7. Lipid Metabolism 1 Flashcards
Where does fatty acid synthesis primarily occur (organ)?
The liver
Other than the liver (primary), where might fatty acid synthesis occur? (4)
- Adipose tissue
- Brain
- Kidneys
- Lactating mammary glands
What is the most important substrate in fatty acid synthesis?
What enzyme catalyzes this reaction?
Malonyl CoA
Acetyl CoA Carboxylase
What is the rate limiting step of fatty acid synthesis?
Acetyl CoA Carboxylase
Where is Acetyl CoA synthesized?
In the mitochondrial matrix
What two molecules come together to make Citrate?
What enzyme catalyzes this reaction?
Oxaloacetate and Acetyl CoA
Citrate synthase
Why do we need to make Citrate in the first step of fatty acit synthesis?
To get Acetyl CoA out of the mitochondria
Once Citrate is in the cytosol, what enzyme breaks it apart into Oxaloacetate and useful Acetyl CoA?
Citrate Lyase
What two molecules positively regulate Citrate Lyase?
Insulin and glucose (High energy state? Upregulate fatty acid synthesis!)
What two molecules negatively regulate (inhibit) Citrate Lyase?
Poly-Unsaturated Fatty Acids (PUFA)
Leptin (Fullness hormone)
What two molecules positively regulate Acetyl-CoA Carboxylase?
Citrate (earlier step pushes forward)
Insulin (Make that fatty acid, get glucose out of the blood!)
What five molecules negatively regulate Acetyl CoA Carboxylase
- Glucagon
- PUFA
- Epinephrine (scare that fat away!)
- Elevated AMP (low energy? Don’t make fat!)
- Palmitate (end product pushes backwards)
Is Acetyl CoA Carboxylase (ACC) more active by itself, or with its friends as a polymer?
ACC’s active form is as a polymer. (visable under the right kind of microscope)
What does Malonyl CoA inhibit?
Carnitine Acyltransferase - the rate limiting step in Fatty Acid degradation
What form is active Fatty Acid Synthase (FAS) found in?
How many enzyme activities does each complex perform?
What other important protien is present?
- A complex of two identical dimers.
- Each of the complexes has 7 enzyme activities
- Acyl Carrier Protien
What is the ratio of Acetyl CoA to Malonyl CoA in the Palmatate Synthase reaction? (FAS)
1 Acetyl CoA to 7 Malonyl CoA
What are the four steps that get cycled through by FAS?
- Condensation
- Reduction (using NADPH from PPP)
- Dehydration
- Reduction
Does ATP Citrate Lyase get activated or deactivated by phosphorylation?
Activated
(Mnemonic: it likes phosphorous so much, it put three phosphates in its own name!)
Does Acetyl CoA Carboxylase get activated or deactivated by phosphorylation?
ACC is deactivated by phosphorylation
Glucagon likes to phosphorylate things, and since it’s a hungry molecule, it’s not about synthesizing fat.
How is Acetyl CoA Carboxylase affected by a high carb diet?
It is significatly upregulated. More glucose means more fatty acid synthesis, and since ACC is the rate limiting step, it makes sense to make more of that.
What is used as the reducing power for longer chain FA?
NADPH (yet another PPP connection)
What carbon donor is used by Smooth Endoplasmic Reticulum to elongate fatty acids beyond palmitate?
Malonyl CoA
From a biosynthetic standpoint, why is it important that we ingest omega 6 and omega 3 fatty acids?
Human synthases cannot introduce a double bond beyond carbon 9, so they are used to make fatty acids with farther terminal unsaturations.
Linoleic acid (omega 6) is used to make what important biosynthetic precursor?
Arachidonic acid
Linolenic acid (omega 3) is used to make what two important fatty acids?
- Eicosapentanoic acid (EPA)
- Docosahexanoic acid (DHA)