FA Synth

Question 1

General

Answer 1

FA synth is very costly, occurs in cytoplasm of liver
FA to TAG exported for storage
FA is heavily reduced via NADPH

Question 2

Overview

Answer 2

Primary carbon source = Glucose. Recipricol control by ins/glucagon. Insulin increases glycolysis, pyruvate, and citrate production

TCA cycle produces citrate from glycolytic carbon, citrate exported to cytosol and cleaved to OAA and acetyl CoA for lipid synth (liver only)

Question 3

FA Source and rqrs

Answer 3

Source = Dietary carbs, excess protein, carbon from citrate

Process: Increased acetyl coa blocks PDH, Pyr carboxylated to OAA to citrate, IDH inhib; citrate exported and cleaved via citrate lyase

Question 4

Substrate 1

Answer 4

cytosolic acetyl CoA created from citrate exported via shuttle, cleaved via citrate lyase with ATP used and CoASH added

Question 5

Coenzyme for FA synth

Answer 5

NADPH

3 production paths (2 from HMP and 1 from Malic enzyme)

Question 6

Also essential for FA synth

Answer 6

ATP and Biotin

Question 7

ATP functions in FA synth

Answer 7

1. Cleavage of stable citrate to OAA and Acetyl CoA (cytosolic CoASH rqrd, IDH inhib permits citrate export)
2. Carboxylation of Acetyl CoA by Acetyl CoA carboxylase to malonyl CoA (commitment step). Biotin (Vit H) binds CO2 in schiff base (def = decreased FA synth)

Question 8

Acetyl CoA Carboxylase

Answer 8

Allosteric Regulation
Sole regulator, polymerization = active and favored by high citrate

Induced by high insulin
Inhib by phosphorylation via AMP Kinase and Palmitoyl CoA (feedback inhib)
Act by increased ATP and citrate

Question 9

Fatty Acid Synthase

Answer 9

7 enzyme functions x2 with:

Covalently bound phosphopantetheine (Vit B5) bound to acyl carrier protein (ACP)
Malonyl CoA and ACP interact, CoASH released
Thioester bond btwn malonyl and -SH
ACP fx = hold growing acyl groups

Question 10

Synthesis

Answer 10

1. Acetyl added to ACP-SH
2. Joins with other Cys-SH
3. Malonyl added to ACP-SH
4. Acetyl and malonyl condense (4C keto-acyl moves to ACP; CO2 released)
5. NADPH reduces keto group
6. Dehyd to double bond
7. NADPH reduces DB
8. Repeat

Question 11

Stoic of process (eg Palm synth 16C)

Answer 11

Acetyl CoA + 7 Malonyl CoA +14 NADPH = Palmitate + 7 CO2 + 8 CoASH - 7 ATP

Acetyl CoA carboxylase rqrs ATP

Question 12

FA synth exceptions

Answer 12

18:2 Linoleic acid and 18:3 linolenic acid = polyunsats
Mod rqrs lengthening and desat in ER

Def = dermititis and poor wound heal

Question 13

FA to TAG

Answer 13

After thiolysis, FAs activated by CoA
Liver and Adipocyte: esterfied to glycerol 3P (source = in situ glycolysis and salvage)
Liver TAGs exp via plasma VLDLs w/ ApoB100

Question 14

Arrival of VLDL at Adipocyte

Answer 14

TAG hydrolyzed by LPL, FA enter and activated by CoASH, esterfied and stored as TAG. LPL attched to cap wall and activated by ApoCII

Only occurs in well fed state