2 lipid oxidation (1).ppt
- 1. Dr. Maryam Mastoor Asst. Professor Biochemistry Amna Inayat Medical College
- 2. Catabolism of FA (Oxidation) Beta oxidation in Mitochondria, V long chain FA oxidation in peroxisomes Anabolism of FA (De-novo synthesis) Ketone body metabolism Cholesterol metabolism Lipoprotein metabolism
- 3. Triacylglycerol Fatty acids Acetyl CoA TCA CO2 Overview of lipid metabolism
- 4. » Fatty acids are stored as Triacylglycerol » Constitute 84% of stored energy + Protein - 15% + Carbohydrate (glucose or glycogen) - <1% » Fatty acids mobilized from Triacylglycerol are oxidized to meet the energy needs of a cell
- 6. Stage 1: Mobilization of FA from TG inside tissues Stage 2: Activation of FA in cytosol Stage 4: Degradation of FA by beta oxidation into acetyl-CoA inside mitochondrial matrix Stage 3: Transportation of activated FA from cytosol/outer to inner mitochondrial membrane FA Catabolism (FA oxidation)
- 7. » RBCS have no mitochondria, so no way to oxidize fatty acids. The brain has mitochondria but is made largely out of lipids; metabolizing lipids for energy would be dangerous to the structure of brain cells
- 8. Stage 1: Mobilization of FA from TG inside adipose tissues
- 9. Mobilization of FA made from TG inside tissues
- 10. (Adrenalin, Glucagon, ACTH) Mobilization of FA from TG inside tissues
- 11. Mobilization of FA from TG inside tissues
- 13. Stage 1: Mobilization of FA from TG inside tissues Stage 2: Activation of FA in cytosol Stage 4: Degradation of FA by beta oxidation into acetyl-CoA inside mitochondrial matrix Stage 3: Transportation of activated FA from cytosol/outer to inner mitochondrial membrane FA Catabolism (FA oxidation)
- 14. - β-oxidation - Peroxisomal FA oxidation - α-oxidation - ω-oxidation - Modified β-oxidation pathway
- 17. β Oxidation of fatty acid is oxidation of fatty acid at the β carbon atom with successive removal of two carbon atoms as acetyl CoA Long assay
- 20. 3 Steps of Fatty acid Beta Oxidation: (1) Activation of fatty acids takes place on the outer mitochondrial membrane in cytosol (2) Transport of activated FA into the mitochondria (3) Degradation to two-carbon fragments (as acetyl CoA) in the mitochondrial matrix (b-oxidation pathway)
- 21. 1 • Activation of fatty acids in the cytosol (near outer mitochondrial membrane) 2 • Transport of activated fatty acids into mitochondria 3 • β-Oxidation proper in the mitochondria; Degradation to two- carbon fragments (as acetyl CoA) in the mitochondrial matrix
- 22. Occurs in cytosol at outer mitochondrial membrane for long chain fatty acids Fatty Acid Acyl-CoA Fatty acids are converted to Fatty Acyl CoA (thioesters) by enzyme acyl-CoA synthetase by use of ATP (i.e ATP dependent) The resultant PPi released is hydrolyzed by a pyrophosphatase to 2 Pi Two phosphoanhydride bonds (two ATP equivalents) are consumed to activate one fatty acid to a thioester
- 23. Acids Pyrophosphate (with 2 phosphoanhydride bonds) STEP1 STEP2 Fatty acyl CoA Acyl CoA synthetase
- 25. »Step 2 beta oxidation
- 27. CAT-I CAT-II
- 33. Overall process of β-oxidation of Palmitoyl CoA (C16) 7 Cycles of β –oxidation with Successive removal of 2 carbon units Palmitoyl-CoA
- 34. Oxidation by FAD Hydration Oxidation by NAD Thiolysis
- 36. ENERGETICS OF COMPLETE OXIDATION OF PALMITIC ACID Oxidation 7 cycles 7 FADH2 x 2ATP/FADH2 14 (10.5) 7 NADH + H+ x 3ATP/NADH 21 (17.5) From 8 acetyl CoA Each acetyl CoA provides 12 ATP by TCA cycle 96 (80) Total ATP produced from one palmitic acid 131 (108) Total ATP used for activation 2 NET YIELD OF ATP 129 (106)
- 38. AVAILABILITY OF FATTY ACIDS Hormones Glucagon Epinephrine Insulin SYNTHESIS OF FATTY ACIDS Inhibition of carnitine acyl transferase I by malonyl CoA
- 39. Provision of energy • 20-30% of energy requirement of the cell • Major pathway Ketone bodies • Diabetes • Starvation Synthesis of biomolecules from acetyl CoA • Acetylcholine • Cholesterol
- 40. Oxidized by β–oxidation in the same way as that of even number, except the are the end products
- 42. β-OXIDATION OF ODD CHAIN FATTY ACIDS D L
- 43. • Requires additional enzymes • Isomerase and reductase Presence of double bonds
- 46. • Minor pathway • Involves oxdn of fatty acids at α carbon atom • One carbon is removed from the carboxyl end and released as CO2 • Occurs in endoplasmic reticulum • Phytanic acid oxidation α-OXIDATION
- 47. It is a minor pathway Takes place in microsomes Involves oxidation of last carbon atom ( ω carbon) More common with medium chain fatty acids
- 50. Can occur particularly in the newborn— and especially in preterm infants Carnitine deficiency Features • Muscle cramps, muscle weakness
- 51. • Caused by eating the unripe fruit of the akee tree, which contains a toxin, hypoglycin, that inactivates medium and short chain acyl-CoA dehydrogenase, inhibiting β-oxidation and causing hypoglycemia. Jamaican vomiting sickness
- 52. Is a rare neurologic disorder due to a defect that causes the accumulation of phytanic acid, which is found in plant foodstuffs and blocks β-oxidation. Refsum’s disease Features • Cerebral ataxia • Periphaeral neuropathy • Retinitis pigmentosa
- 53. Occurs in individuals with a rare inherited absence of peroxisomes in all tissues. Zellweger’s syndrome