SYLLABUS 9: Fatty acid biosynthesis Flashcards Preview

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Flashcards in SYLLABUS 9: Fatty acid biosynthesis Deck (22):

when are fatty acids synthesized

when carbohydrate (glucose) and protein (amino acid) levels are high


where does fatty acid biosynthesis occur

cytoplasm of most cells, w/ liver the most reactive


what happens to excess fatty acids in liver

exported as triglycerides packaged in very low density lipoproteins (VLDL) to adipose tissue, where they're stored 


what metabolites does FA synthesis require



what elevates/decreases FA synthesis?

insulin: elevates FA synthesis

glucagon: decreases FA synthesis


in high glucose conditions, what are the steps that set up fatty acid synthesis in the cytosol?

high glugose => excess FA synthesis 

glucose is metabolized by glycolysis, PDH to acetyl CoA 

acetyl CoA enters TCA cycle, produces citrate

some of the citrate continues through TCA cycle to produce ATP for FA synthesis; some citrate leaves the mito on TCA carrier to the cyto, where it produces acetyl CoA 

cytosolic acetyl CoA enters lipogenesis to produce palmitic acid 



what happens to palmitate produced by fatty acid synthase?

1) used or store din the liver 


2) transported as VLDL to adipose tissue, where it's stored 


3) converted to longer chain fatty acids (like stearate, C18) by elongation enzymes or monounsaturated fatty acids (eg oleic acid) by desaturation enzymes 



what happens to acetyol coA in the mito produced from glucose?

cannot leave the mito to become available in cyto for fatty acid biosynthesis 

therefore must react w/ OAA to produce citrate which is transported out of mito via citrate shuttle


when does the citrate shuttle function/how

mito acetyl CoA cannot leave the mito, so:

mitochodnrial acetyl CoA reacts w/ OAA to produce citrate 

citrate transported out of the mito via via the citrate shuttle, on the TCA carrier 

citrate is leaved by citrate lyase, an ATP-dependent enzyme, to OAA + acetyl CoA 

OAA is reduced to malate 

malate 1) reenters the mito, oxidized by to OAA or 2) is oxidized in cyto by malic enzyme to produce NADPH for FA synthesis


how is OAA regenerated in the mito

from either Pyruvate via pyruvate carboxylase 

or from malate 


in the high energy state, what happens to glycolysis vs fatty acid synthesis? what enzymes does this impact? 

glycolysis slows & fatty acid synthesis is stimulated in the high energy state 

isocitrate DH slows 



what is the rate limiting step of FA synthesis

acetyl coA carboxylase


describe the rate limiting step of FA synthesis

FA synthesis requires acetyl CoA and malonyl CoA 

malonyl CoA is synthesized from acetyl CoA by acetyl CoA carboxylase, which is the rate limiting enzyme of FA synthesis 

biotin is the cofactor for the carboxylation 



what activates vs inhibits acetyl CoA carboxylase? 

activators: citrate, insulin - which dephosphorylates it

inhibitors: palmitoyl CoA (product), AMP activated kinase, glucagon/cAMP-PKA


is acetyl coA carboxylase activated or inactivated when phosphorylated

inactive when phosphorylated - which is how AMP activated kinase, glucagon/cAMP-PKA inactivate it


what are sources of NADPH for fatty acid synthesis?

1) first step of the PPP pathway 

2) malic enzyme under lipogenic conditions 

3) transhydrogenase


describe how palmitate is formed? 

acetyl CoA and malonyl CoA from the ACC reaction are transferred to the fatty acyl synthase (FAS) complex 

acetyl CoA binds to a cysteine group of the condensing enzyme in teh FAS complex 

malonyl CoA binds to the acyl carrier protein (ACP) of the FAS 

ATP drives reaction of condensing enzyme making a 4C product from acetyl CoA and Malonyl CoA 

This 4C intermediate + CO2 now are produced 

the 4C acetyoacetyl CoA is then reduced, hydrated, and reduced again to produce a saturated 4C butyryl CoA 

these steps require NADPH 

butyryl CoA now repeats teh cycle: attachess cyteine SH of dondensing enzyme, condenses with malony CoA, reduces, hydration, reduction to produce a 6C fatty acid 

ULTIMATELY: C16 palmitate is formed, which can't bind to the cysteine and is released from the FAS complex 


how is palmitate aka palmitoyl coA used?

1) stored as triglycerides, esp in liver and adipose tissue 

2) forms phospholipids needed for membranes 

3) can be elongated to produce C18, C20 fatty acids 

4) can be desaturated to produce unsaturated fatty acids


how does acetyl coa carboxylase regulate fatty acid synthesis

it is the rate limiting enzyme for formation of malonyl coa from acetyl coa 


how do lipogenic conditions regulate fatty acid synthesis?

high glucose, genes for citrate cleavage enzyme, malic enzyme acetyl coA carobxylase, and FAS are activated by SREBP which itself is activated by insulin and inactivated by glucagon


how does malonyl CoA regulate fatty acid synthesis

malonyl CoA is needed for FA synthesis 

it's a powerful inhibitor of acyl carnitine transferases which bring FA into mito for B-oxidation 

so FA synthesis and oxidation don't occur at same time


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