lecture 7 Flashcards
What does Acetyl - CoA carboxylase catalyse?
Acetyl CoA into Malonyl CoA. This is a key regulatory step
What does Biotin do in the Acetyl- CoA enzyme?
Biotin is a co-enzyme. It is covalently linked to a lysin residue via the ε–amino group
What are the two enzymatic compartments of Acetyl CoA carboxylase?
- Biotin carboxylase
- Transcraboxylase
Description of the E.coli Acetyl CoA carboxylase enzyme
is a multienzyme complex that has 3 protein components:-
1) biotin carboxyl carrier protein (BCCP) 2) biotin carboxylase 3) carboxyltransferase
Description of Acetyl- CoA carboxylase
- ACC is a biotin dependent
- It catalyses the first step of fatty acid biosynthesis
- rate controlling step
What does Lysine chain do in mammalian Acetyl CoA Carboxylase?
linkes to biotin to the protein
Why is lysine important in the mammalian Acetyl CoA carboxylase ?
allows the attached CoA to take up Acetyl - CoA to then form Malonyl CoA
What is the ACC mammalian enzyme found as?
A non functional dimer, must be a polymer to be active
What is the E.Coli Acetyl - CoA carboxylase found as?
- biotin carboxyl carrier protein (BCCP)
- biotin carboxylase
- Carboxyltransferase
How many genes are needed for the ACC e.coli enzyme?
3 different genes
How are E.coli and and mammalian ACC different?
Mammalian ACC comes from the same polypeptide chain
What is significant about Fatty acid synthase?
multiple activities - different combinations in different species
what are the different domains in Fatty acid synthase?
KS,MT,KR,HD,ER,AT,ACP
What are the domains which work together on FAS in bacteria and plants?
KS,MT, KR, HD,ER,AT, ACP - all of them
What are the domains working in yeast?
KS, KR
What are the domains working in vertebrates?
single gene which has all activities
Why are the intermediates for FAS low in concentration in solution?
Intermediates are not released
How does B - ketoacyl ACP synthase (KS domain) attach acetyl?
The cysteine has an SH group which is the priming site
How does the Acyl carrier protein bind its substrate?
Attachment site here is - SH attached to the 4 - phosphopantetheine, linked to serine
How are the gene activities arranged ?
in a X like structure
What does the yeast fatty acid synthase release as a product =?
- released as palmitoyl - CoA
- the palmitate is transacylated onto CoA from ACP rather than hydrolysed to free fatty acid
What does the bacterial/plant enzyme fatty acid synthase release a a product?
- 20% is palmitoyl -Coa or palmito - ACP
- 70% is vaccinate - CoA
Where is the Acetyl CoA synthesised?
the mitochondria
What is the overall output per Acetyl CoA?
Utilisation of 2 ATP with conversion of one NADH to NADPH
With transfer of 1 CO2 from the mitochondrion to the cytosol
OR
Utilisation of 1 ATP and
No net change in NAD+/NADH
Where is the NADPH produced that is needed for the FA synthesis?
The pentose phosphate pathway
What happens in the mitochondria?
High [NADH]/[NAD+]
this is due to the oxidation of fatty acids, amino acids, pyruvate and acetyl-CoA which occurs in the mitochondria
What value is high in the cytosol?
High [NADPH]/[NADP+]
Hepatocyte value ~ 75.
This favours the reductive reactions of F.A. synthesis
What value is low in the cytosol?
Low [NADH]/[NAD+] typically 8 x 10-4
So NAD+-dependant oxidative catabolism of glucose can occur in the same compartment, at the same time, as F.A. synthesis
What is cytosolic NADPH generated by ?
Malic enzyme and pentose phosphate pathway
Which catalytic activity of the mammalian fatty acid synthase determines the chain length of the fatty acid product?
Ketoacyl- ACP synthase
