Lipid metabolism Flashcards
what tissues do de novo fatty acid synthesis?
adipose (triglyceride storage), liver (export as VLDL), mammary tissue
what molecule is produced from action of fatty acid synthase?
palmitic acid, though it itself is pretty useless, needs to have acetyl-CoA added to it by acetyl coa synthetase
what do you need to make one 16 carbon palmitate chain?
eight 2 carbon acetyl-CoAs
Why is biotin essential for ACC action?
Carboxylation of biotin linked to biotin carrier protein followed by the transfer of activated CO2 to aceetyl-CoA
Fatty acid synthase diffs between bacteria and vertebrates
In bacteria, seven activities of FAS are performed by seven separate proteins. In vertebrates, seven activities are combined into one large polypeptide
FAS seven subunits
ACP center, AT, KS, MT, KR, HD and ER subunits
Formation of palmitate with FAS 4 general steps
- Acyl transfer from CoA to thiol groups on two domains of FAS
- Condensation of malonyl and acetyl groups
- Sequential reduction using NADPH, result in saturated acyl group lengthened by 2 carbons
- Transfer of growing acyl chain from ACP to condensing enzyme
what steps of TCA occur in the cytosol
citrate to oxaloacetate, OAA to malate, malate to pyruvate with regeneration of NADPH and release of CO2
where do you get most of your NADPH?
pentose phosphate pathway, convert glucose 6-phosphate to ribulose 5-phosphate, these drive FA synthesis
Sites of short term regulation in FA synthesis
- Citrate transporter in IMM, feedback inhibitition by fatty acyl CoAs
- Acetyl CoA carboxylase - catalyzes rate limiting step
Four ways ACC can be regulated
- Citrate, allosteric activator
- Phosphorylation to inactivate
- Fatty acyl coAs feedback inhibition
- Acetyl CoA required for polymer assembly
how do we make FA longer than 16 carbons?
Enzymes on cytosolic face of ER can add 1+ 2-carbon units to palmitate or unsaturated fatty acids, using malonyl CoA as donor
how do we generate unsaturated fatty acids?
de novo synthesis through intro of cis-double bonds into FA CoA chains by desaturases on ER. Employ a version of ETC that yields water and unsaturated FA
how do we get polyunsaturated fatty acids with double bonds beyond position d9?
Cannot be synthesized in mammals, we need to get them from our diet (ex linoleate, omega 3 fatty acids)
two ways to make glycerol 3-phosphate
glycerol kinase from glycerol in liver, glycerol 2-phosphate dehydrogenase from glucose/dihydroxyacetone phosphate in adipocyte
