7.5Basic Metabolic Response
To examine some of the typical enzymatic reaction patterns involved in basic metabolic pathways (Fig. 7-3), here we discuss the generation (phosphorylation) and degradation (dephosphorylation) of phosphoester bonds, the generation and cutting of C-C bonds and dehydrogenation reactions.
Phosphorylation Reaction (Kinase)
Phosphoester bonds are formed when the phosphate group at the terminal (γ-position) of ATP is transferred to the OH group of a substrate. Phosphofructokinase reaction is an example of this. Many biological materials such as sugars are metabolized in a phosphorylated form.
Fructose 6-phosphate + ATP → Fructose 1,6-bisphosphate + ADP
Dephosphorylation Reaction (Phosphatase)
The hydrolysis reactions of phosphoester bonds include the following:
■ Fructose 1,6-bisphosphtase reaction
Fructose 1,6-bisphosphate + H2O → Fructose 6-phosphate + Phosphate
Formation and Cleaving Reactions of C-C Bonds
Reactions that form or cut carbon-carbon bonds are the most important reactions for the synthesis and degradation of biological molecules; since hydrocarbon chains are stable, the process can be achieved using carbonyl compounds instead. Its basic principle is similar to that of an organic chemical reaction known as aldol condensation, and is based on the carbonyl carbon obtaining a positive charge and the hydrogen bonded to the carbon next to the carbonyl group being dissociated, becoming a negative ion (a carbanion), between which a condensation reaction occurs.
Below are some examples of such reactions.
■ Aldolase reaction
Glyceraldehyde 3-phosphate + Dihydroxyacetone phosphate ⇄ Fructose 1,6-bisphosphate
Dehydrogenation is a reaction in which NAD+ or NADP+ receives two hydrogen atoms from organic compounds and is reduced, and the organic compounds are then oxidized. Specifically, during the process of organic compounds being gradually oxidized and losing free energy in the living body, reducing capacity is stored in the form of NADH and NADPH. Dehydrogenation often accompanies decarboxylation. In this case, the carbon dioxide generated is immediately eliminated from the reaction system, which induces an irreversible reaction in the normal direction, resulting in large negative ∆G˚’ values. Pyruvate dehydrogenase reaction is an example of this:
Pyruvic acid + CoASH + NAD+ → Acetyl-CoA + NADH + H+ + CO2
∆G˚’ = - 33.5 kJ/mol
In this reaction, thiamin pyrophosphate (TPP) - a derivative of vitamin B1 - and lipoic acid function as a prosthetic group. A hydroxyethyl group first attaches to the TPP, and is then passed to the oxidized lipoic acid and converted to an acetyl group, which is further passed to CoA. This reaction is very similar to that of 2-oxoglutaric acid dehydrogenase.