Exam 3 Lipid Metabolism I part a Flashcards
what is the major source of carbon for FA synthesis?
dietary carbohydrates (carbs we eat is converted into FAs)
FA synthesis occurs primarily in _ but also _
primarily in liver but also in adipose tissue
FA synthesis requires coordination between _ and _ reactions
cytosolic and mitochondrial reactions
what is the precursor of FA synthesis?
Acetyl CoA (2 carbon molecule)
what is phase I in FA synthesis
cytosolic entry of Acetyl CoA (made in the mito matrix but needed in cytoplasm)
what is phase II in FA synthesis
generation of malonyl CoA (a 3 carbon molecule, from 2 carbon acetyl CoA, that is a substrate catalyzed by FA synthase)
what is phase III in FA synthesis
FA chain formation (7 reactions catalyzed by FA synthase)
how do we get acetyl coA into the cytosol?
- citrate synthase catalyzes acetyl coA with OAA into citrate (in mito matrix) and citrate is trasported out
what happens when citrate is trasported to the cytosol?
citrate lyase converts citrate back into acetyl coA and OAA.
what happens to the products of citrate lyase?
acetyl coA is used for FA synthesis and OAA is reduced to malate by malate dehydrogenase
how do we regenerate OAA?
- cytosolic malate is converted into pyruvate which is transported into the mito
- malate transported to mito and oxidized into OAA by malate dehydrogenase
what is the RLS of FA synthesis
acetyl coA (2-C) converted into malonyl coA (3-C)
what is the rate limiting enzyme of FA synthesis
acetyl coA carboxylase (ACC)
where do we get the 3rd carbon from to make malonyl coA?
CO2
ACC uses ATP and _ as cofactor
biotin
malonyl coA is a substrate for FA Synthase (FAS) and acts like its regulator how?
inhibits carnitine acyltransferase (RLS in FA degradation)
we want to go foward with malonyl coA so inhibits degradation of FA since we want synthesis
how do we accomplish phase III, FA chain formation?
2-C units from malonyl coA are sequentially added to growing fatty acyl chain in 7 rxns to form palmitate (16:0)
FAS complex is present where?
in cytoplassm
FAS is a large _ complex
multi-enzyme
FAS is composed of _ arranged in _ to _ conformation
2 identical dimers arranged in head to tail conformation
Each monomer, of the dimer of FAS, has _ enzyme activities and an _ protein
7 enzymatic activities and an acyl carrier protein (ACP)
what is the purpose of ACP having a flexible arm?
Function is to pick a substrate and take it to one of the 7 enzymes and then takes product (substrate) forfmed to the next enzyme in chain
Stoichiometry:
1 acetyl coA + 7 malonyle coA + 14 NADPH + 14 H+ =
palmitate + 14 NADP+ + 8 CoA + 6 H2O
why does FA synthesis use NADPH?
accessory component that helps in reduction
what are the sources of NADPH?
malic enzyme yields 1 molecule of NADPH and PPP yields 2-12 molecules of NADPH
what is the cycle of FAS?
condensation, reduction, dehydration, reduction (repeated 6x more)
what are the 3 enzymes of FA synthesis regulation?
- ATP citrate lyase (phase I)
- acetyl coA carboxylase (phase II and RLS)
- FA synthase (phase III)
how is ATP citrate lyase stimulated/induced?
- stimulated by phosphorylation
2. gene expression induced by glucose/insulin (high glucose/high insulin want to convert into storage FA form)
how is ATP citrate lyase counteracted/negated?
- induction of gene expression counteracted by polyunsaturated FAs (PUFAs)
- induction of gene expression counteracted by leptin (H that senses fat content in body)
ACC is inactive _, active _
inactive dimer, active polymer
ACC allosteric reguolation?
- citrate activates
2. long chain FAs (palmitate) inactivate
ACC phosphorylation?
phosphorylation = inactivated
- epinephrine activates PKA
- glucagon activates PKA
- AMP activates AMP kinase (energy sensor)
ACC dephosphorylation?
dephosphorylation = activation
1. insulin activates protein phosphatase
ACC induction?
gene expression up-regulated by high carb/low fat diet
what increases allosteric effect activity in regulation of FAS?
presence of phosphorylated sugars ie G6P/G1P
what induces gene levels in regulation of FAS?
- insulin and glucocorticoid hormones INCREASES synthesis
2. high carb/low fat diet INCREASES synthesis
what represses gene levels in regulation of FAS?
- high fat diet and STARVATION lowers synthesis
2. high PUFA suppresses synthesis
