BIOC 503 - LIPID BIOSYNTHESIS

malonyl-CoA

• active molecule because attached to a CoA group

• intermediate in fatty acid biosynthesis

• inhibitor of CAT1 enzyme thus blocking B-oxidation4

• reason why biosynthesis and B-oxidation do NOT happen simultaneously

acetyl-CoA Carboxylase

aka ACC

• rate-limiting enzyme for fatty acid biosynthesis

• require biotin as a cofactor

• 3 subunits enzyme using ATP to male malonyl-CoA from acetyl-CoA

biotin carrier protein

part of ACC enzyme attached to biotin

biotin carboxylase

subunit of ACC using ATP and carbonate to add a carboxy group to biotin

• 1 ATP per 1 malonyl-CoA formation

transcarboxylase

ACC subunit transferring the carboxy group from biotin to acetyl-CoA to make malonyl-CoA

• lead to regeneration of biotin

fatty acid synthase, cytosol

the ___ aka FAS complex is located in the ____

7

the FAS complex is an enzyme complex that has __ subunit

acyl carrier protein

aka ACP

domain on the FAS complex covalently linked to an arm with a thiol group in order to attach to malonyl-CoA

Ketoacyl ACP synthase

aka KS

domain of FAS complex enzyme where acetyl-CoA binds to in the first cycle to prime it, and where the growing fatty acid is transferred as more malonyl-CoA molecules are added

• cysteine residue used to attach to acetyl-CoA originally

FAS fatty acid biosynthesis

1. Acetyl-CoA binds to KS domain and CoA is removed = primed cycle (ONLY happens in the first cycle)

2. Condensation reaction adding acetyl group to malonyl-CoA and releasing CO2 

3. Reduction rxn using NADPH to add -OH hydroxy group to beta C

4. Dehydration rxn taking hydroxy group off so there is a double bond between alpha and beta C releasing water

5. Reduction rxn using NADPH to replace double bond with H atoms, so chain is fully saturated

6. Transfer from ACP to KS domain so ACP now available for new malonyl-CoA molecule binding

Start again from step 2 until palmitic acid is mad eka 16C long

(n/2)-1

number of cycles needed for SYNTHESIZING fatty acids

• n = #C in fatty acids

7

number of cycles needed to synthesize palmitic acid (16C)

carboxyl

In each biosynthesis cycle, 2 carbons are added to the ___ end

condensation, CO2

The end product of biosynthesis has an even number of carbons despite the carbon donor malonyl-CoA having 3 carbons is because it is decarboxylated in the ___ and the extra carbon is released as ___

2

Number of NADPH molecules used per cycle of biosynthesis

1:1

ratio of used ATP to malonyl-CoA produced

reaction of palmitic acid synthesis

1 acetyl-CoA + 7 malonyl-CoA + 7ATP+ 14 NADPH = palmitic acid + 8 CoA + 14 NADP + 7 CO2 + 7 ADP + 6H2O

• 6 H2O instead of 7 because 1 is used to hydrolyze the product off of the enzyme

CO2

# of ___ produced = # of malonyl-CoA used

16

Elongation is the process of making biosynthesized fatty acids longer than palmitic acid aka longer than __ C

elongase

enzyme in the ER and mitochondria using NADPH to add 2 C to the carboxy end of palmitic acid to make it longer

desaturases

enzymes also called mixed-function oxidases in the smooth ER using NADPH and O2 to add double bond to biosynthesized fatty acids

• present in most aerobic organisms

• delta 9 ___ is the most common

polyunsaturated

elongase and desaturase synthesize ___ fatty acids from 2 essential fatty acids: 18:1 omega 6 & 18:3 omega 3

omega

During polyunsaturated fatty acids synthesis, round of desaturation and elongation alternate, as the desaturation enzyme is position specific, so when the elongase add carbon to the carboxyl end, the enzyme position is free for desaturation again. 

The main rule is that the ___ classification is NEVER changing

omega classification

carbon #1 is the one at the END of the hydrocarbon chain, aka the farthest from the carboxy group

insulin

high __ to glucagon ratio aka high levels of __ upregulate ACC activity and thus fatty acid biosynthesis