Amino Acid Catabolism

Glutamine/Glutamate and Asparagine/Aspartate Catabolism

Glutaminase is an important kidney tubule enzyme involved in converting glutamine (from liver and from other tissue) to glutamate and NH₃⁺, with the NH₃⁺ being excreted in the urine. Glutaminase activity is present in many other tissues as well, although its activity is not nearly as prominent as in the kidney. The glutamate produced from glutamine is converted to a-ketoglutarate, making glutamine a glucogenic amino acid.

Asparaginase is also widely distributed within the body, where it converts asparagine into ammonia and aspartate. Aspartate transaminates to oxaloacetate, which follows the gluconeogenic pathway to glucose.

Glutamate and aspartate are important in collecting and eliminating amino nitrogen via glutamine synthetase and the urea cycle, respectively. The catabolic path of the carbon skeletons involves simple 1-step aminotransferase reactions that directly produce net quantities of a TCA cycle intermediate. The glutamate dehydrogenase reaction operating in the direction of a-ketoglutarate production provides a second avenue leading from glutamate to gluconeogenesis.

Alanine Catabolism

Alanine is also important in intertissue nitrogen transport as part of the glucose-alanine cycle. Alanine's catabolic pathway involves a simple aminotransferase reaction that directly produces pyruvate. Generally pyruvate produced by this pathway will result in the formation of oxaloacetate, although when the energy charge of a cell is low the pyruvate will be oxidized to CO₂ and H₂O via the PDH complex and the TCA cycle. This makes alanine a glucogenic amino acid.

Arginine, Ornithine and Proline Catabolism

The catabolism of arginine begins within the context of the urea cycle. It is hydrolyzed to urea and ornithine by arginase.

Ornithine, in excess of urea cycle needs, is transaminated to form glutamate semialdehyde. Glutamate semialdehyde can serve as the precursor for proline biosynthesis as described above or it can be converted to glutamate.

Proline catabolism is a reversal of its synthesis process.

The glutamate semialdehyde generated from ornithine and proline catabolism is oxidized to glutamate by an ATP-independent glutamate semialdehyde dehydrogenase. The glutamate can then be converted to α-ketoglutarate in a transamination reaction. Thus arginine, ornithine and proline, are glucogenic.
 

Methionine Catabolism

The principal fates of the essential amino acid methionine are incorporation into polypeptide chains, and use in the production of α -ketobutyrate and cysteine via SAM as described above. The transulfuration reactions that produce cysteine from homocysteine and serine also produce α -ketobutyrate, the latter being converted to succinyl-CoA.

Regulation of the methionine metabolic pathway is based on the availability of methionine and cysteine

Phenylalanine and Tyrosine Catabolism

Phenylalanine normally has only two fates: incorporation into polypeptide chains, and production of tyrosine via the tetrahydrobiopterin-requiring phenylalanine hydroxylase. Thus, phenylalanine catabolism always follows the pathway of tyrosine catabolism. The main pathway for tyrosine degradation involves conversion to fumarate and acetoacetate, allowing phenylalanine and tyrosine to be classified as both glucogenic and ketogenic.

Tyrosine is equally important for protein biosynthesis as well as an intermediate in the biosynthesis of several physiologically important metabolites e.g. dopamine, norepinephrine and epinephrine

Vitamin B12: Cobalamin

Vitamin B12, also known as cobalamin, aids in the building of genetic material, production of normal red blood cells, and maintenance of the nervous system.

RDA The Recommended Dietary Allowance (RDA) for vitamin B12 is 2.4 mcg/day for adult males and females

Vitamin B12 Deficiency

Vitamin B12 deficiency most commonly affects strict vegetarians (those who eat no animal products), infants of vegan mothers, and the elderly. Symptoms of deficiency include anemia, fatigue, neurological disorders, and degeneration of nerves resulting in numbness and tingling.

The basic characteristics of enzymes includes

(i) Almost all the enzymes are proteins and they follow the physical and chemical reactions of proteins (ii) Enzymes are sensitive and labile to heat

(iii) Enzymes are water soluble

(iv) Enzymes could be precipitated by protein precipitating agents such as ammonium sulfate and trichloroacetic acid.

The Hemoglobin Buffer Systems

These buffer systems are involved in buffering CO₂ inside erythrocytes. The buffering capacity of hemoglobin depends on its oxygenation and deoxygenation. Inside the erythrocytes, CO₂ combines with H₂O to form carbonic acid (H₂CO₃) under the action of carbonic anhydrase.

At the blood pH 7.4, H₂CO₃ dissociates into H⁺ and HCO₃ ⁻ and needs immediate buffering.

VITAMINS

Based on solubility Vitamins are classified as either fat-soluble (lipid soluble) or water-soluble. Vitamins A, D, E and K are fat-soluble

Vitamin C and B is water soluble.

B-COMPLEX VITAMINS

Eight of the water-soluble vitamins are known as the vitamin B-complex group: thiamin (vitamin B1), riboflavin (vitamin B2), niacin (vitamin B3), vitamin B6 (pyridoxine), folate (folic acid), vitamin B12, biotin and pantothenic acid.

During fasting or carbohydrate starvation, oxaloacetate is depleted in liver because it is used for gluconeogenesis. This impedes entry of acetyl-CoA into Krebs cycle. Acetyl-CoA then is converted in liver mitochondria to ketone bodies, acetoacetate and b-hydroxybutyrate.

 Three enzymes are involved in synthesis of ketone bodies:

b-Ketothiolase. The final step of the b-oxidation pathway runs backwards, condensing 2 acetyl-CoA to produce acetoacetyl-CoA, with release of one CoA.

HMG-CoA Synthase catalyzes condensation of a third acetate moiety (from acetyl-CoA) with acetoacetyl-CoA to form hydroxymethylglutaryl-CoA (HMG-CoA).

HMG-CoA Lyase cleaves HMG-CoA to yield acetoacetate plus acetyl-CoA.

 b-Hydroxybutyrate Dehydrogenase catalyzes inter-conversion of the ketone bodies acetoacetate and b-hydroxybutyrate.

Ketone bodies are transported in the blood to other tissue cells, where they are converted back to acetyl-CoA for catabolism in Krebs cycle