Metabolism Of Amino Acids

Proteins are the most abundant organic compounds and constitute a major part of the body dry weight (10-12 kg in adults). They perform a wide variety of static (structural) and dynamic (enzymes, hormones, clotting factors, receptors etc.) functions. About half of the body protein (predominantly collagen) is present in the supportive tissue (skeleton and connective) while the other half is intracellular. 

Proteins are nitrogen-containing macro- molecules consisting of L--amino acids as the repeating units. Of the 20 amino acids found in proteins, half can be synthesized by the body (non-essential) while the rest have to be provided in the diet (essential amino acids).

The proteins on degradation (proteolysis) release individual amino acids. Amino acids are not just the structural components of proteins. Each one of the 20 naturally occurring amino acids undergoes its own metabolism and performs specific functions. Some of the amino acids also serve as precursors for the synthesis of many biologically important compounds (e.g. melanin, serotonin, creatine, etc.). Certain amino acids may directly act as neurotransmitters (e.g. glycine aspartate, and glutamate). Protein metabolism is more appropriately learned as the metabolism of amino acids.

AMINO ACID POOL

An adult has about 100 g of free amino acids which represent the amino acid pool of the body. The amino acid pool may be an oversimplification of the facts, since there is no single compartment—rather, several compart- ments exist.

Glutamate and glutamine together constitute about 50%, and essential amino acids about 10% of the body pool (100 g). The concentration of intracellular amino acids is always higher than the extracellular amino acids. Amino acids enter the cells against a concentration gradient by active transport.

The amino acid pool of the body is maintained by the sources that contribute (input) and the metabolic pathways that utilize (output) the amino acids

1. Sources of amino acid pool

Turnover of body protein, intake of dietary protein and the synthesis of non-essential amino acids contribute to the body amino acid pool.

(a) Protein turnover: The protein present in the body is in a dynamic state. It is estimated that about 300-400 g of protein per day is constantly degraded and synthesized which represents body protein turnover. There is a wide variation in the turnover of individual proteins. For instance, the plasma proteins and digestive enzymes are rapidly degraded, their half-lives being in hours or days. The structural proteins (e.g. collagen) have long half-lives, often in months and years.

Control of protein turnover: The turnover of the protein is influenced by many factors. A small polypeptide called ubiquitin (mol. wt. 8,500) tags with the proteins and facilitates degradation. Certain proteins with amino acid sequence proline, glutamine (one letter code E), serine and threonine (PEST sequence) are rapidly degraded.


(b) Dietary protein: There is a regular loss of nitrogen from the body due to degradation of amino acids. In healthy adults, it is estimated that about 30-50 g of protein is lost everyday from the body. This amount of protein (30-50 g/ day) must, therefore, be supplied daily in the diet to maintain nitrogen balance. The purpose of dietary protein is to supply amino acids (particularly the essential ones) for the synthesis of proteins and other nitrogen compounds.

There is no storage form of amino acids as is the case for carbohydrates (glycogen) and lipids (triacylglycerols). The excess intake of amino acids is metabolized—oxidized to provide energy, converted to glucose or fat. The amino groups are lost as urea and excreted. The protein consumption in developed countries is much higher than the recommended dietary allowance (i.e. 1g/kg body weight/day). The daily protein intake by an adult in most countries is 40-100 g. Protein is digested by proteolytic enzymes to amino acids which are absorbed in the intestine and enter the body pool of amino acids.


(c) Synthesis of non-essential amino acids: Ten out of the 20 naturally occurring amino acids can be synthesized by the body which contribute to the amino acid pool.

2. Utilization of amino acids from body pool

(a) Most of the body proteins (300-400 g/day) degraded are synthesized from the amino acid pool. These include enzymes, hormones, immunoproteins, contractile proteins etc.

(b) Many important nitrogenous compounds (porphyrins, purines, pyrimidines, etc.) are produced from the amino acids. About 30 g of protein is daily utilized for this purpose.

(c) Generally, about 10-15% of body energy requirements are met from the amino acids.

(d) The amino acids are converted to carbohydrates and fats. This becomes predominant when the protein consumption is in excess of the body requirements.

METABOLISM OF AMINO ACIDS —GENERAL ASPECTS

The amino acids undergo certain common reactions like transamination followed by deamination for the liberation of ammonia. The amino group of the amino acids is utilized for the formation of urea which is an excretory end product of protein metabolism. The carbon skeleton of the amino acids is first converted to keto acids (by transamination) which meet one or more of the following fates.

1. Utilized to generate energy.

2. Used for the synthesis of glucose.

3. Diverted for the formation of fat or ketone bodies.

4. Involved in the production of non-essential amino acids.

TRANSAMINATION

The transfer of an amino ( NH2) group from an amino acid to a keto acid is known as transamination. This process involves the interconversion of a pair of amino acids and a pair of keto acids, catalysed by a group of enzymes called transaminases (recently, aminotransferases).

DEAMINATION

The removal of amino group from the amino acids as NH3 is deamination. Transamination (discussed above) involves only the shuffling of amino groups among the amino acids. On the other hand, deamination results in the liberation of ammonia for urea synthesis. Simultaneously, the carbon skeleton of amino acids is converted to keto acids. Deamination may be either oxidative or non-oxidative.

Although transamination and deamination are separately discussed, they occur simultaneously, often involving glutamate as the central molecule. For this reason, some authors use the term transdeamination while describing the reactions of transamination and deamination, particularly involving glutamate.