Lecture Connections 21 | Lipid Biosynthesis

Lecture Connections 21 | Lipid Biosynthesis © 2009 W H Freeman and Company CHAPTER 21 Lipid Biosynthesis Key topics: – Biosynthesis of fatty acids and eicosanoids – Biosynthesis of triacylglycerols – Biosynthesis of fatty cholesterol Lipids Fulfill a Variety of Biological Functions • • • • • • • • • Storage of energy Constituents of cellular membranes Anchors for membrane proteins Cofactors for enzymes Signaling molecules Pigments Detergents Transporters Antioxidants Catabolism and Anabolic of Fatty Acids Proceed via Different Pathways • Catabolism of fatty acids – produced acetyl-CoA – reducing power to NADH – location: mitochondria • Anabolism of fatty acids – requires malonyl-CoA and acetyl-CoA – reducing power from NADPH – location: cytosol in animals, chloroplast in plants Lipid Catabolism and Anabolism in Animal and Plant Cells Overview of Fatty Acid Synthesis • Fatty acids are built in several passes processing one acetate unit at a time • The acetate is coming from activated malonate in the form of malonyl-CoA • In each pass involves reduction of a carbonyl carbon to a methylene carbon Overview of Fatty Acid Synthesis Synthesis of Eicosanoids • Cyclooxygenase activity does not require metal cofactors • Cyclooxygenase is a target for many antiinflammatory drugs Biosynthesis of Cholesterol Formation of Mevalonate • HMG-CoA reductase is a target for some cardiovascular drugs Formation of Squalene • Pyrophosphate is a good leaving group in these nucleophilic substitution reactions Regulation of Cholesterol Biosynthesis • Insulin means “we have plenty of glucose” • Glucagon means “we are out of glucose” Chapter 21: Summary In this chapter, we learned that: • Malonyl-CoA is an important precursor for biosynthesis of fatty acids • Fatty acid synthesis is carried out by a large enzyme that contains multiple catalytic activities needed for the condensation, and subsequent reduction of acetate units • Not all organisms can synthesize polyunsaturated fatty acids; these that can utilize mixed function oxidases as desaturase • Cholesterol biosynthesis starts with synthesis of mevalonate from acetate; mevalonate yields two activated isoprenes; series of isoprene condensation steps gives squalene; oxidation and ring closure of squalene gives cholesterol ...CHAPTER 21 Lipid Biosynthesis Key topics: – Biosynthesis of fatty acids and eicosanoids – Biosynthesis of triacylglycerols – Biosynthesis of fatty cholesterol Lipids Fulfill a Variety... and acetyl-CoA – reducing power from NADPH – location: cytosol in animals, chloroplast in plants Lipid Catabolism and Anabolism in Animal and Plant Cells Overview of Fatty Acid Synthesis • Fatty