Lipids (Lecture 19) Flashcards
where does beta oxidations occur?
mitochondria
what are the energy producing molecules generated by the conversion of fatty acids to acetyl CoA
NADH and FADH2
what are the origins of fatty acids?
uptake from the circulation (as lipoproteins, chylomicrons and VLDL) which is initially from the diet, lipolysis and/or the liver.
lipid storage as lipid droplets (lipolysis to free the FA)
from the plasma membrane, the Lang cycle with phospholipase A1 or A2 will liberate fatty acids.
how are free fatty acids transported into the mitochondria?
fatty acids with a carbon chain larger than 16 carbons cannot cross the inner mitochondrial membrane.
- activation of the fatty acids by CoA via Acyl-Cos Synthetase. an ATP will transfer an AMP onto the FA and will generate PPi–>2Pi. the acyl adenylate produced is a high energy intermediate that allows for the attachment of S-CoA to produce acyl thioester.
- Couling to carnitine via carotene palmitoyl transferase 1 via CPT1. (rate limiting step).
- transit towards the mitochondrial matrix via carnitine-acylcarnitine translocase.
acylcarnitine is taken into the mitochondria matrix via a carnitine carrier protein (anti port exchanges for a molecule of carnitine). Acylcarnitine can be hydrolyzed with the addition of CoA and the enzyme CPT2 to produce acyl CoA. Acyl CoA will then be used as a substrate for beta oxidation and the production of acetyl CoA.
what is the rate limiting step for FA breakdown?
Carnitine palmitoyl transferase 1 (CPT1)
what inhibits the CPT1?
malonyl CoA (a FA)
High malonyl-CoA in the cytosol is present in high energy states, biosynthesis of FA is triggered, thus stopping FA breakdown.
why is AMP added to the FA when getting into the mitochondria?
trap/sequester the FA, as for this renders the molecules impermeable to membranes
why cant we break the carbon bond of C16acyl CoA (palmitoyl CoA) to generate acetyl CoA and energy?
cleaving this bond would produce a completely organic, lipophilic, non-reactive molecule
how to keep palmitoyl CoA when cleaving the c-alpha and c-beta bond?
dehydrogenation to transfer electrons from FADH2, which oxidizes the beta carbon
steps of beta oxidation of saturated FA?
- dehydrogenation (FAD e- acceptor)
- hydration
- dehydrogenation (NAD+ e- acceptor)
- thiolic cleavage via addition of CoA-SH, acetyl CoA is generated
- repeat
link the ETC to beta oxidation of fatty acids
the FADH2 will be part of the ETF (using FAD as a cofactor) to deliver e- to coenzyme Q to generate ATP via the ETC.
total ATP yield from one palmitate
106 ATP
beta oxidation of unsaturated FA
- isomerisation to move the double bond into an even position. (C2)
- hydration
- dehydrogenation
- thiolic cleavage
- repeat
note: no FAD needed (no FADH2 produced, thus 1.5 ATP less)
beta oxidation of a polyunsaturated FA
if there are double bonds on both even and odd FAs: (ex: linoleoyl CoA
- 3 beta oxidations to move the double bonds from C9 and C12 to C3 and C6.
- isomerization with out the generation of FADH2
- 1 cycle of beta oxidation to get rid of the C2 double bond (no more original C9 double bond)
- the original C12 double bond is now located on position 4. After a dehydrogenase reaction that produces FADH2, the molecule will interact with NADPH to move the C4 bond too C3
- isomerization
- double bond is eliminated via 4 cycles of beta oxidation
beta oxidation of odd chained FA
- normal beta oxidation until the last 3 carbons
(the last 3 carbines released as propionyl - CoA)
- proopionyl CoA (3C) will be converted into succinyl-CoA (4C)
this step requires ATP and HCO3 via carboxylase and biotin coenzyme
- the generation of succinyl CoA joins the CAC
