Regulatory Mechanisms- Lipid Metabolism

Enzyme	Pathway	Effect of substrate concentration	Allosteric Modification/ Fed back Inhibition	Induction/ Repression	Clinical Significance
Acetyl co A Carboxylase	Fatty acid synthesis	Activity increases during well fed state Activity decrease during fasting	Activator- Citrate, ATP Acetyl co A Insulin-by causing de phosphorylation by stimulating protein phosphatase Inhibitors- Long chain fatty acids, Epinephrine, Glucagon- via changes in phosphorylation state through c AMP mediated phosphorylation cascade	Induced byInsulin Repressed byGlucagon	Activity decreases in diabetes Mellitus
Carnitine Acyl Transferase	Carnitine shuttle	Activity low in fed state, high during fasting	Activated byGlucagon through lipolysis and provision of fatty acids for oxidation Inhibited by insulin and malonyl co A		Inherited CAT-I deficiencyaffects only the liver, resulting in reduced fatty acid oxidation and ketogenesis, with hypoglycemia.
HMG co A Reductase	Cholesterol synthesis	Activity low in fasting state,	Activated by Insulin, Thyroid hormone Inhibited by –Glucagon, Glucocorticoids,(By reversible phosphorylation) Dietary cholesterol (Hepatic synthesis) Mevalonate and cholesterol ,the products of pathway	Expression of HMG COA reductase is regulated by sterol regulatory element binding protein Also induced by Insulin	Activity high in Diabetes mellitus die to availability of excess Acetyl co A. Activity inhibited by Statins used as cholesterol lowering drugs.

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