Lipids 2 Flashcards
How is Acetyl-CoA exported from Mito matrix?
combines w/ OAA to form citrate which can be transported across membrane; in cytosol citrate splits to give acetyl-CoA again and OAA; OAA–> malate (malate dehydrogenase:using up a NADH) and then malate –> pyruvate (malic enzyme: producing NADPH) pyruvate is transported into matrix by translocase enzyme
Citric Cleavage Pathway and Cell Levels of Citrate
provides acetyl-CoA and NADPH to cytoplasm for synthesis of FA’s; High cytoplasmic levels of citrate indicate that acetyl-CoA is being pushed out of mito so the CAC is not able to process all of it from the breakdown of carbs, glycolysis slows down and FA synthesis ramps up!
Committed Step for FA synthesis, where does this occur
acetyl-CoA –> Malonyl-CoA (acetyl-CoA carboxylase; requires ATP and CO2 input) occurs in cytosol–keeps synthesis SEPARATE from beta-oxidation
Only producers of NADPH
Malic enzyme and PPP–FA synthesis needs NADPH!
Energy Requirements to make 1 molecule of palmitic acid
8 acetyl-CoA, 7 ATP, 14 NADPH–whole rxn sequence is 7 rounds
Where do FA’s get elongated? Which end is elongated?
Endoplasmic reticulum (process similar to FA synthesis – carbon donor is malonyl-CoA) and mitochondria (similar to reverse beta-oxidation – carbon donor is acetyl-CoA); FA’s elongated on the carboxyl end of molecule not omega end–important for synthesis of membrane lipids
How do FA’s get desaturated?
In ER: requires p450 monooxygenase system, begins by introducing a double bond at carbon 9
Important Features of Lipid Droplet
- surrounded by phospholipid monolayer
- covered w/ structural protein–perilipin
- bind enzymes required for TAG synthesis (acyltransferases) and degradation (lipases)
Where does Glycerol come from for TAG synthesis
in well fed state it is produced from DHAP in glycolysis
Fat (TAG) Synthesis and Committed Step
activated acyl-CoA molecules are sequentially esterfied to glycerol by acyl-transferases;
acyl-CoA + diacylglycerol –> TAG (acyl-CoA:diacylglycerol acyltransferase [DGAT]) only committed step
3 Signals that Regulate Fat synthesis and degradation
- Nutritional Status (insulin vs. glucagon)
- Energy Status (ATP vs. AMP)
- Presence of Lipids
Insulin induces what enzymes for FA synthesis
acetyl-CoA carboxylase, FA synthase, malic enzyme, glucose-6-phosphate dehydrogenase (NADPH production from PPP)
Citrate activates what enzymes
FA synthase and acetyl-CoA carboxylase–indicator of acetyl-CoA surplus
Starvation State and fat synthesis
levels of cAMP rise along w/ activity of PKA which inactivates acetyl-CoA carboxylase shutting down FA synthesis at regulated step
Regulation by Malonyl-CoA
inhibits FA degradation–does this by inhibiting main regulated step of FA degradation which is import of FA’s into mito matrix (CPTI enzyme)
