21: lipid synthesis Flashcards
Do you know how to name fatty acids? and recognize structure?
count from the carboxyl carbon, unsaturations denoted with ∆. for common naming, saturated ate -ate and unsaturated are -oleic acid, eg palmitate and palmitoleic acid remember most fatty acids are even numbers.
Eicosanoids structure and function
20C polyunsaturated FA with derivatization
signaling, such as PGEs and thromboxanes
triacylglycerols structure and function
glycerol molecule with three fatty acids
energy storage
glycerophospholipids structure and function
glycerol molecule with two FA and a phosphate linked head group, can have a few different head group that define identity
membrane components
cholesterol structure and function
27C, multi cyclic, derived from isoprene units (from mevalonate)
membrane component and precursor for steroid hormones
Describe the steps of biosynthesis of FAs
occurs in cytoplasm
- synthesize malonyl-CoA by AcetylCoA carboxylase ACC
- long C chains of FA assembled in 4 step sequence by FA synthase
- acetate precursor shuttled into cytoplasm as citrate
- desaturation requires mixed-function oxidase activity
mechanism of ACC acetyl-coA carboxylase
21 Pt 1 slide 5
uses biotin carboxylase and ATP to carry CO2 (from HCO3-). then transcarboxylase combines acetyl-coA and CO2 to make malonyl-coA
1st, committed step in FA synthesis (highly regulated)
mechanism of FAS fatty acid synthase
21 pt1 slide 6
multi enzyme complex has long and short arm. Malonyl and acetyl precursors are activated by a thioester. decarboxylation condensation occurs and the acetyl group is added to the malonyl. reduction occurs using NADPH and then dehydration and then another reduction from NADPH. Then another malonyl is added and the cycle repeats.
Condensation, Reduction, Dehydration, Reduction
FAS involves getting rid of CO2, is this wasteful since we just worked so hard to incorporate CO2??
Nah. condensation of an acetyl group to and acyl chain is an endergonic process, so the CO2 is needed as a good leaving group to make the process favorable. CO2 loss during condensation results in an exergonic process
what is acyl carrier protein and how does it work?
ACP has a 4’ phosphopantethiene group which acts as a flexible arm. it has a thiol group which esterifies to malonyl groups and can transfer the growing product to the next enzyme active site.
how many carbons is palmitate?
16
what is required to make one molecule of palmitate? stoichiometry practice
ACC (7 cycles): needs 7 acetyl-coA + 7 CO2 + 7 ATP to produce 7 malonyl CoA
FAS (7 cycles): needs 1 acetyl-coA + 7 malonyl-coA + 14 NADPH + 14 H+ to produce one palmitate
NET: 8 acetyl-coA + 7 ATP + 14 NADPH + 14 H+ –> palmitate + 8 CoA + 7ADP + 7 Pi + 14 NADp + 6H2O
what are some homologues to FAS in other organisms
bacteria, plants: seven activities in seven separate polypeptides
yeast: seven activities in two separate peptides
vertebrates: seven activities in one large polypeptide
where in the cell does FA synthesis take place? plant and animal
animal cell: FA synthesis in cytosol, elongation and desaturation and modifications in ER and mitochondria (elongation)
plant cell: FA synthesis in chloroplast, elongation and desaturation and modifications in ER and mitochondria (elongation)
where does the acetyl-coA for FA synthesis come from?
nearly all from mitochondrial oxidation of pyruvate and amino acid catabolism. mitochondrial membrane is impermeable to acetyl-coA, so it must be made into citrate and go through citrate transporter to get out
how is FA synthesis regulated?
ACC is rate limiting step. palmitate (the ultimate product) inhibits ACC and citrate is and allosteric activator. ACC can also by phosphorylated. glucagon and epinephrine inhibit ACC. It is important to keep tight control bc it is so energetically costly
what happens if a FA longer than 16 C is needed?
fatty elongation system is in the smooth ER and mitochondria.