Kramers BIOCHEM Study Lipid Metabolism 8/26/10 1.

What is (including substrates, enzyme(s) and cofactors) the sequence of events for the cytoplasmic synthesis of fatty acids? 2. What are the feed back inhibitors and activators of synthesis of fatty acids? 3. What is the role of citrate, NADPH and acetyl CoA in fatty acid synthesis. 4. How do triacylglycerides get synthesized? 5. What happens after TAGs are synthesized? 6. What is the enzyme LPSs role? 7. What are the regulatory factors of Fatty Acid and TAG synthesis? 8. Describe the role of adipose tissue in energy production and storage. 9. What are regulatory/ hormones factors that involve FA/TAGs synthesis What is (including substrates, enzyme(s) and cofactors) the sequence of events for the cytoplasmic synthesis of fatty acids? i. Synthesis of Acetyl CoA a. Made in Mitochondria from PDH (after pyruvate enters from glycolysis) b. PC makes OAA which combines with Acetyl CoA and makes citrate c. Citrate leaves mitochondria and citrate lyase makes OAA and Acetyle CoA (used in FA sythesis) ii.Conversion of Acetyl CoA to Malonyl CoA a. Catalyze by ACC (acetyl CoA Carboxylase) this with ATP and CO2 converts it to Malonyl CoA iii. Elongation of FA a. Adding of Malonyl CoA- (two carbons to add onto chain) in Fatty Acid Synthase Complex b. After each addition has there are 2 reduction reactions that require NADPH and an intermediate dehydration c. Process continued until Palmitate (C16) formed d. Unless longer FA needed to be made (in brain and other places) iv. Further Elongation (in brain) a. In ER b. Palmitate activated by adding CoA and then 2 Cs at a time c. Process is catalyzed by FA elongase What are the feed back inhibitors and activators of synthesis of fatty acids? a. Acetyl CoA- depending on levels = self regulation, controls

Kramers BIOCHEM Study Lipid Metabolism 8/26/10 total amount of citrate formed due to reciprical control of two enzymes a. Inhibits- PDH b. Stimulates- PC b. Insulina. Stimulates- PDH to upregulate synthesis of Acetyl CoA b. Upregulates- synthesis of citric lyase and malic enzyme What role does citrate, NADPH, and ATP play in Fatty Acid synthesis? i. Citrate- precursor to Acetyl CoA in cytoplasm also forms feedback as it can go to OAA pyruvate ii. NADPH- needed for reduction reactions in FAS iii.ATP needed to activate (phosporylate) synthesis reactions a. ACC- Added to ACC to deactivate enzyme - After FA are synthesized they get converted to Triacyl glycerols (TAGs) for storage to be used as fuel later How are TAGs synthesized? Location is in the liver or fat cells LIVER i. Glycerol in liver converted to G-3-P (by glycerol kinase) ii. 2- Acyl-CoA (fatty acids) hook onto G-3-P to form Phosphatidic acid (fatty acid with Phosphate) iii.Phosphate leaves and forms Diacylglycerol iv. Third fatty acid is added = (TAG) FAT CELLS i. Glycolysis makes DHAP ii. DHAP G-3-P (by enzyme Glycerol phosphate dehydrogenase) iii. Follow 2-4 above What happens after TAGs are synthesized? a. VLDL creation and storage- TAGs have apoproteins that create very low density lipoproteins (VLDL) which are released into blood and go to target organs to help with cell membranes and cholesterol in membranes b. Mobilization- depends on whether you are fasting or feasting a. Fasting- Hormone Sensitive= Lipoprotein Lipase (LPL)released and TAGs broken down to FA and glycerol to be used for energy b. Fed- LPL helps breakdown TAGs back to FA and Glycerol What are the Regulatory factors/horomones of TAGs and Fatty Acid synthesis? a. Adiponectin- horomone secreted from adipocytes binds to AdipoR1 and AdipoR2 a. Inhibits FA synthesis by i. Stimulating cyclic AMP-activated protein kinase 2

Kramers BIOCHEM Study Lipid Metabolism 8/26/10 (AMPK) and Peroxisome Preliferator activated recepter a (PPAR-a) 1. AMPK- leads to enhanced FA degredation and leads to enhanced glucose uptake by cells in muscle and liver 2. PPAR-a- just enhanced FA degradation b. Leptin- hormone at first thought to control weight released from adipocytes and go to brain a. Brain binds and generates neuropeptide and signals that full b. Prob- more engaged receptors become more sensitized i. Means build a tolerance to getting full