FATTY ACID SYNTHESIS (1).pdf by doctor naveeda

Fatty acid synthesis

1. FATTY ACID
SYNTHESIS
DR NAVEEDA ZAIGHAM

2. •Carbohydrates and proteins in excess of body needs
are converted into fatty acids
•In liver, lactating mammary glands and adipose tissue
•Process is endergonic and reductive
•Substrates are Acetyl Co A , NADPH and ATP

5. Acetyl Co A Carboxylation To Malonyl Co A
•Carbon to carbon condensation takes place by
carboxylation and then decarboxylation of acyl groups
•Carboxylation is catalyzed by Acetyl Co A carboxylase
•Coenzyme is Biotin

6. Short Term Regulation
•Carboxylation is rate limiting and regulated step
•Inactive form of ACC is a protomer
•Allosterically activated by Citrate which causes
polymerization of protomers
•Allosterically inhibited by by Malonyl Co A which causes
depolymerization

8. Short Term Regulation
•Reversible phosphorylation is also regulating
•Adenosine monophosphate –activated protein kinase
AMPK phosphorylates and inactivates ACC
•AMPK is activated Allosterically by AMP and covalently
by phosphorylation via kinases

10. Short Term Regulation
•AMPK Kinase is activated by cAMP dependent PKA
•Counter regulatory hormones Glucagon and
Epinephrine phosphorylates and inactivates ACC
•Insulin dephosphorylates and activates ACC

11. Long Term Regulation
•Prolonged consumption of diet containing excess calories
especially high carb, low fat diet increases ACC synthesis
•Low calorie, high fat, low carb diet has opposite effect
•Transcription factor ChREBP upregulates Fatty acid
synthesis

12. Long Term Regulation
•Insulin up regulates via SREBP-1c
•Fatty acid synthase is similarly regulated
•Metformin used in treatment of type 2 diabetes mellitus
lowers plasma TAG through activation of AMPK and
inhibits ACC and FAS expression

13. Long Term Regulation
•Metformin lowers blood glucose by increasing AMPK-
mediated glucose uptake by muscles