The importance of irreversible reaction in metabolic regulation network.

In the metabolic pathway, the reactions catalyzed by various enzymes have different effects on the whole metabolic pathway. In irreversible reaction, the flow of metabolites is controlled by adjusting the activity and quantity of key enzymes. The whole metabolic pathway is unidirectional, and catabolism and anabolism in the body have their own pathways. This mechanism can make biosynthesis and degradation in thermodynamic state respectively. Biosynthesis is mostly energy-consuming reaction, often accompanied by ATP hydrolysis, while catabolism is mostly energy-releasing reaction.

The key enzymes in metabolic pathway have the following characteristics: 1. It catalyzes the slowest reaction, so it determines the total speed of the whole metabolic pathway. 2. Generally, it catalyzes one-way reaction, so its activity determines the direction of metabolic pathway. 3. Oligosaccharide is a key enzyme, and its activity is regulated by various forms; 4. The first enzyme of metabolic pathway and the first enzyme after branching are usually key enzymes.

In irreversible reactions, the regulation of key enzyme activities can be roughly divided into two ways: rapid regulation and slow regulation.

Delayed regulation mainly regulates the concentration of enzyme molecules in cells by changing the induction and repression of enzyme synthesis (affecting transcription and repression) or the speed of enzyme protein degradation and zymogen transformation. The induction and inhibition of enzymes can be explained by the operon model. Prokaryotic genes can form an operon as a synergistic unit of gene expression, which includes functionally related structural genes and control sites (promoters and operons) and can accept the role of regulating gene products (repressors). Such as the inducible operon lactose operon and the inhibitory operon trp operon.

Rapid regulation mainly changes the structure of enzyme molecules through * * valence modification (such as phosphorylation \ dephosphorylation), non * * valence effect of activator or inhibitor on enzyme (allosteric regulation), and polymerization and depolymerization of subunits. The regulatory effects of metabolic substrates and metabolites on the activities of key enzymes (allosteric enzymes) in the metabolic process are feedforward and feedback, respectively, which are either activation (positive effect) or inhibition (negative effect). ATP/ADP not only regulates metabolism as a cell energy state, but also is an allosteric effector of many key enzymes.

For example, three irreversible reactions of glycolysis are catalyzed by three key enzymes: 1, hexokinase; 2, hexokinase phosphate-1; 3. pyruvate kinase. The above three key enzymes are oligomerization enzymes and allosteric enzymes, which are mainly influenced by ATP/ADP(AMP) of intracellular energy. Hexokinase is the first enzyme in metabolic pathway, and glucose 6 phosphate is its allosteric inhibitor. Pyruvate kinase also regulates its activity in two ways: one is * * * valence modification: it loses its activity after phosphorylation; The other is polymerization and depolymerization (in the presence of activator, the equilibrium tends to form tetramer, and the activity increases, and the inhibitor can stabilize the conformation of dimer). The activation of pyruvate kinase by glucose 6- phosphate is positive feedback. In glycolytic pathway, ATP, as one of the final products, does not directly inhibit the first key enzyme, but first inhibits fructose phosphokinase, which will inevitably lead to the accumulation of glucose 6- phosphate. It inhibits hexokinase in feedback, which belongs to step feedback.

In fatty acid synthesis, high concentration of acetyl-coa inhibits the key enzyme acetyl-coa carboxylase, which is negative feedforward; The accumulation of fatty acids in the final product directly inhibits acetyl coenzyme A carboxylase.