BBMB 405 1st Edition Lecture 9 Outline of Last Lecture XIII Handout 1 28 XIV Chapter 22 Fatty Acid Metabolism A Introduction B Fatty Acid Degradation C Triacylglycerols are highly concentrated energy store Outline of Current Lecture XIV Chapter 22 Fatty Acid Metabolism D The utilization of fatty acids as fuel requires three stages of processing E Unsaturated and odd chain fatty acids require additional steps for degradation XV Handout 1 30 XVI Handout 2 2 Current Lecture XIV Chapter 22 Fatty Acid Metabolism A The utilization of fatty acids as fuel requires three stages of processing 1 Stages a Mobilization how and when Move triacylglycerol from adipocytes b Activated and transported into mitochondria c Degraded to acetyl CoA 2 Lipolysis 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 3 Triacylglycerols are hydrolyzed by hormone stimulated lipases a b Two major proteins activated by protein kinase A by phosphorylation Perilipin and Hormone Sensitive lipase c ATGL adipose triglyceride lipase activated by phosphorylated perilipin decrease tri to di CA cofactor d HSL hormone sensitive lipase di to mono e MAG lipase monoacylglycerol lipase non limiting lipase f g When starving fate of glycerol is to be converted to glucose h We don t have the enzymes to recycle glycerol into triacylglycerols glycerol kinase i 4 Fatty acids are linked to coenzyme A before they are oxidized a Tissues that cannot burn fatty acid red blood cells because they don t have mitochondria and brain because it only wants glucose b Non esterified fatty acid NEFA comes out of adipocyte also called free fatty acid but bound to protein c d e Synthetase reaction pyrophosphatase catalyze reaction f g h Note that there are two steps to this reaction i All reactions so far take place in cytosol 5 Carnitine carries long chain activated fatty acids into mitochondrial matrix a Fatty acids to CO2 b Long chain fatty acid reacts with carnitine to make acyl carnitine c 6 Acetyl CoA NADH and FADH2 are generated in each round of fatty acid oxidation a b c Beta oxidation d Makes C16 to C14 to C12 till to C4 then make 2 C2 and eventually all to AcetylCoA 7 The complete oxidation of palmitate yields 106 molecules of ATP a Sequence Activate 2 ATP Produce 8 acetyl CoA 80 ATP 7 FADH2 7 NADH FADH2 7 x 1 5 10 5 ATP NADH 7 x 2 5 17 5 ATP 10 5 17 5 80 2 106 ATP Net production b c Roughly 2x that of carbohydrate B 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 a b Trans delta 2 Enoyl CoA subject to hydration H2O breaks double bond c d 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 XV Handout 1 30 Fat in Diet try to decrease lipid intake by creating fake lipids A Olean Olestra 1 Hexa pepta or octa ester of sucrose sucrose polyester 2 If burnt about 9 kcal g but really 0 kcal g because indigestible 3 Objective of development develop a fat to increase intake of fat by premature babies 4 Side effects abdominal cramping less absorbtion of vitamin A D E and K because they stay soluble with lipids B Xenical Alli Orlistat Tetrahydrolipstatin 1 Saturated derivative of lipstatin 2 Lipistatin is potent inhibitor of pancreatic lipase 3 Designed to treat obesity by preventing absorption of lipids from diet 4 Inhibits gastric and pancreatic lipases 5 Treatment effects steatorrhea oily loose stools C Disorders of lipid digestion 1 Obstruction of bile secretion gallstones 2 Exclusion of pancreatic juice steatorrhea XVI Handout 2 2 A Disease associated with deficiency of carnitine normal is 30 to 90 micromolar deficient is less than 30 mm B Causes 1 Low rates of cellular carnitine synthesis 2 Low CAT1 and CAT2 activities 3 Low translocase activity C Symptoms 1 Muscle cramping shortage of ATP for relaxation 2 Overall weakness 3 Even Death D Treatment Feed medium chain fatty acids enter mitochondria as free acids without using carnitine E Classification of fatty acids 1 C2 to C5 Short Chain 2 C6 to C12 Medium Chain coconut oil 3 C14 to C20 Long Chain 4 C22 and longer Very long chain F Don t memorize reaction scheme at bottom of first page of handout G Do we need carnitine in our diet 1 As we work out muscle function become more efficient 2 Will supplemental carnitine improve muscle ability No because didn t improve carnitine concentration in muscle 3 Do we need to eat it No you already eat and make enough
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