BBMB 405 1nd Edition Lecture 10 Outline of Last Lecture XIV Chapter 22 Fatty Acid Metabolism A The utilization of fatty acids as fuel requires three stages of processing B Unsaturated and odd chain fatty acids require additional steps for degradation XV Handout 1 30 XVI Handout 2 2 Outline of Current Lecture XIV Chapter 22 Fatty Acid Metabolism C Unsaturated and odd chain fatty acids require additional steps for degradation Current Lecture XIV Chapter 22 Fatty Acid Metabolsim C Unsaturated and odd chain fatty acids require additional steps for degradation 1 An isomerase and a reductase are required for the oxidation of unsaturated fatty acids These notes represent a detailed interpretation of the professor s lecture GradeBuddy is best used as a supplement to your own notes not as a substitute a b Trans delta 2 Enoyl CoA subject to hydration H2O breaks double bond c d Pathway of oxidation of C18 2 e Difference of ATP production Don t need to make the double bond and FADH2 so less ATP production 2 Odd chain fatty acids yield propionyl CoA in the final thiolysis step a Propionyl CoA is final product 3C CoA is there any value Yes b Convert to Succinyl CoA c First step propionyl CoA carboxylase second step racemized third step methylmalonyl CoA mutase dependent on Vitamin B12 d Enter TCA cycle at step of succinyl CoA and are either converted to oxaloacetate or glucose in the liver gluconeogenesis e Handout 2 2 Sources of propionate propionyl CoA i f Digestive tract Ruman about 2kg day in dairy cow bacteria make propionate so cow has to remake glucose that it ate Large intestine about 5 g day in adult human Cecum between small and large intestine about 500 g day in horse ii Cell Metabolism methionine isoleucine threonine valine thymine uracil cholesterol tail propionyl CoA L Methylmalonyl CoA B12 Succinyl CoA iii Odd chain fatty acids iv Propionate is of some significance Handout 2 2 Methylmalonic aciduria i Methylmalonic gets in urine and has a negative charge has to be countered so release Na to nutralize ii Autosomal Recessive disorder iii Cause iv v Mutation in L methylmalonyl CoA mutase B12 requiring enzyme Deficiency of Vitamin B12 in diet Thus propionyl CoA Succinyl CoA is slow L Methylmalonyl CoA isn t converted to succinyl CoA but is converted to methylmalonic acid and dumped into urine Symptoms Failure to thrive dehydration Skin lesions Developmental delay Lower glomerular filtration rate Treatment if not treated result in death Limit protein intake no excess protein so minimize amino acids to propinyl Increase carnitine Hemodialysis if necessary to remove NH3 and metabolic acidosis liver starts function less and there is more ammonia in blood 3 Vitamin B12 contains a corrin ring and a cobalt atom a Cobalt atom has different molecules attached b Handout 2 2 Vitamin B12 i Required nutrient 1 2 micrograms day ii Only in animal derived foods beef liver oyster not in plants iii Synthesized by bacteria in intestinal tract need Co iv Carrier mediated absorption with aid of R protein and intrinsic factor v Forms 5 deoxyadenosylcobalamin Methylcobalamin Hydroxycobalamin CN poisoning Active coenzyme forms Cyanocabalamin form in vitamin pills vi Pernicious anemia vii If deficiency often injected because of poor absorption viii Methionine synthesis from homocysteine homocysteine MeTHFA methionine THFA ix dNDP synthesis in bacteria NDP NADPH dNDP NADP 4 Mechanism Methylmalonyl CoA mutase catalyzes a rearrangement to form succinyl CoA skipped 5 Fatty acids are also oxidized in peroxisomes normally in mitochondria a Handout 2 4 Peroxisomal Oxidation of fatty acids i Metabolic function Chain shortening of very long chain fatty acids prostaglandins dicarboxylic acids and various xenobiotic compounds Unsaturated fatty acids used also Major end product is C8 CoA octanoyl CoA ii Less ATP fatty acid because FADH2 e O2 via catalase rather than oxidation phosphorylation iii Questions Reoxidation of NADH Exit of acyl CoA usually octanoyl CoA Physiological significance degradation of very long chain fatty acid b Handout 2 4 Peroxisomal diseases i ii X linked adrenoleukodystrophy X ALD Defective intake of fatty acids by peroxisomes transporter missing Very long chain fatty acids VLCFA ex C24 0 accumulate in tissues and cause symptoms Zellweger syndrome No peroxisomal enzymes Accumulation of VLCFA Death by 6 months of age No cure c Handout 2 4 Omega and alpha oxidation of fatty acids i ii Omega oxidation of fatty acids Happens in endoplasmic recticulum of liver Could lead to 4 carbons that are glucogenic Use amount of adipate in urine to measure reaction efficiency if working properly Alpha oxidation of fatty acids Happens in peroxisomes Used on branched chain fatty acids If reaction doesn t happen acid accumulates and causes nerve damage that is why reaction so important 6 Ketone bodies are formed from acetyl CoA when fat breakdown predominates introduction a What if too much FA coming into liver excess end up as ketone bodies KB and dumped into blood stream b Fatty acid irreversible Pyruvate glucose c Ac CoA d KB TCA cycle 2CO2 e Fatty acid oxidation is incomplete ketone metabolism f Anything that produce Ac CoA is non glucogenic g Handout 2 4 Major Fates of FA in liver h FA FA CoA TAG in VLDL very low density and get out of liver i FA CoA via beta oxidation Ac CoA KB when lover overwhelmed or 2CO2 via TCA cycle j Ketone bodies acetoacetate Beta Hydroxybutyrate not really ketone ketone possibly acetate k Enzymes of ketogenesis Thiolase HMG CoA synthase HMG CoA lyase BHBA dehydrogenase l Will continue next lecture