Fatty acid synthesis Flashcards
When does ketogenesis occur?
Under starvation conditions, when oxaloacetate levels fall, and Acetyl-CoA accumulates because it can’t enter the CAC to become citrate.
Under this conditions too, acetate is converted back to acetyl CoA in the liver.
BIG IDEA: Ketogenesis happens when Acetyl-CoA accumulates, it’s an “over-flow” pathway.
Acetate to Acetyl-CoA reaction and enzyme
1) Acetate + ATP + CoA-SH = Acetyl-CoA + AMP + PPi
2) Acetyl-CoA synthetase
3 ketone bodies
1) Acetone
2) Acetoacetate
3) beta- hydroxybutarate
4) they get transported from liver to other tissues
5) the last two get converted back to Acetyl-CoA outside of the liver
Where does ketogenesis happen?
1) Mitochondria (primarily in the liver)
β-ketoacyl-CoA-transferase/ regulation of ketogenesis
1) Converts beta-hydroxybutyrate to acetyl-CoA
2) ONLY exists in the liver to prevent a futile cycle. One tries to use ketone bodies for energy, other tries to convert them back to acetyl-CoA
Ketogenesis and diabetes
1) tissues are unable to appropiately use glucose
2) ketones bodies are produced in excess (peripherial tissues can’t take them anymore) = ketosis
3) ketoacidosis in diabetes: accumulation of acetoacetate and β-hydroxybutyrate leads to ionization of their carboxyl groups
Importance of Atecyl-CoA
1) Comes from pyruvate (carbohydrate breakdown), fatty acids, it is a fatty acid precursor and a ketone body precursor.
2) Cannot undergo convertion to carbs
Conversion of carbs to fats is UNIDIRECTIONAL
3) It is a central metabolite for many pathways
3 steps of Fatty Acid Biosynthesis and locations
1) Biosynthesis of palmitate (16C) from Acetyl-CoA (cytosol)
2) Elongation of the Chain starting from palmitate (mit and ER)
3) Desaturation (ER)
Differences between fatty acid oxidation and synthesis
Different:
1) enzymes
2) carriers
3) locations
4) regulation
5) stereochemistry of the intermediates
Malonyl-CoA from Acetyl-CoA
1) irreversible ->highly exergonic
2) requires ATP
3) done by Acetyl-CoA carboxylase
Functions of acetyl-CoA carobxylase
1) biotin carrier protein
2) biotin carboxylase
3) transcarboxylase