10/19 Lipogenesis Flashcards
rate limiting step/enzyme of FA synthesis
acetyl-CoA carboxylase (ACC)
acetyl-CoA —-> malonyl-CoA
(+) insulin, citrate
(-) Palmitoyl-CoA, AMP
big picture, what does insulin stimulate
cytosolic glucose —> cytosolic acetyl-CoA
Regulation of ACC
(+) insulin, citrate
(-) Palmitoyl-CoA, AMP
Pi= inactivation De-Pi= activation
induced by a high calorie diet
decreased by a low calorie diet
what inhibits lipolysis while lipogenesis is going
insulin inhibits hormone sensitive lipases (TG–>FA)
malonyl-CoA inhibits CPT1 (FA–>Acetyl Coa and NADH)
general consequence of TG accummulation
obseity, increased risk for metabolic syndrome
increased BP/TGs/LDL-C, glucose intolerance, insulin resistance
consequence of liver TG accummulation (non-alcoholic)
NAFLD
liver statosis, damage, inflammation, fibrosis, cirrhosis, increased risk of cancer, (20% of adults 40-60, Tx is wt loss)
consequence of liver TG accummulation (alcoholic)
liver damage, inflammation, fibrosis, cirrhosis, increased risk of liver cancer
how does glucose become TGs
under high insulin, once liver’s E demands are met, TCA shuts off and Acetly-CoA can be used to make FAs
FA–>3FAs—>TG—>VLDL
insulin inhibits hormone sensitive lipases, increased expression of LPL, increased expression of GLUT 4 on adipocytes and m cells
committed reactant of FA synthesis
malonyl CoA, made in cytosol from Acety CoA
total list of cofactor/coenzymes for FA synthesis
B1 B2 B3 (for NADPH) B5 (FA synthase, malonyl CoA ----> palmitc acid) B7 (to make malonyl CoA from citrate NADPH ATP Malonyl CoA (one per cycle, adds 2 C) Acetyl CoA (initial one bound to synthase)
five mitochondrial precursors for FA synthesis
pyruvate acetyl CoA OAA Citrate Malate
where does FA synthesis occur
cytosol
