Medicalbiochemistry

Page 109

Acetyl CoA + 7 malonyl CoA + 14NADPHH = Palmitoyl CoA + 7CoA +7CO2 +14 NADP +7H2O. The main sources of NADPH for fatty acid synthesis are the pentose shunt but the malic enzyme reaction has also a small contribution. The formation of malonyl CoA is the committed step in fatty acid synthesis For the synthesis, all the enzymes are required in the form of fatty acid Synthase complex. Stochiometry of the reaction Acetyl CoA + 7malonyl CoA + 14NADPH + 7H+ → Palmitate + 7CO2 + 14NADP+ + 8CoA + 6H2O

Hence the overall stoichiometry for the synthesis is: 8Acetyl CoA + 7ATP + 14NADPH → Palmitate + 14NADP+ + 8CoA + 6H2O + 7ADP + 7Pi

Regulation o Fatty Acid Synthesis: •

High carbohydrate diet increases synthesis.

Palmitoyl CoA inhibits synthesis

Fasting decreases acetyl carboxylase, decreases fatty acid synthesis.

Insulin stimulates fatty acid synthesis.

Biosynthesis of Triacylglycerols 1. Major pathway: 2.Activate fatty acids are attached to glycerophosphate to form phosphatidic acid ,by acyl transferase.It is converted to diglyceride by the removal of phosphate group by phosphatase.Another fatty acid is attached to the diglyceride to form triglyceride.The synthesis takes place in adipose tissue and Liver. 2. Minor pathway: Monoglyceride is acylated to form diglyceride .It is later converted to triglyceride by addition of one more fatty acid.The process is seen during absorption of Lipids.

Biosynthesis of Cholesterol Cholesterol is synthesized in the cell cytosol and endoplasmic reticulum from acetylCoA. Liver and intestine account each for 10% of the total cholesterol synthesized in the body. Almost all tissues containing nucleated cells can synthesize cholesterol. The synthesis follows five major steps which include: •

Acetyl CoA is converted to HMG CoA.

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