Lipids Biosynthesis (mini-test 1 AND 2) Flashcards
Lipids are made from just 2 precursor molecules. What are they?
1) FAs
2) isoprene
Where are lipids located?
-cytoplasm of liver
-adipose tissue
-kidney
-brain
-breast
-muscle
What materials are needed to make fats?
-acetyl CoA which will be converted to malonyl CoA with acetyl CoA carboxylase
-ATP
-NADPH
-CO2
-vitamin B7/biotin
Where is acetyl CoA made?
in mitochondria
Where is malonyl CoA made?
in cytoplasm
What is step 1a of lipid biosynthesis?
-citrate shuttle is used for exporting acetyl CoA from mitochondria to cytoplasm
-this generates NADPH with malic enzyme
What are the 2 major sources of NADPH?
1) malic enzyme from citrate shuttle
2) PPP
What is step 1b of lipid biosynthesis?
test q
-acetyl CoA is the major substrate to build up FAs
-acetyl CoA, ATP, CO2, biotin/vitamin B7, and acetyl CoA carboxylase undergo a reaction to make malonyl CoA and ADP
-this is the rate limiting step of FA biosynthesis
What is the most important enzyme of biochem 2?
acetyl CoA carboxylase
Which enzyme converts acetyl CoA to malonyl CoA?
acetyl CoA carboxylase
What 3 carboxylase enzymes have we talked about that all require ABC?
1) pyruvate carboxylase (RLE in gluconeogenesis, converts pyruvate to OAA)
2) propionyl CoA carboxylase (converts propionyl CoA to MMCoA)
3) acetyl CoA carboxylase (converts acetyl CoA to malonyl CoA)
3 enzymes require biotin: pyruvate carboxylase, propionyl CoA carboxylase, and acetyl CoA carboxylase. So when theres a biotin deficiency, what happens?
-accumulates pyruvate, propionyl CoA, and acetyl CoA
-eventually will cause acidosis bc they’re all acidic
-causes gray mucus
-long term will cause peripheral neuropathy, hair loss, and pale skin
Which step of FA biosynthesis is reverse steps of beta oxidation?
step 2 of FA biosynthesis
What is step 2 of FA biosynthesis?
-repetitive steps catalyzed by FA synthase (also known as fatty acyl synthase)
-an enzyme complex is used with 7+ catalytic activities
In beta oxidation, you break from the __________ end, but in FA synthesis, you build from the _________ end
carboxyl, methyl or omega
What is step 3 of FA biosynthesis?
-priming of fatty acyl synthase/acyl synthase
-2 carbons from the acetyl CoA is transferred to the KAAS site to charge the enzyme
-the first 2 carbons added are derived from acetyl CoA and become the last 2 carbons of the complete FA
-only the acid will be linked to the synthase
-fatty acyl chain will elongate and this will undergo 4 reactions
What is step 3A of FA biosynthesis?
condensation rxn
-malonyl CoA is transferred to the ACP binding site
-malonyl CoA condenses with acetyl chain on KAAS, liberating carbon dioxide
-the elongating acyl chain moves back to ACP and creates ketoacyl-ACP and will release CO2
What is step 3B of FA biosynthesis?
reduction rxn
-ketoacyl-ACP is reduced by ketoacyl-ACP reductase using NADPH to generate beta hydroxyacyl-ACP
What is step 3C of FA biosynthesis?
dehydration rxn
-hydroxyacyl-ACP dehydratase removes water from the beta and alpha carbon to create a double bond between them in enoyl-ACP
What is step 3D of FA biosynthesis?
reduction rxn
-enoyl-ACP reductase reduces the double bond to create a saturated fatty acyl chain using NADPH
-the fatty acyl now is longer by 2 carbons and is transferred back to KAAS site
-the next malonyl CoA is bound at the now vacant ACP site so the process can be repeated
-the cycle will continue until the fatty acyl chain is 16 carbons long (palmitate), anything longer requires a seperate elongation system
How many malonyl CoA and acetyl CoAs are needed to synthesis palmitate?
7 malonyl CoA (for elongation) and 1 acetyl CoA (for initial charging of FA synthase)
What 3 enzymes create NADPH?
1) G6P DH
2) 6 phosphogluconate DH
3) malic enzyme
What is the most common product of fatty acyl synthase?
palmitate 16:0
How many NADPHs are used to make palmitate?
14 NADPH (2 per cycle, so 7 cycles used 14)
What does malonyl CoA require to be synthesized?
-acetyl CoA
-ATP
-biotin
-CO2
CO2 is a byproduct of which reaction in FA biosynthesis?
condensation rxn (step 3A)
Where does FA synthesis occur?
in cytoplasm