Biochemistry and Molecular Biology - Belyasova N.A. 2002

Structure and Functions of Cellular Components
Cofactors
Carboxyl Group Carriers

Carboxylation-decarboxylation and transcarboxylation reactions are mediated by Enzymes, many of which require biotin as a cofactor. Biotin (vitamin H) serves as the prosthetic group of these enzymes and is covalently bound to their protein moiety via the ε-amino group of Lysine (Fig. 7.7). The heterocyclic core of the biotin molecule consists of imidazole (I) and thiophene (T) rings, whereas its side chain is represented by a valeric acid residue. The active form of the biotin cofactor is N⁵-carboxybiotin ("active carboxyl").

Biotin-containing enzymes are involved in carbon dioxide fixation, as well as The Biosynthesis of Lipids, Amino Acids, CARBOHYDRATES, Nucleic Acids, and Other Compounds. The primary role of biotin in these processes is to couple ATP Cleavage with carboxylation: in The First stage, bicarbonate (HCO₃^-) or CO₂ attaches to biotin to form carboxybiotin, a step that requires ATP Hydrolysis. In the second stage, carboxybiotin transfers the carboxyl group to the substrate, acting as a flexible "swinging arm" within the enzyme complex.

Only one biotin-containing enzyme is known that does not require ATP for catalysis—propionyl-CoA carboxylase (transcarboxylase) in propionic acid Bacteria. However, biotin still Functions as the carboxyl group carrier in this pathway as well.

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Fig. 7.7. Structure of biotin and "active carboxyl"

7.3. Acyl Group Carriers

An essential cofactor for acyl group transfer in Cells is coenzyme A (CoA). This compound serves as a coenzyme for at least 80 known acyl-transferring enzymes involved in The Tricarboxylic Acid Cycle, fatty acid β-oxidation, various Types of Fermentation, Carbohydrate METABOLISM, and numerous other vital processes.

The coenzyme A molecule contains vitamin B₃ (pantothenic acid) (Fig. 7.8), which is composed of pantoic acid and β-Alanine residues. The reactive site of coenzyme A is the sulfhydryl (-SH) group located at the terminus of a long, relatively flexible chain. Acyl residues are attached to this group via a thioester bond, forming derivatives known as acyl-CoA.

The simplest acyl derivative is acetyl-CoA (Fig. 7.8). This compound is characterized by a high acetyl-group transfer potential, which is confirmed by the large negative value of the Standard Free energy change (∆G^o) for the hydrolysis of acetyl-CoA:

Fig. 7.8. Structure of coenzyme A and its derivatives. The active sulfhydryl group is enclosed in the dashed outline

Ацетил-СоА + Н₂О ↔ Ацетат + СоА + Н⁺     ∆G° = -31,4 кДж/моль

Coenzyme A is a mobile cofactor that interacts with various enzymes during The transfer of acyl residues. In addition to CoA, cells contain another widespread cofactor that carries acyl residues, namely phosphopantetheine (Fig. 7.9). Phosphopantetheine is covalently linked (via a Serine residue) to the acyl carrier protein, which takes part in FATTY ACID BIOSYNTHESIS. Thus, this cofactor acts as a prosthetic group of Proteins, and its functions are analogous to those of CoA.

Bound phosphopantetheine has also been found in the citrate-cleavage enzyme and in enzymes involved in the synthesis of peptide Antibiotics.

Fig. 7.9. Structure of phosphopantetheine