BIOCHEMISTRY - Textbook - Ostapchenko L. I. - 2012

Chapter 6. AMINO ACID METABOLISM AND FUNCTIONS. PROTEIN BIOSYNTHESIS

6.6. Pathways of Amino Acid Non-Nitrogenous Residue Metabolism

During Amino Acid Catabolism, the amino group is cleaved off with the release of ammonia. Another product of AMINO ACID DEAMINATION is a non-nitrogenous residue in the form of α-keto acids. Amino acid catabolism occurs almost continuously. Under normal conditions, approximately 100 g of Amino Acids are degraded daily in The Human Body, and the same amount must be supplied via dietary Proteins.

Most of the non-nitrogenous amino acid residues are converted into Pyruvate either directly (Ala, Ser) or through a more complex pathway, initially transforming into one of the TCA cycle metabolites. Subsequently, Reactions of the citrate cycle produce oxaloacetate, which is converted into phosphoenolpyruvate. Pyruvate kinase then converts phosphoenolpyruvate into pyruvate. Pyruvate undergoes oxidative decarboxylation, turning into acetyl-CoA, which is oxidized in the TCA cycle to CO₂ and H₂O with energy release. This conversion pathway is typical mainly for dietary amino acids.

In cases of glucose deficiency in the body, phosphoenolpyruvate is channeled into Gluconeogenesis. This pathway occurs during starvation, prolonged physical exertion, Diabetes Mellitus, and other severe chronic diseases accompanied by The breakdown of the body's own proteins. The rate of gluconeogenesis from amino acids is regulated by Hormones. For instance, Glucagon increases The activity of the process's regulatory Enzymes, whereas cortisol induces the synthesis of gluconeogenic enzymes in the Liver. Activation of gluconeogenesis from amino acids also occurs on a predominantly protein-rich diet.

Catabolism of all amino acids yields six products that enter the common catabolic pathway: pyruvate, acetyl-CoA, α-ketoglutarate, succinyl-CoA, fumarate, and oxaloacetate (Fig. 6.22).

Amino acids that are converted into pyruvate and TCA cycle intermediates (α-KG, succinyl-CoA, fumarate) and ultimately yield oxaloacetate can also be utilized in gluconeogenesis. Such amino acids belong to the group of glycogenic amino acids.

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Fig. 6.22. Incorporation of Amino acid non-nitrogenous residues into the common catabolic pathway: 1–5, anaplerotic reactions

Certain amino acids that are converted into acetoacetate (Lys, Leu) or acetyl-CoA (Leu) during catabolism and can be utilized in the synthesis of Ketone Bodies are termed ketogenic.

A number of amino acids are used for the synthesis of both glucose and ketone bodies, because their catabolism yields two products: a specific citrate cycle metabolite and either acetoacetate (Trp, Phe, Tyr) or acetyl-CoA (Ile). Such amino acids are called mixed or glycoketogenic amino acids (Fig. 6.22, Table 6.5).

Non-nitrogenous amino acid residues are used to replenish the pool of common catabolic pathway metabolites consumed in the synthesis of BIOLOGICALLY ACTIVE SUBSTANCES. These reactions are called anaplerotic. Five anaplerotic reactions are highlighted in Fig. 6.22:

The enzyme pyruvate carboxylase (with biotin as a coenzyme), which catalyzes this reaction, is found in The Liver and Muscles.

2) amino acid → glutamate → α-ketoglutarate

This conversion takes place in many Tissues under the action of Glutamate dehydrogenase or aminotransferases.

3)

Propionyl-CoA and subsequently succinyl-CoA can also be formed As a result of the Breakdown of Higher Fatty acids with an odd number of carbon atoms.

4) amino acid → fumarate

5) amino acid → oxaloacetate

Reactions 2 and 3 occur in all tissues (except the liver and muscles) that lack pyruvate carboxylase, whereas reactions 4 and 5 take place mainly in the liver. Reactions 1 and 3 (Fig. 6.22) are the primary anaplerotic reactions.

Table 6.5

Classification of amino acids According to the fate of their non-nitrogenous residue