by the body. First, it will be recalled from Chapter 39 that the output of carbon dioxide by the lungs divided by the uptake of oxygen during the same period is called the respiratory exchange ratio. Over a period of 1 hour or more, the respiratory exchange ratio exactly equals the average respiratory quotient of the metabolic reactions throughout the body. If a person has a respiratory quotient of 1.0, he or she is metabolizing almost entirely carbohydrates, because the respiratory quotients for both fat and protein metabolism are considerably less than 1.0. Likewise, when the respiratory quotient is about 0.70, the body is metabolizing almost entirely fats, to the exclusion of carbohydrates and proteins. And, finally, if we ignore the normally small amount of protein metabolism, respiratory quotients between 0.70 and 1.0 describe the approximate ratios of...

Release of Energy from Glucose by the Pentose Phosphate Pathway

This pathway is especially important because it can provide energy independently of all the enzymes of the citric acid cycle and therefore is an alternative pathway for energy metabolism when certain enzymatic abnormalities occur in cells. It has a special capacity for providing energy to multiple cellular synthetic processes.

Functions Of Iodine

Individual tissues such as the central nervous system and maturation of the whole body, and also for energy production and oxygen consumption in cells, thereby maintaining the body's metabolic rate. The regulation of thyroid hormone synthesis, release and action is a complex process involving the thyroid, the pituitary, the brain and peripheral tissues.5 The hypothalamus regulates the plasma concentrations of the thyroid hormones by controlling the release from the pituitary of the thyroid-stimulating hormone (TSH) through a feedback mechanism related to the level of T4 in the blood. If blood T4 falls, the secretion of TSH is increased, which enhances both thyroid activities and the output of T4 into the circulation. This fine control of T4 secretion is essential, because either an excess or a deficit in the hormone will be detrimental to normal function. If the level of circulating T4 hormone is not maintained because of severe iodine deficiency, TSH remains elevated. Both of these...

Response of the Mothers Body to Pregnancy

As a consequence of the increased secretion of many hormones during pregnancy, including thyroxine, adrenocortical hormones, and the sex hormones, the basal metabolic rate of the pregnant woman increases about 15 per cent during the latter half of pregnancy. As a result, she frequently has sensations of becoming overheated. Also, owing to the extra load that she is carrying, greater amounts of energy than normal must be expended for muscle activity. Because of the increased basal metabolic rate of a pregnant woman and because of her greater size, the total amount of oxygen used by the mother shortly before

Study Design Dutch Pcb Dioxin Study

Apart from the effect ofearly exposure ofPCBs and dioxins on long term development, the effect of these pollutants on lactation performances was evaluated. Given the experimental evidence that several PCBs and their metabolites exert estrogenic effects and estrogens adversely influence maternal milk output and fat metabolism we investigated the relationship between maternal PCB body burden on the one hand, and the 24-h breast milk output, and triglyceride (TG) content of mature breast milk on the other.

Vitamin b6 in sports and exercise

As mentioned above, vitamin B6 (pyridoxine) has a number of functions related to energy metabolism and, thus, to exercise.16-20 First, vitamin B6 is required for the metabolism of proteins and amino acids. Pyridoxal 5' phosphate, the most biologically active form of vitamin B6, is a cofactor for transaminases, decarboxylases and other enzymes used in the metabolic transformations of amino acids and nitrogen-containing compounds.21 In addition, during exercise, gluconeogenesis involves the breakdown of amino acids, with the carbon skeleton being used for energy. Thus, the link between protein intake and vitamin B6 requirements is especially important for athletes, because active individuals typically have a higher protein requirement than sedentary individuals822 and higher protein intakes, due in part to their higher energy intakes. Another primary function of vitamin B6 related to physical activity is that PLP is required for glycogen phosphorylase, the key enzyme in the breakdown of...

Forearm Exercise Testing

Muscle fibers develop tension and shorten, thereby producing movement. These processes, including contraction and relaxation, are coordinated by the nervous system and are energy-requiring. Skeletal muscle meets its energy demands by converting chemical energy into mechanical energy. One feature unique to skeletal muscle, compared with other tissues, is the energy requirement difference between its resting and fully active states, a value that can approach two to three orders of magnitude.' 1 When the metabolic energy demands of active muscle cannot be met by the available energy sources, muscle fatigue and dysfunction occur. In such settings, when abnormalities of muscle biochemistry are responsible for the decreased energy supply, the term metabolic myopathies is applied. For diagnostic purposes, these disorders can be divided into two groups (1) exercise-induced (dynamic) myopathies, in which symptoms such as weakness, cramping, myalgias, and stiffness appear during exercise and...

Antisterility Vitamin In Human Beings

Thiamine operates in the metabolic systems of the body principally as thiamine pyrophosphate this compound functions as a cocarboxylase, operating mainly in conjunction with a protein decarboxylase for decarboxyla-tion of pyruvic acid and other a-keto acids, as discussed in Chapter 67. Thiamine Deficiency Causes Lesions of the Central and Peripheral Nervous Systems. The central nervous system normally depends almost entirely on the metabolism of carbohydrates for its energy. In thiamine deficiency, the utilization of glucose by nervous tissue may be decreased 50 to 60 per cent and is replaced by the utilization of ketone bodies derived from fat metabolism. The neuronal cells of the central nervous system frequently show chromatolysis and swelling during thiamine deficiency, changes that are characteristic of neuronal cells with poor nutrition. These changes can disrupt communication in many portions of the central nervous system. Deficiency of pantothenic acid in lower animals can...

Therapeutical Use of siRNA to Prevent and Treat Acute Liver Failure in Mice

Several molecular mechanisms can initiate liver cell injury and can further aggravate ongoing damage processes (23). Mitochondria are the prominent targets for hepatotoxicity of many drugs, leading to impairment of energy metabolism and intracellular oxidative stress. Once hepatocellular function is impaired, accumulation of hydrophobic bile acids causes additional cyto-toxicity. Although drug-induced hepatotoxicity appears to be mediated by both apoptosis and necrosis, viral infection predominantly induces cell death of hepatocytes by apoptosis. In contrast to necrosis, apoptosis is a highly conserved physiological process important in normal development and tissue homeostasis of multicellular organisms. Apoptosis occurs by two pathways a death receptor pathway and a mitochondrial pathway. Signals released from the cytoplasm and or from the cell membrane activate a well-characterized cascade of caspases (cysteine aspartase), which execute apoptotic cell death (24-27)....

Watersoluble Vitamins And Choline

Thiamin (vitamin B1) as a component of the coenzyme thiamin pyrophosphate (TPP), is important in energy metabolism. Thiamin is also needed for optimal neuromuscular functioning. Reportedly some athletes are marginally thiamin deficient. The need for thiamin is generally proportional to the caloric intake, especially when the diet is high in carbohydrates. Athletes may require more thiamin than sedentary individuals. Additional research is needed on the thiamin needs of physically active individuals. No UL exists for thiamin.7

Energy Output Affect

Normal basal metabolic rates at different ages for each sex. Fever Increases Metabolic Rate. Fever, regardless of its cause, increases the chemical reactions of the body by an average of about 120 per cent for every 10 C rise in temperature. This is discussed in more detail in Chapter 73. Sleep Decreases Metabolic Rate. The metabolic rate decreases 10 to 15 per cent below normal during sleep. This fall is due to two principal factors (1) decreased tone of the skeletal musculature during sleep and (2) decreased activity of the central nervous system. Malnutrition Decreases Metabolic Rate. Prolonged malnutrition can decrease the metabolic rate 20 to 30 per cent, presumably due to the paucity of food substances in the cells. In the final stages of many disease conditions, the inanition that accompanies the disease causes a marked decrease in metabolic rate, to the extent that the body temperature may fall several degrees shortly before death. The factor that most dramatically increases...

Physiological Basis of Sleep and Wakefulness

Several anabolic hormones, such as growth hormone, are secreted primarily during sleep, whereas catabolic hormones, such as cortisol, are produced mainly during wakefulness. The metabolic rate slows during NREM sleep, in which energy is conserved, the body temperature falls, and protein synthesis and other anabolic processes are accentuated. Reduced metabolic rate Anabolic Slightly reduced metabolic rate Metabolic rate The metabolic rate is reduced in NREM sleep by 5-10 . The core body temperature normally falls as NREM sleep is entered at the start of the night, and the control of sleep is closely related to thermoregulation. The reduced metabolic rate and vasodilatation of NREM sleep tend to reduce body temperature. The minute ventilation falls (1.23) and the arterial Pco2 rises by 2-3 mmHg. The stage of NREM sleep oscillates frequently at sleep onset and the threshold for carbon dioxide to act as a respiratory stimulus fluctuates correspondingly. This may lead either to frequent...

Systemic Chemotherapy

Glucocorticoids may result in CNS toxicity, as evidenced by both animal experiments and clinical observation. Rat studies demonstrate that glucocorti-coids disrupt the energy metabolism of neurons of the hippocampus, an important organ for memory processing, rendering them more vulnerable to toxic insults 47 . This finding is worrisome in the childhood cancer population because these patients are given steroids concurrently with other toxic agents 48 . Other experiments with rats have demonstrated the impairment of spatial learning in response to chronic corticosteroid treatment 49 .

Clinical Manifestations Of Mitochondrial Toxicity

Riboflavin (vitamin B2) is also important in mitochondrial energy metabolism it is converted to flavin mononucleotide and dinucleotide these flavins are coenzymes and necessary cofactors for the electron-transport chain. Thus, deficiency of either or both B vitamins can potentially play a role in NRTI-associated mitochondrial dysfunction, as previously suggested (62). The administration of such agents may potentially activate residual mitochondrial oxidative enzyme activity. These vitamins have been reported to be successful in the treatment of lactic acidosis (63-65), although no randomized studies

Effects Of Physical Performance

Due to riboflavin's involvement in many metabolic functions critical to exercise performance, its use as a performance enhancer has emerged. Specifically, riboflavin is involved in muscle cell energy metabolism. Recall that FAD and FMN are important in the metabolism of glucose, fatty acids, glycerol and amino acids for energy. When physical activity is performed, stress is put upon the biochemical pathways involved in the metabolism of these substrates.1228

Coordination of fetal growth endocrine versus paracrine

The signalling of both IGF2 and IGF1 is mediated by IGF1R, which is very similar in structure to the insulin receptor (INSR). Both IGF1R and INSR consist of two extracellular a subunits that bind the ligands, and two transmembrane P subunits that anchor the receptor in the membrane and contain tyrosine kinase activity in their cytoplasmic domains (LeRoith et al 1994). IGF1 binds to IGF1R with higher affinity than IGF2 (larger arrow). IGF2 binds to INSR invitro with an affinity 10 times lower than that of insulin (smaller arrow). The IGF2 INSR signalling interaction in vivo is supported by several gene knockouts (Efstratiadis 1998). An unknown placenta-specific receptor (X), which is distinct from IGF1R and INSR, mediates the IGF2 growth-promoting role in this organ (Efstratiadis 1998). Most of the IGF2 and IGF1 in the circulation and in the extracellular matrix are bound to IGF-binding proteins (IGFBPs). The IGF1R-mediated-pathways overlap extensively with INSR pathways....

Cardiovascular conditions

The metabolic rate and cardiac output fall during NREM sleep and the loss of sympathetic vasoconstriction reduces the systemic vascular resistance so that the blood pressure falls. NREM sleep is cardio-protective despite the drop in perfusion pressure. In contrast, in REM sleep autonomic control is unstable. Fluctuations in heart rate and blood pressure are common and the cerebral blood flow increases. These changes protect against some cardiovascular problems during sleep, but predispose to others.

Physiological effects

The peak melatonin secretion is reduced in primary insomnia in proportion to its duration rather than its severity. PET and SPECT scans have shown increased cerebral blood flow during sleep, with less reduction in the metabolic rate in the anterior cingulate and medial prefrontal cortex during wakefulness compared with NREM sleep.

The Normal Thyroid in Pregnancy

Normal, healthy pregnant women often develop symptoms and signs that suggest thyrotoxicosis or hyperthyroidism, such as a rapid pulse or palpitations, sweating, and heat intolerance because the metabolic rate increases during pregnancy. Despite this, hyperthyroidism occurs only in about one in a thousand pregnancies. Total thyroid hormone levels also increase during pregnancy because of the high levels of estrogen made by the ovaries. This estrogen causes an increase in a binding protein (thyroxine binding globulin, made by the liver and released into the blood) that carries thyroxine and releases it so it can enter the body's cells. The amount of the free thyroxine available to the tissues, however, is not increased, and the free T4 level is not affected (see Chapter 2). Many doctors mistakenly order total T4 levels and become alarmed, thinking that their pregnant patient has thyrotoxicosis. This can cause much anxiety and can be avoided if the doctor checks your TSH level and free...

Magnetic Resonance Imaging

Because MRI can be tuned to specific atoms, it can be utilized to examine the concentration of other biologically-active substances via a method known as magnetic resonance spectroscopy. This method is limited in that it provides only very gross information on the location of such substances within the brain (e.g., within the frontal lobe), and cannot be used unless the concentration of the substance is quite high. For example, it remains to be seen whether this method will be able to detect neurotransmitters. One substance examined using this technique is N-acetylaspartate (NAA), an amino acid found in high concentration within the nervous system. Reduced NAA is observed when neuronal functioning is less than optimal, such as occurs when pathological processes are acting upon neurons or when the energy metabolism of the brain is compromised. For example, lower levels of NAA in the dorsolateral prefrontal cortex of schizophrenics are associated with poorer cognitive abilities on a...

Resistance to Thyroid Hormone RTH or Thyroid Hormone Resistance

The story of resistance to thyroid hormone (RTH) started forty years ago with my (Ken) mentor, Dr. Samuel Refetoff. As an astute medical resident in a Los Angeles emergency room, he examined a six-year-old girl after she'd been in an automobile accident. This child had a goiter, bones that appeared to be those of a younger child (on x-ray exam), and was a deaf-mute. Such findings would typically make a physician suspect the child to have had severe hypothyroidism since birth however, Dr. Refetoff was surprised to find that the test for thyroid hormone showed nearly four times the normal level in this child. Some other member of this family had similar findings, although the basal metabolic rates (see Chapter 2) in all of the members were normal, suggesting that this elevated thyroid hormone level resulted in a normal thyroid hormone effect. This meant that the child was resistant to the effects of her thyroid hormone, requiring much more of it to do the same job as normal levels in...

Basic Understanding Of Mitochondria

Pyruvate Dehydrogenase Deficit

The most important and critical mitochondrial function is oxidative phos-phorylation, a mechanism by which the energy derived from metabolism of nutrients in the presence of oxygen is transformed into adenosine triphosphate (ATP). Figure 1 describes the mitochondrial oxidative energy metabolism. The system of oxidative phosphorylation includes five multienzyme complexes, designated as electron-transport chain complexes I through V. These enzymes are encoded by either mitochondrial or nuclear DNA (nDNA) (11). Therefore, a deficit of either mitochondrial or nDNA may lead to malfunction of oxidative phosphorylation. Mitochondrial DNA (mtDNA) is a double-stranded, circular molecule that encodes for 2 ribosomal RNAs, 22 transfers RNAs, and 13 polypeptides of complexes I, III, IV, and V of the respiratory chain. mtDNA

Pharmacological actions

Energy metabolism Effects on energy metabolism that do not involve mitochondria have been examined in cells lacking these organelles. Erythrocytes rely on glycolysis for ATP production. Stevioside has little effect on such cells (Kemmelmeier et al. cited in Kelmer Bracht, Kemmelmeier et al. 1985). The effect of stevioside on energy metabolism in isolated mitochondria has spurred the search for related effects on intact cells. At a concentration of 3 mM, however, stevioside was

Genetic Pathways of Postmitotic Cell and Organismal Survival

Mitochondria have been implicated in the aging process for several decades. Measuring the metabolic rates of several species during the 1920s, Pearl discovered the correlation between metabolic rate and life span animals with lower metabolic rates lived longer than animals with higher metabolic rates (Pearl 1928). Exceptions have been discovered since Pearl's initial observations, such as the high metabolic rates of some long-lived birds (Holmes et al. 2001) however Pearl's initial observation led to the formulation of the rate of living theory of aging. The theory suggests that reduced metabolic rates in an animal should result in an increased life span. Taken together, a clear correlation between metabolic activity and longevity cannot be derived from these studies. For example, clk-1 mutant animals are long-lived, but have normal respiratory rates, and RNAi of several ETC components results in increased longevity and decreased metabolic rates. Therefore, defining the role that...

Murphy Procedure Achilles Tendon

Brisement Procedure

Generally, Achilles tendon or gastrocnemius lengthening should be reserved for patients requiring significant foot reconstruction related to a tight gastroc-soleus complex, and for those needing to avoid forefoot ulceration such as diabetics. Diabetic patients benefit from Achilles tendon lengthening, probably due to their different metabolic state and altered configuration of collagen crosslinking, but can be susceptible to overlengthening. Perhaps, if these patients are athletic or are motivated to exercise to help control their diabetes, they could be studied for their altered biomechanics, and subsequent long-term benefits of the procedure.

Physiological Determinants of RCBF and RCBV

Increases in local neuronal activity are accompanied by increases in regional cerebral metabolic rate (rCMR). Until recently, the increases in rCBF and oxygen consumption produced during such functional activation were thought to be closely coupled to the cerebral metabolic rate of utilization of O2 (CMRO2) and glucose (CMRglu). However, it has now been clearly shown that increases in rCBF during functional activation tend to track glucose utilization but may be far in excess of the increase in oxygen consumption.19 This results in regional anaerobic glucose utilization and a consequent local decrease in oxygen extraction ratio and increase in local haemoglobin saturation. The resulting local decrease in deoxyhaemoglobin levels is used by functional MRI techniques to image the changes in rCBF produced by functional activation. Despite this revision of the proportionality between increased rCBF and CMRO2 during functional activation in the brain, the relationship between rCBF and...

Rays Ultrasounds and Other Diagnostic Pictures

CT scans are both useful and dangerous in evaluating people with thyroid cancer. They are useful because of their great sensitivity and their ability to look everywhere in the body. They can be coupled to PET scanners for something known as a fusion study that shows tumor sites in the body and characterizes each one by its metabolic rate of glucose consumption. On the other hand, the contrast dye that is injected into a person's veins when the CT scan is performed floods the entire body with nonradioactive iodine that can stay there for two to eleven months. This can result in a failure of radioactive iodine scans to detect tumor in the body and a failure of the radioactive

Simplistic Strategies by Nanobacteria

Nanobacteria may have low internal pressure. Normal bacteria concentrate metabolites inside them so that their internal pressures can be 3-5 bars. Such a system provides fast metabolism, but consumes energy and requires complex pumps and their controls. In unfavorable conditions cell death can result from inability to keep up the ion gradients. Nanobacteria may lack these systems. That might explain partially their high resistance to near-boiling temperatures (Bjorklund et al., 1998) known to explode bacteria mainly owing to an imbalance in intracellular ions. Their endurance is similar to that of some viruses.

Central Autonomic Network

The ventromedial nucleus is involved in energy metabolism and reproduction. In animals, ventromedial hypothalamic lesions result in obesity, which is associated with a decrease in sympathetic and an increase in parasympathetic nervous system activity. Finally, the lateral hypothalamic area participates in arousal, motivated motor behavior, and autonomic control and has widespread projections. The hypothalamic autonomic pathways descend predominantly ipsilaterally in the dorsomedial and ventrolateral tegmentum of the brain stem.

Physiology Aminostatic Theories

Membrane, 316, 316f Ferritin, 425, 425f, 862 Fertility, 1024-1025 Fertilization, 1000,1027-1029,1028f Fetal cells, in Parkinson's disease, 711 Fetus, 1042-1044. See also Neonate Newborn. calcium metabolism in, 1043,1043f circulation of, 1042, 1045, 1046f erythroblastosis of, 421f, 427, 454,1048 gastrointestinal tract of, 1043 growth of, 1042, 1043f iron metabolism in, 1043-1044, 1043f kidneys of, 1043 metabolism in, 1043 nervous system of, 1043 phosphate metabolism in, 1043,1043f red blood cells of, 1042 respiratory system of, 1042-1043 sex of, 1028 vitamins in, 1044 Fever, 898-900, 898f brain lesions and, 899 interleukin-1 in, 898-899 metabolic rate and, 887 rheumatic, 271 Fibrin, 459f, 460

Bone Remodeling

According to Wolffs law, bone has a cellular and molecular remodeling response to applied mechanical stress. The bony adaptation is a function of the number of loading cycles, cycle frequency, and the amount of strain, strain rate, and strain duration per cycle 13 . Both cortical and cancellous bone remodel continuously by osteoclastic and osteoblastic activity. This remodeling occurs throughout life and is affected by multiple factors including metabolic state, nutritional status, menstrual patterns, age, gender, level of fitness, and ethnicity. Bone also responds to piezoelectric changes, such that tensile forces create electropositivity and thereby stimulate osteoclastic activity 13 , whereas compressive forces create electronegativity and thereby stimulate osteoblastic activity. Most cortical stresses in nature are tensional. Torsion or twisting provides tension circumferentially, whereas bending produces tension on the convex side and compression on the concave side. Tensional...

Phylogeny Of Sleep

Mammals can also be short or long sleepers, much like humans. Although small and large animals have many similarities in terms of their sleep lengths and lengths of their sleep cycles, small animals have a higher metabolic rate, shorter life span, and increased relative sleep time compared to large animals with decreased metabolic rates (45). Larger animals have a longer REM-NREM cycle than smaller animals.

Weight Loss

Sometimes the increased bowel activity (hyperdefecation), combined with an increased metabolic rate, contributes to weight loss in spite of a healthy appetite. Overweight thyrotoxic people find this an unexpected bonus, but it is this single tendency that is responsible for a misunderstanding of thyroid and weight issues, and the misuse of thyroid hormone as a weight loss drug. Usually, weight loss is limited to ten to twenty pounds, and not all patients necessarily lose weight. Thyrotoxicosis often causes severe exhaustion, and some patients end up gaining weight because they become less active and their appetite is stimulated by their thyrotoxicosis. Unfortunately, some people with normal thyroid function take thyroid hormone pills to induce weight loss. This is a big mistake and can cause (among a host of other unpleasant side effects) heart trouble. Weight is discussed in more detail in Chapter 16.

Boost Your Metabolism and Burn Fat

Boost Your Metabolism and Burn Fat

Metabolism. There isn’t perhaps a more frequently used word in the weight loss (and weight gain) vocabulary than this. Indeed, it’s not uncommon to overhear people talking about their struggles or triumphs over the holiday bulge or love handles in terms of whether their metabolism is working, or not.

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