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

Chapter II. GENERAL PATTERNS OF METABOLISM

CHAPTER 9. BIOENERGETIC PROCESSES: ELECTRON TRANSPORT; OXIDATIVE PHOSPHORYLATION IN MITOCHONDRIA

9.2. ENZYMES OF BIOLOGICAL OXIDATION

1. Nicotinamide coenzyme-dependent dehydrogenases (NAD(P)-dependent dehydrogenases).

The Coenzymes of these dehydrogenases are NAD⁺ or NADP⁺ NUCLEOTIDES, whose molecular Structure contains a pyridine derivative — nicotinamide (Chapter 6).

The bond between NAD⁺ (or NADP⁺) and the protein moiety of the enzyme (apoenzyme) in pyridine-dependent dehydrogenases is unstable: it forms and breaks down during the catalytic cycle, which allows nicotinamide nucleotides to be considered substrates rather than prosthetic groups.

Reactions Catalyzed by NAD(P)-dependent dehydrogenases can be generally represented by the following equations:

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The active structure in the NAD⁺ or NADP⁺ molecule that accepts reducing equivalents from the substrate is the pyridine ring of nicotinamide. During the enzymatic reaction, the substrate abstracts two hydrogen atoms (2H⁺ + 2e^-), one of which in the form of a hydride ion: H^- (i.e., H⁺ + 2e^-) attaches to the pyridine ring of NAD(P)⁺, while the other, as a proton (H⁺ ion), enters the reaction medium:

As shown in the equation above, during the reaction, a hydrogen atom (i.e., H⁺ + e^-) attaches to the fourth carbon atom of nicotinamide, and the additional electron of the hydride ion interacts with the nitrogen of the pyridine ring. In the subsequent text, the reduced forms of nicotinamide coenzymes (NAD(P)H + H⁺ systems) will for simplicity be referred to in some cases simply as NAD(P)H.

Dehydrogenases dependent on nicotinamide coenzymes are widespread in living Cells. They function as anaerobic dehydrogenases that split off protons and electrons from numerous substrates, reducing NAD⁺ or NADP⁺, and subsequently transferring the reducing equivalents to other acceptors.

NAD-dependent dehydrogenases — these Enzymes catalyze oxidation-reduction reactions located on the oxidative pathways of METABOLISM — Glycolysis, The Citric Acid Cycle, fatty acid β-oxidation, Oxidative Deamination of Amino Acids, and the mitochondrial Respiratory Chain.

NADP-dependent dehydrogenases — these enzymes participate in reductive synthesis processes occurring in the Cytosol, specifically supplying hydrogen atoms for the synthesis of Fatty acids and Steroids. The main source of reduced NADP is the dehydrogenase Reactions of the Pentose Phosphate Pathway of glucose oxidation.

2. Flavin-dependent dehydrogenases.

Dehydrogenases of this type are chemically Flavoproteins, whose prosthetic groups include flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) (for structure, see Chapter 6).

Unlike pyridine-dependent dehydrogenases, in most flavin-dependent enzymes the coenzymes (FAD and FMN) are tightly bound to the protein moiety and do not dissociate from it at any stage of the catalytic cycle. An exception is FAD-dependent D-Amino Acid Oxidase, in which the protein has a low affinity for the coenzyme.

General equations for The oxidation of substrates involving flavin-dependent dehydrogenases:

The active part of the FAD or FMN molecule participating in the redox reaction is the isoalloxazine ring of riboflavin, which accepts two hydrogen atoms (2H⁺ + 2e^-) from the substrate:

In Biological Oxidation processes, certain flavoprotein enzymes play The Role of both anaerobic and aerobic dehydrogenases.

Flavoproteins as anaerobic dehydrogenases:

- NADH dehydrogenase — an FMN-dependent component of The inner mitochondrial membrane; it Functions as an electron collector, capturing electrons from NADH and transferring them to more electropositive Components of the mitochondrial respiratory chain;

- succinate dehydrogenase — an FAD-dependent Tricarboxylic Acid Cycle enzyme that oxidizes succinic acid;

- dihydrolipoyl dehydrogenase — an FAD-dependent enzyme involved in The oxidative decarboxylation of pyruvic acid;

- acyl-CoA dehydrogenase — an FAD-dependent enzyme of the fatty acid β-oxidation system;

- glycerol-3-phosphate dehydrogenase — an FAD-dependent enzyme that oxidizes glycerol-3-phosphate in Cell/35.html">Mitochondria.

Flavoproteins — aerobic dehydrogenases.

- L-amino acid dehydrogenase (oxidase) — an FMN-dependent Kidney enzyme specific for natural L-amino acids;

- xanthine oxidase (xanthine dehydrogenase) — an FAD-dependent enzyme that oxidizes Purines to uric acid;

- glucose oxidase — an FAD-dependent plant enzyme used for the Quantitative determination of glucose in biological fluids.

3. Cytochromes.

Cytochromes are iron-containing mitochondrial Proteins belonging to the class of Hemoproteins. In cytochromes, the iron ion is part of a metalloporphyrin complex (heme iron) that is structurally similar to the prosthetic groups of Hemoglobin and Myoglobin.

Due to the reversible valence change of heme iron, cytochromes function as electron carriers in biological oxidation chains in aerobic cells:

Depending on the Characteristic Features of their absorption spectra, cytochromes are divided into three main classes (a, b, c). Eukaryotic mitochondria contain five types of cytochromes — b, c, c₁, a, a₃; The Endoplasmic reticulum of hepatocytes contains cytochromes P-450 and b₅, which participate in oxidative hydroxylation reactions.