Human Biochemistry, Volume 1 - Murray R. 1993

Structure and Functions of Proteins and Enzymes
Enzymes: General Properties
Coenzymes

Many Enzymes exert a catalytic effect on substrates only in the presence of a specific, heat-stable, low-molecular-weight organic compound known as a coenzyme. In such cases, the holoenzyme (the catalytically active complex) consists of an apoenzyme (the protein moiety) and an associated coenzyme. The coenzyme may be bound to the apoenzyme by covalent or noncovalent bonds. The term "prosthetic group" refers specifically to a covalently bound coenzyme. Reactions requiring coenzymes include oxidation-reduction reactions, group-transfer and isomerization reactions, as well as Condensation reactions (classes 1, 2, 5, and 6 According to the IUB system). Cleavage reactions, such as hydrolytic Reactions Catalyzed by digestive enzymes, proceed in the absence of a coenzyme (classes 3 and 4 under the IUB system).

Coenzymes as Second Substrates

A coenzyme can be viewed as a second substrate, or cosubstrate, for two reasons. First, during the course of the reaction, the coenzyme undergoes chemical alterations that are the exact counterpart of those occurring in the primary substrate. For instance, in oxidation-reduction dehydrogenase reactions, the substrate molecule is oxidized while the coenzyme molecule is reduced (Fig. 7.1).

Similarly, in Transamination reactions, Pyridoxal phosphate acts as a second substrate in two coupled reactions, serving as an amino group carrier between various a-amino and a-keto acids.

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Fig. 7.1. Example of an oxidation-reduction reaction in which NAD⁺ acts as a cosubstrate.

The second reason why a coenzyme can be considered an equal participant in the reaction is that its involvement may hold fundamental physiological significance. For example, Muscle contraction under anaerobic conditions is accompanied by The conversion of Pyruvate to lactate. However, neither lactate nor pyruvate is the primary focus here; the ultimate purpose of the reaction is to convert NADH back into NAD⁺. In the absence of NAD⁺, Glycolysis cannot continue, and anaerobic ATP synthesis—and consequently Muscle Function—comes to a halt. The reduction of pyruvate to lactate under anaerobic conditions ensures The oxidation of NADH to NAD⁺, which is essential for ATP synthesis. Other reactions can also fulfill this NAD⁺-regenerating function. The Significance of this process becomes particularly clear when we look beyond animals to Other forms of life. In Bacteria and Yeasts growing anaerobically, the substances derived from pyruvate serve as oxidizing agents for NADH while themselves becoming reduced (Table 7.1).

Table 7.1. Systems for the anaerobic regeneration of NAD⁺

The Role of Coenzymes as Group Carriers in Intermediary METABOLISM

Biochemical transfer reactions can be represented as follows:

D—G + А ⇄ A—G + D.

Here, the functional group G is transferred from the donor molecule, D—G, to the acceptor molecule A. In this context, the coenzyme may function either as a terminal acceptor (in hydrogen-removal reactions) or as an intermediate carrier (in transamination reactions). This latter function can be illustrated as follows:

Although this scheme depicts only a single complex (CoE—G), multiple such intermediate complexes may participate.

When the transferred group is a hydrogen atom, it is customary to denote only the left-hand half-reaction:

Hydrogen-transfer reactions occurring in living Cells (Table 7.1) follow the scheme

Coenzymes can be classified as follows:

Coenzymes involved in The transfer of groups other than hydrogen atoms:

Sugar phosphates

CoASH

Thiamine pyrophosphate

Pyridoxal phosphate

Folate coenzymes

Biotin

Cobamide (B₁₂) coenzymes

Lipoic Acid

Coenzymes involved in hydrogen atom transfer:

NAD/NADP⁺

FMN, FAD

Lipoic acid

Coenzyme Q

Coenzymes derived from B-group Vitamins and AMP

B-group vitamins are integral components of many coenzymes. For instance, enzymes involved in Amino acid metabolism require coenzymes derived from vitamin B₆. B-group vitamins—nicotinamide, thiamine, riboflavin, and pantothenic acid—serve as components of coenzymes participating in biological Oxidation and reduction processes, whereas Coenzyme forms of Folic acid and cobamide are involved in the transfer of single-carbon units.

A structural component of many coenzymes is the adenine ring linked to D-ribose and inorganic phosphate. Consequently, these coenzymes can be regarded as derivatives of adenosine monophosphate (AMP) (see Table 34.1). The structural formulas of NAD⁺ and NADP⁺ are shown in Fig. 7.2.