Textbook - BIOLOGICAL CHEMISTRY - Gubsky Yu.I. - 2000

Chapter III. METABOLISM OF MAJOR CLASSES OF BIOMOLECULES

CHAPTER 18. AMINO ACID METABOLISM. II. SPECIALIZED METABOLIC PATHWAYS

18.1. METABOLIC PATHWAYS OF THE CARBON SKELETONS OF AMINO ACIDS. GLUCOGENIC AND KETOGENIC AMINO ACIDS

Twenty L-Amino Acids, differing in their chemical Structure, biological role, and metabolic features, are constituents of tissue Proteins and exist in free states within Cells and extracellular spaces. The carbon skeletons of free amino acids, formed via Transamination and deamination, are metabolites of Glycolysis, the citrate cycle, fatty acid β-oxidation, or substances capable of being converted into intermediates of these major Catabolic pathways in the body.

Class="center">Sites of amino acid oxidation in the citrate cycle

Due to the efficiency of biological METABOLISM, the specific biochemical catabolic Pathways of the twenty Natural Amino Acids converge to form only five molecular products—Biomolecules that enter The Tricarboxylic Acid Cycle and undergo complete oxidation to carbon dioxide and Water. These products are: acetyl-CoA, α-ketoglutarate, succinyl-CoA, fumarate, oxaloacetate (Fig. 18.1).

1. Acetyl-CoA is formed during the Catabolism of Ten amino acids, among which:

- Five amino acids (Alanine, Cysteine, Serine, Threonine, Glycine) are degraded to acetyl-CoA via Pyruvate;

- five amino acids (phenylalanine, Tyrosine, leucine, Lysine, Tryptophan) are degraded to acetyl-CoA via acetoacetyl-CoA.

Part of the carbon Skeleton of leucine and tryptophan, as well as isoleucine, is converted directly into acetyl-CoA; a portion of the isoleucine molecule is converted into succinyl-CoA.

2. α-Ketoglutarate is formed during the catabolism of five amino acids: glutamate, glutamine, Arginine, Histidine, and Proline.

Four of these amino acids enter the TCA cycle through their conversion into glutamate.

3. Succinyl-CoA is formed during the catabolism of Three amino acids: isoleucine, valine, and Methionine (a portion of the isoleucine molecule, as noted above, is converted into acetyl-CoA).

4. Fumarate is formed during the catabolism of Phenylalanine and Tyrosine; the carbon skeletons of these amino acids yield two TCA cycle metabolites—acetyl-CoA (via acetoacetyl-CoA) and fumarate.

5. Oxaloacetate is formed during the catabolism of aspartate and asparagine; aspartate is converted into oxaloacetate via a transamination reaction.

Fig. 18.1. Scheme of the incorporation of carbon skeletons of natural L-amino acids into The Citric Acid Cycle.

Glucogenic and ketogenic amino acids

Glucogenic amino acids

L-Amino acids metabolized in the tricarboxylic acid cycle (Fig. 18.1) can incorporate their carbon skeletons into glucose molecules. These amino acids, whose utilization in glucose synthesis occurs after their entry into the TCA cycle via acetyl-CoA, α-ketoglutarate, succinyl-CoA, and fumarate, are termed glucogenic amino acids.

Ketogenic amino acids

Two L-amino acids enter catabolism solely via acetoacetyl-CoA, which can be converted in Liver cells into the Ketone Bodies acetoacetate and β-hydroxybutyrate. These are ketogenic amino acids. Some amino acids contribute their carbon fragments to The formation of both glucose and ketone bodies (Table 18.1).

Table 18.1. Glucogenic and ketogenic amino acids

Ketogenesis from amino acids is of particular negative significance in certain enzymatic disorders, notably in uncompensated Diabetes Mellitus; therefore, patients with this condition are advised to limit their Dietary intake of ketogenic amino acids.

Fat-like and Nonfat-like Amino Acids

Depending on the specific pathways of their conversion, L-Amino acids are also subdivided into nonfat-like and fat-like.

Nonfat-like amino acids are those that degrade via Carbohydrate Catabolism pathways. These include histidine and nonessential amino acids, with the exception of tyrosine. All amino acids in this group are glycogenic.

Fat-like amino acids are those whose conversion involves intermediates shared with the Fatty acid oxidation pathways. This group includes tyrosine and Essential Amino Acids, with the exception of histidine. Some of these amino acids are glycogenic, some are ketogenic, and others are both glyco- and ketogenic.

Amino acids as Precursors of Other Biomolecules

The Biological Significance of amino acids extends beyond their role in the synthesis of body proteins. Free amino acids serve as precursors for the formation of numerous compounds with specialized Functions, such as NUCLEOTIDES, Coenzymes, Porphyrins, Vitamins, Hormones, Neurotransmitters, and other structural and regulatory biomolecules.

Due to The complexity of the individual metabolic pathways involving the carbon skeletons of most natural amino acids, the following Discussion will focus solely on the metabolic features and the involvement in the synthesis of physiologically active compounds of acyclic and cyclic L-amino acids of the greatest Biomedical Importance.