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U-M BIOLCHEM 415 - Fatty Acid Oxidation
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BIOLCHEM 415 1st Edition Lecture 23Outline of Last Lecture I. Photosynthesis occurs in the chloroplast and generates NADPH and ATPII. Electron flow creates the energy in photosynthesisIII. The Calvin Cycle produces carbohydrates from CO2IV. The Pentose Phosphate pathway generates NADPH and riboseOutline of Current Lecture V. Fatty acids stored as triacylglycerides are a major source of energyVI. Fatty acid oxidation generates much more energy then glycolysisVII. Complete oxidation requires TCA cycle for greatest efficiencyVIII. Ketone bodies formed from acetyl CoA can be a great energy source and a deadlymetaboliteCurrent Lecture4 major physiological roles of fatty acids 1 – building blocks of phospholipids and glycolipids (already discussed)2 – anchors for membrane-associated proteins (already discussed)3 – Fuel Molecules (This Lecture)- triacylglycerols- uncharged esters- stored in adipose tissue4 – hormones and second messengers (to be discussed later)Stored triacylglycerides- processed in 3 stages- more available than glucose1 – mobilized from adipose 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.- degraded to fatty acids/glycerol- transported to energy-requiring tissues2 – processing in target tissues/cells- fatty acids activated - transported to the mitochondria3 – energy generationMobilization- triacylglycerides stored in adipocytes as lipid droplet- degraded by triacylglycerol lipase (highly regulated enzyme)- 3 fatty acids per glycerol- stimulated by energy need (epinephrine)- 7TM receptors- adenolcyclase as messenger- PKA phosphorylation- perilipin and the lipase (fully activates)- transport to tissue through blood stream- not very blood soluble- serum albumin is the major carrier- glycerol gluconeogenesis/glycolysis- fatty acids energy source via oxidation in the mitochondria- acetyl CoA is a major productActivation for Transport into mitochondria- requires ATP - Acyl adenylate adds CoA- acyl CoA can enter mitochondria- acyl CoA can’t cross the membrane- loaded onto carnitine- releases CoA and becomes acylcarnitine- this crosses the membrane- process is reversed in the mitochondria- energy production is compromised if it can’t enter the mitochondriaEnergy generation- fatty acid oxidation at β-C (β-oxidation)- 2 Cs split off as acetyl CoA- generate NADH and FADH21 – acyl CoA dehydrogenase- oxidation- FADH2 generated - trans double bond formed2 – hydration by enol CoA hydratase- breaks double bond with –OH3 – oxidation of –OH by hydroxyacyl CoA dehydrogenase- yieldsketo group and NADH4 – Thiolysis by β-ketothiolase- cleavage by thiol group- acetyl CoA and acyl(n-2) CoA- reactions keep going until acyl CoA exhausted- looks like part of TCA cycle- one fatty acid chain can yield up to 106 ATP- 3 chains/moleculeOxidation of unsaturated fatty acids- additional enzymes required - β-oxidation normal until double bond reached- isomerase shifts position of double bond- at odd positions - isomerase and reductase required at even positionsOdd numbered fatty acids - products = C-2 acetyl CoA and C-3 propionyl CoA- propionyl converted to succinyl CoA and enter TCA cycleVitamin B12- mainly obtained from bacteria- meat and other animal products- intrinsic factor- glycoprotein required for absorbtion- lack of this protein results in B12 deficiencyMetabolic Interdependence- complete oxidation requires TCA cycle to be most efficient- acetyl CoA adds NO C net gain to TCA cycle- means glucose can’t be generated from fatty acidsKetone bodies- formed from acetyl CoA- when fatty acid oxidation exceeds TCA cycle capacity- 3 acetyl CoA’s form HMG-CoA- 2 acetyl CoA’s produce Acetoacetate- acetoacetate acetone OR 3-Hydroxybutyrate (reduction)- conditions that lead to ketone body formation- fasting- high fat/low carb diets- diabetes- energy source- especially during starvation- deadly metabolite- acidosis, ketosis, coma, eventual death- causes blood pH to


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U-M BIOLCHEM 415 - Fatty Acid Oxidation

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