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Essentially all urea formed in the human body is synthesized in the liver. In the absence of the liver or in serious liver disease, ammonia accumulates in the blood. This is extremely toxic, especially to the brain, often leading to a state called hepatic coma.

The stages in the formation of urea are essentially the following:

After its formation, the urea diffuses from the liver cells into the body fluids and is excreted by the kidneys.

Oxidation of Deaminated Amino Acids. Once amino acids have been deaminated, the resulting keto acids can, in most instances, be oxidized to release energy for metabolic purposes. This usually involves two successive processes: (1) the keto acid is changed into an appropriate chemical substance that can enter the citric acid cycle, and (2) this substance is degraded by the cycle and used for energy in the same manner that acetyl coenzyme A (acetyl-CoA) derived from carbohydrate and lipid metabolism is used, as explained in Chapters 67 and 68. In general, the amount of adenosine triphosphate (ATP) formed for each gram of protein that is oxidized is slightly less than that formed for each gram of glucose oxidized.

Gluconeogenesis and Ketogenesis. Certain deaminated amino acids are similar to the substrates normally used by the cells, mainly the liver cells, to synthesize glucose or fatty acids. For instance, deaminated alanine is pyruvic acid. This can be converted into either glucose or glycogen. Alternatively, it can be converted into acetyl-CoA, which can then be polymerized into fatty acids. Also, two molecules of acetyl-CoA can condense to form acetoacetic acid, which is one of the ketone bodies, as explained in Chapter 68.

The conversion of amino acids into glucose or glyco-gen is called gluconeogenesis, and the conversion of amino acids into keto acids or fatty acids is called keto-genesis. Of the 20 deaminated amino acids, 18 have chemical structures that allow them to be converted into glucose, and 19 of them can be converted into fatty acids.

Obligatory Degradation of Proteins

When a person eats no proteins, a certain proportion of body proteins is degraded into amino acids and then deaminated and oxidized. This involves 20 to 30 grams of protein each day, which is called the obligatory loss of proteins. Therefore, to prevent net loss of protein from the body, one must ingest a minimum of 20 to 30 grams of protein each day; to be on the safe side, a minimum of 60 to 75 grams is usually recommended.

The ratios of the different amino acids in the dietary protein must be about the same as the ratios in the body tissues if the entire dietary protein is to be fully usable to form new proteins in the tissues. If one particular type of essential amino acid is low in concentration, the others become unusable because cells synthesize either whole proteins or none at all, as explained in Chapter 3 in relation to protein synthesis. The unusable amino acids are deaminated and oxidized. A protein that has a ratio of amino acids different from that of the average body protein is called a partial protein or incomplete protein, and such a protein is less valuable for nutrition than is a complete protein.

Effect of Starvation on Protein Degradation. Except for the 20

to 30 grams of obligatory protein degradation each day, the body uses almost entirely carbohydrates or fats for energy, as long as they are available. However, after several weeks of starvation, when the quantities of stored carbohydrates and fats begin to run out, the amino acids of the blood are rapidly deaminated and oxidized for energy. From this point on, the proteins of the tissues degrade rapidly—as much as 125 grams daily—and, as a result, cellular functions deteriorate precipitously. Because carbohydrate and fat utilization for energy normally occurs in preference to protein utilization, carbohydrates and fats are called protein sparers.

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