Fatty Acid Synthesis Flashcards
how many carbons does palmitate have?
16 carbons
which part of the cell does fatty acid synthesis occur?
cytosol/cytoplasm
which organs does biosynthesis of FA happen?
liver, mammary gland, adipose tissue (mainly)
kidney, brain, lungs
where do we find acetylcoA?
mitochondria
acetylcoA will move into the cytoplasm - where FA synthesis occurs - as CITRATE!
what enzyme converts acetyl coA to citrate?
citrate synthase
phosphorylation of acetyl coA carboxylase
deactivation of the enzyme
dephosphorylation of acetyl coA carboxylase
activates the enzyme
excess carbs, proteins, and other molec obtained from body can be turned to ____ and stored as _____/
fatty acids, triacylglycerols
co-factor requirements of FA synthesis
NADPH, ATP, manganese, biotin, HCO3
what is the immediate substrate of FA synthesis?
acetyl coA
what is the end product of FA synthesis ?
free palmitol
what is the initial and controlling step of FA synthesis?
production of malonyl coA
what provides all the carbon atoms in FA synthesis?
acetyl coA
acetyl coA is made from _____ in mitochondria
pyruvate
what enzyme converts pyruvate to acetyl coA in mitochondria?
pyruvate dehydrogenase
How does acetyl coA become available for FA synthesis?
acetyl coA moves out from mitochondria and into cytoplasm as CITRATE while being co-transported w/ malate.
Citrate is then further cleaved by ATP CITRATE LYASE w/ utilization of energy & addition of coA – forming ACETYL COA.
what condition activates ATP citrate lyase?
well-fed state (more substrates available for FA synthesis)
what is the effect of the inhibition of ATP citrate lyase?
decreased formation of citrate to acetyl coA for FA synthesis
how is malonyl coA formed?
acetyl coA undergoes carboxylation by acetyl coA carboxylase into malonyl coA.
CO2 and ATP are used in this process.
what step in FA synthesis do biotin and HCO3 get to work?
process of converting acetyl coA to malony coA
which is also the controlled step in the entire process
what are the 3 sources of NADPH in FA synthesis?
- PPP (major)
- activity of malic enzyme (major)
- activity of isocitrate dehydrogenase (minor)
what enzyme assembles fatty acid chain in FA synthesis?
fatty acid synthase
what counter-regulatory hormones deactivate acetyl coA carboxylase?
glucagon
epinephrine
catecholamines
how is acetyl coA carboxylase regulated short-term?
through hormones
counter-regulatory hormones phosphorylate acetyl coA carboxylase leading to its deactivation.
INSULIN, on the contrary, dephosphorylates acetyl coA carboxylase leading to its activation.
what is the effect of long chain fatty acyl coA and citrate on acetyl coA carboxylase?
long chain fatty acyl coA deactivates enzyme.
citrate activates enzyme.
does insulin promote FA synthesis
yes b/c insulin normally is an ANABOLIC hormone
long term regulation of Acetyl coA carboxylase
high-calorie/high carbohydrate diets
increased enzyme synthesis
a multienzyme complex of one polypeptide chain w/ 7 separate enzyme activities & an acyl carrier protein
fatty acid synthase
ACP contains _______ carrying intermediates of FA synthesis
phosphopantotheine moiety
what part of ACP do acetyl coA and malonyl groups esterify?
– SH group
what is the first step fo FA elongation process?
a. acetyl coA combine w/ – SH group (nz. Acetyl transcyclase)
b. malonyl combines w/ –SH group on phosphopantotheine of ACP (nz. Malonyl transcyclase)
forming 5-carbon ACYL-MALONYL enzyme.
2nd step of FA elongation
decarboxylation of acyl-malonyl enzyme into 3-ketoacyl enzyme/ acetoacetyl enzyme (nz. 3-ketoacyl synthase_
3rd step of FA elongation
reduction of acetoacetyl enzyme –> D(-)-3-hydroxyacyl enzyme (nz. 3-ketoacyl reductase)
4th step of FA elongation
dehydration of D(-)-3-hydroxyacyl enzyme –> 2,3 unsaturated acyl enzyme (nz. hydratase)
5th step of FA elongation
reduction of 2,3 unsaturated acyl enzyme –> acyl enzyme (nz. enoyl reductase)
after the FA is synthesized, what enzyme is responsible for its release?
thioesterase
fates of free palmitate
- esterification to acylglycerol
- chain elongation /desaturation
- esterification to cholesteryl esters (cholesterol)
Stoichiometry of FA synthesis
Acetyl coA + 7 malonyl coA + 14 NADPH + 14 H+
—->
Palmitic + 7CO2 + 6H2O + 8 Coenz A + 14 NADP
effect of insulin on intracellular cAMP
decreases intracellular cAMP level —> LYPOLYSIS INHIBITED in adipose tissue –> decreased concentration of plasma FFA and long chain acyl coA
what is effect of insulin in adipose tissue?
converts inactive form of pyruvate dehydrogenase to active form