Regulatory Enzymes
We use the term regulatory enzymes[1] for enzymes of metabolic or signaling pathways that participate in their regulation. By regulation, we primarily mean stopping or starting such a track or influencing its speed. Regulatory enzymes are usually allosteric , stand at the beginning of the pathway , catalyze an irreversible reaction and are usually present in a small concentration . Like most enzymes, they can be affected at three levels[2]:
- catalytic activity of an enzyme ;
- amount of enzyme ;
- amount of substrate .
Regulation of enzyme activity[edit | edit source]
Two basic principles are used in the regulation of enzyme activity:
- binding of activators or inhibitors – a small molecule binds to the enzyme and changes its conformation, which affects the ability of the enzyme to bind the substrate or catalyze reactions. If that molecule is a product of a catalyzed reaction or a given metabolic pathway, we speak of a feedback mechanism . If it is a product of another metabolic pathway, we use the term cross regulation . An example of such regulation is the inhibition of glycolysis by citrate;
- covalent modification – the binding of phosphate to the hydroxyl of serine, threonine or tyrosine (phosphorylation) or, conversely, the loss of a phosphate group (dephosphorylation) changes the conformation of the enzyme. Simply put, enzymes of catabolic pathways are activated by phosphorylation and enzymes of anabolic pathways are deactivated[1].
Regulation of the amount of enzyme[edit | edit source]
This is regulation at the level of gene expression . It involves some hydrophilic hormones (via the MAP-kinase cascade), but mainly steroid hormones and thyroid hormones, which pass through the plasma membrane and have receptors in the cytoplasm or directly in the nucleus. Such regulation is more long-term, but begins with a certain latency.
Influence of gene expression by substrate – enzyme induction[edit | edit source]
Prolonged presence of an excess of substrate can induce an increase in the expression of genes for enzymes of the corresponding metabolic pathway. Ethanol thus induces the enzymes of its metabolism and induces tolerance. Similarly, some drugs induce the formation of detoxification enzymes (cyt P450), enzyme induction is also involved in drug interaction[2].
Amount of substrate[edit | edit source]
Many regulatory enzymes are primarily dependent on substrate availability (e.g. citrate synthase). In principle, the regulation of the pathway controlled by them is therefore shifted to the preceding enzyme (in this case, malate dehydrogenase and pyruvate synthase).
Compartmentation[edit | edit source]
Compartmentation, or the division of cells into separate units, is also involved in the regulation of various pathways in the human body. The transition of substances between them can be controlled and this also affects the pathways running in the given compartments.
