MCB 2000 Midterm: Peer Review 11 Review

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University of Connecticut
Molecular and Cell Biology
MCB 2000

Wednesday, April 19, 2017 MCB 2000 Peer Review 11 - four main functions of fatty acids • phospholipids in membranes • triglycerides for energy storage (less weight than glycogen) • secondary messengers • covalent modification of proteins - store water with glycogens, hydrophobic with fatty acids Synthesis of Lipids - only in fed state - high I/G ratio - lipid synthesis = gain weight - excess caloric intake - major source is from carbohydrates (needs carbon chains) - Acetyl-CoA -> fatty acids (insulin present) - no insulin present: acetyl coa -> ketone bodies (buildup of heat, severely fasted state) - synthesized from dietary proteins - main tissues: liver and adipose tissues - low carb diet: lack of carb/glucose -> drop in insulin levels -> biosynthetic pathways decrease activity -> less available energy, body must find other sources (ketone bodies/breaking down fatty acid storage) -> extended low carb: body will not be able to function per üsh Fatty Acid Synthesis - acetyl coa is starting substrate - reducing equivalents • NADPH -> reduced amount of glycolysis with NADH and less starting material, both processes can occur simultaneously with NADPH 1 Wednesday, April 19, 2017 • pentose phosphate pathway • malic enzyme - integration of glycolysis, TCA cycle, and pentose phosphate pathway Reactions - 2 carbon (acetyl coa) units added together - activation by conversion from acetyl coa -> malonyl coa - decarboxylation of malonyl coa + NADPH reduction drives growth - 8 acetyl-CoA + 7 ATP + 8 ATP Acetyl CoA - glucose converted to pyruvate -> Acetyl CoA through PDC - but transport out of mito by citrate, get citrate by binding OAA and acetyl CoA - OAA is limiting (reverse reaction is favored, and with citrate synthase, drives TCA cycle) - production allosterically regulated by Acetyl-CoA - pyruvate carboxylase - once Acetyl-CoA builds up, it negatively regulates PDC and positively regulates PC - OAA + acetyl coa -> citrate that moves out of mito and separates into OAA + acetyl-coa where is can be used for FAS - insulin activates PDC via dephosphorylation - PDC has much lower Km than pyruvate -> negative feedback loop Citrate Lyase - Citrate lyase + ATP to cleave citrate -> acetyl-coa and OAA (cleavage not through hydrolysis) - Malate dehydrogenase + NADH reduces OAA -> malate - malic enzyme converts malate -> pyruvate and NADPH NADPH - comes from 2 sources: pentose phosphate pathway, malic enzyme - only in biosynthetic pathways 2 Wednesday, April 19, 2017 - NADH -> primary role is to shuttle e- to ETC for oxidative phosphorylation Acetyl-CoA Carboxylase (ACC) - activation step, happens 7 times - irreversible rate limiting committed step - requires biotin as a coenzyme - Acetyl-CoA +ATP + HCO3 -> Malonyl-CoA - bicarbonate is carbon source being added on - malonyl-coa can be thought of as an activated carbon 2 donor (brings in all the carbons to create fatty acid chain) Regulation of ACC - AMP-dependent protein kinase -> activated by AMP, inhibited by ATP - protein phosphatase 2A, stimulated by insulin (cleaves off phosphate) - positive: - citrate binds and causes inactive (phosphorylated) form to gain activity by causing polymerization of inactive dimers - more efficient - negative: - palmitoyl coa (last step before fatty acid is cleaved off) causes depolymerization of dimers = feedback inhibition Lipogenesis - this is the big boy - fatty acid synthase - dimer of 2 chains -> each has 7 catalytic activities, huge - carries out: condensation, reduction, dehydration Priming and Condensation Reaction - attachment of acetyl and malonyl groups to acyl carrier protein (ACP) - ACP contains a phosphapantetheine group to form thioester bond - catalyzed by malonylacetyl transferase (MAT) 3 Wednesday, April 19, 2017 - priming comes first: acetyl and malonyl attached first - condensing enzyme (KS) - acetyl-coa is transferred to the sulfhydryl group on this enzyme (MAT) - allows for malonyl-coa to attach to ACP - both acetyl and malonyl attached via thioester bonds and in close proximity to each other - K
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