Amino acids metabolism

Amino acids metabolism

Over view
Quantitatively, proteins are the most important group of endogenous macromolecules. A person weighing 70 kg contains about 10 kg protein, with most of it located in muscle. By comparison, the proportion made up by other
Nitrogen containing compounds is minor. The organism’s nitrogen balance is therefore primarily determined by protein metabolism. Several hormones—mainly testosterone+ and cortisol- regulate the nitrogen balance .In adults, the nitrogen balance is generally in equilibrium—i. e., the quantities of protein nitrogen taken in and excreted per day are approximately equal. If only some of the nitrogen
taken in is excreted again, then the balance is positive. This is the case during growth, for example. Negative balances are rare and usually occur due to disease. Proteins taken up in food are initially broken down in the gastrointestinal tract into amino acids, which are resorbed and distributed in the organism via the blood The human body is not capable of synthesizing 10 of the 20 proteinogenic amino acids it requires . These amino acids are essential, and have to be supplied from food .

Proteins are constantly being lost via the intestine and, to a lesser extent, via the kidneys. To balance these inevitable losses, at least 30 g of protein have to be taken up with food every day. Although this minimum value is barely reached in some countries, in the industrial nations the protein content of food is usually much higher than necessary. As it is not possible to store amino acids, up to 100 g of excess amino acids per day are used for biosynthesis or degraded in the liver in this situation. The nitrogen from this excess is converted into urea and excreted in the urine in this form. The carbon skeletons are used to synthesize carbohydrates or lipids ,or are used to form ATP. It is thought that adults break down 300–400 g of protein per day into amino acids (proteolysis). On the other hand, approximately the same amount of amino acids is reincorporated into proteins (protein biosynthesis). The body’s high level of protein turnover is due to the fact that many proteins are relatively short-lived. On average, their half-lives amount to 2–8 days. The key enzymes of the intermediary metabolism have even shorter half-lives. They are sometimes broken down only a few hours after being synthesized, and are replaced by new molecules. This constant process of synthesis and degradation makes it possible for the cells to quickly adjust the quantities, and therefore the activity, of important enzymes in order to meet current requirements. By contrast, structural proteins such as the histones, hemoglobin, and the components of the cytoskeleton are particularly long-lived.
Almost all cells are capable of carrying out biosynthesis of proteins .
However, the functional forms of most proteins arise only after a series of additional steps. To begin with, supported by auxiliary proteins, the biologically active conformation of the peptide chain has to be formed. During subsequent “post-translational” maturation, many proteins remove part of the peptide chain again and attach additional groups— e. g., oligosaccharides or lipids. These processes take place in the endoplasmic reticulum and in the Golgi apparatus .Finally, the proteins have to be transported to their site of action .

REMOVAL AND EXCRETION OF AMINO GROUPS

Excess nitrogen is eliminated from the body in the urine. The kidney adds small
quantities of ammonium ion to the urine in part to regulate acid-base balance, but nitrogen is also eliminated in this process. Most excess nitrogen is converted to urea in the liver and goes through the blood to the kidney, where it is eliminated in urine.
Amino groups released by deamination reactions form ammonium ion (NH4+), which must not escape into the peripheral blood. An elevated concentration of
ammonium ion in the blood, hyperammonemia, has toxic effects in the brain (cerebral edema, convulsions, coma, and death). Most tissues add excess nitrogen to the blood as glutamine by attaching ammonia to the Ɣ-carboxyl group of glutamate. Muscle sends nitrogen to the liver as alanine and smaller quantities of other amino acids, in addition to glutamine. Figure below summarizes the flow of nitrogen from tissues to either the liver or kidney for excretion.

Glutamine Synthetase

Most tissues, including muscle, have glutamine synthetase, which captures excess nitrogen by aminating glutamate to form glutamine. The reaction is irreversible.Glutamine, a relatively nontoxic substance, is the major carrier of excess nitrogen from tissues.


Glutaminase
The kidney contains glutaminase, allowing it to deaminate glutamine arriving in
the blood and to eliminate the amino group as ammonium ion in urine. The reaction is irreversible. Kidney glutaminase is induced by chronic acidosis, in which excretion of ammonium may become the major defense mechanism. The liver has only small quantities of glutaminase; however, levels of the enzyme are high in the intestine where the ammonium ion from deamination can be sent directly to the liver via the portal blood and used for urea synthesis. The intestinal bacteria and glutamine from dietary protein contribute to the intestinal ammonia entering the portal blood.

Aminotransferases (Transaminases}

Both muscle and liver have aminotransferases, which, unlike deaminases, do not
release the amino groups as free ammonium ion. This class of enzymes transfers the amino group from one carbon skeleton (an amino acid) to another (usually