Enzyme Regulation and Hormonal Control in Metabolism

Three major types of enzyme regulation

1) Intrinsic control by metabolites (Allosterism/inhibitors), 2) Fast extrinsic control via hormones (Covalent modification, e.g., phosphorylation), 3) Slow extrinsic control via hormones (Gene expression)

Example of intrinsic enzyme regulation

Allosteric regulation or inhibition by metabolites

Adrenaline and glucagon regulation of enzymes

They promote phosphorylation via Protein Kinase A

Insulin regulation of enzymes

It promotes dephosphorylation

Enzymes activated in glycogen metabolism during hormonal regulation

Glycogen phosphorylase and Phosphorylase kinase

Enzyme inhibited in glycogen metabolism when phosphorylated

Glycogen synthase

Role of hormone-sensitive lipase

Breaks down triglycerides in lipid metabolism and is activated by phosphorylation

PFK-2/FBPase-2 enzyme regulation

Regulates levels of Fructose-2,6-bisphosphate, which affects glycolysis through PFK-1

Effect of phosphorylation on pyruvate dehydrogenase (PDH)

It becomes inactivated

Activation of AMPK

AMP binding and drugs like Metformin

Effect of AMPK activation

Phosphorylates multiple enzymes and transcription factors to regulate metabolism

Role of CREB in gene expression

Acts as a transcription factor activated by phosphorylation to regulate genes like PEP carboxykinase

Enzyme that cleaves fatty acids in muscle tissue

Lipoprotein lipase

Influence of vitamins B1 and B3 on metabolism

They act as cofactors; deficiencies lead to reduced enzyme activity (e.g., Beriberi, Pellagra)

Effect of caffeine on metabolism

Inhibits cAMP phosphodiesterase, increasing cAMP levels, thus enhancing PKA activity and promoting glycogenolysis and lipolysis