Lecture 28/29: Lipid metabolism Flashcards
Major step in phase one of FA synthesis
Cytosolic entry of Acetyl CoA
Its made in the mitochondrial matrix but needed in cytoplasm
Major step in phase two of FA synthesis
Generation of Malonyl CoA
Acetyl CoA is carboxylated to malonyl CoA- Most important substrate in FA synthesis
Rate limiting step
Major step in phase three of FA synthesis
FA chain formation
Fatty acid synthase catalyzes 7 reactions that incorporate Acetyl CoA and Malonyl CoA into Palmitate
Steps in transport of Acetyl CoA from mitochondria to cytoplasm
- Acetyl CoA + Oxaloacetate makes Citrate
- Transport of citrate from mitochondria to cytosol
- Citrate converted back to Acetyl CoA and OAA (citrate lyase catalyzes)
- Acetyl CoA used in FA syntheses, OAA reduced to malate
Two mechanisms for regeneration of OAA after it is reduced to malate in cytosol
- Malate transported back into mitochondria via malate/a-ketoglutarate transporter, then oxidized to OAA by malate dehydrogenase
- Cytosolic malate converted to pyruvate which is transported to mitochondria and carboxylated to OAA by pyruvate carboxylase
Acetyl CoA carboxylase (ACC)
Catalyzes Acetyl CoA–>Malonyl CoA
- Adds CO2 to Acetyl CoA
- Rate limiting step in FA synthesis
- Uses ATP and Biotin
ACC structural forms and active state
Dimeric- inactive
Polymeric- active
How does Malonyl CoA help regulate FA pathway
Inhibits Carnitine Acyltransferase (Rate limiting enzyme in FA degradation)
Prevents FA synthesis and degradation from occurring simultaneously
What substrates are required for palmitate synthesis
1 Acetyl CoA
7 Malonyl CoA
14 NADPH
14 H+
What are the substrates for the initial reaction to begin forming palmitate
1 Acetyl CoA
1 Malonyl CoA
2 NADPH
Then 1 Malonyl CoA and 2 NADPH are added 6x more
ATP citrate lyase function/regulation
Converts Citrate to Acetyl CoA and OAA
Stimulated by phosphorylation
Gene expression induced by glucose/insulin and counteracted by PUFAs (polyunsaturated fatty acids) and Leptin
Allosteric regulation of ACC (Acetyl CoA Carboxylase)
\+ Citrate \+ Insulin - Glucagon - High AMP levels - Epinephrine - PUFA - Long chain fatty acids (palmitate)
Phosphorylation/activation state of ACC- what molecules regulate using what enzymes
Inactivated by phosphorylation Insulin + via activation of PP Epi - via PKA Glucagon - via PKA AMP - via AMP kinase
Gene expression of ACC is upregulated via
High carb/low fat diet
Presence of phosphorylated sugars has what effect on Fatty acid synthase (FAS)
Increased activity
Induction/repression of transcription of FAS is affected by
Insulin/glucocorticoid hormones ++ High carb/low fat ++ High fat diet -- Starvation -- High PUFA --
Where is palmitate converted into longer chain
Smooth ER or mitochondria
Fatty acid synthesis occurs primarily where, but also
Primarily in liver
Also in adipose tissue, brain, kidneys, lactating mammary glands
When palmitate is converted into a longer chain, what molecules donate carbons in the SER vs the Mitochondrial pathway of palmitate elongation
SER- Malonyl CoA is carbon donor
Mitochondria- Acetyl CoA is carbon donor
T or F: Brain cells need longer chain fatty acids
True, Palmitate is lengthened 2 carbons at a time, using NADPH as reducing power
T or F: FA with double bond beyond carbon 11-12 cannot be synthesized
False
FA with double bond beyond carbon 9 and 10 cannot be synthesized
Where does introduction of double bonds (desaturation) occur for fatty acids
In the smooth ER, using NADH or NADPH and oxygen, catalyzed by Acyl CoA Desaturases
Can humans synthesize Omega 3 and Omega 6 fatty acids
No, they must be incorporated into diet
What is used to make arachidonic, docosahexanoic and eicosapentanoic acid
Linoleic acid
