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I HATE FATTY ACIDS!!! (PHASE 3 (beta oxidation)
spiral pathway, multi…
I HATE FATTY ACIDS!!!
PHASE 3 (beta oxidation)
- spiral pathway, multi-enzyme complex
- 2C removed from the -COOH end
- FINAL CLEAVAGE RELEASE: Acetyl CoA, 2C shorter FA-CoA (re-enters spiral)
- energy rich intermediate: NADH + FADH2 (same as glucose)
- final stage: TCA and ETC
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preferred fuels:
- skeletal muscles: rest - fatty acids, active - glucose
- cardiac muscle: FA > ketone bodies > glucose > lactate
- liver: FA
- braine: ketone bodies and glucose ONLY
ketone bodies:
- water soluble
- main ones: beta-hydroxybutarate + acetoacetate
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in starvation, there isn't enough production of oxaloacetate, and therefore acetyl CoA has can't be used in the TCA cycle - instead it forms ketone bodies
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ENERGY YIELD:
- each round: 1x NADH, 1x FADH2, 1x Acetyl CoA
- LAST round: 2x Acetyl CoA (instead of 1)
- formula for number of rounds: (n/2)-1, where n= number of carbons
remember:
- FADH2 = 2ATP
- NADH = 3ATP
- Acetyl CoA = 12ATP
yields 2x ATP more thn glycogen
- when it's stored, it's stored anhydrously
- glycogen stores glucose w water, hense less glucose per store
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CATABOLISM: 3 PHASES
1) activation of FA (cytosol)
2) transport of FA (mitochondria)
3) beta oxidation [successive removal of 2C] -> Acetyl CoA
PHASE 1
- needs ATP 'investment'
- acyl-CoA synthase
- FA + CoASH + ATP -> Fatty acyl-CoA + AMP + PPi
- acyl group: derived from carboxylic acid, without the -OH
PHASE 2
- needs a transporter as it can't freely diffuse
- transporter: carnitine, derivative of lysine
- synthesised in the body
- fatty acylcarnitine exchange!!
- carnitine acyltransferase
- the fatty acyl group binds on carnitine, and when inside the mt it rebinds to CoA-SH to reform fatty acyl-CoA
FATTY ACID SYNTHESIS
PHASE 2) convert AcCoA to Malonyl CoA (activation)
- rate limiting = main regulated phase
- carboxylation rxn
- AcCoA + HCO3- --> Malonyl CoA
enzyme: ACETYL COA CARBOXYLASE [needs biotin]
regulation:
- citrate increases
- malonyl CoA + FA decreases
occurs in 3 stages:
- Acetyl CoA transport
- Acetyl CoA activation
- consecutive 2C addition
PHASE1) uses citrate to facilitate Acetyl CoA out of the mitochondria
- this is bc in the mt, TCA cycle is occurring, if we have enough energy, don't need to produce it so we move AcCoA away so that it won't be used in the TCA cycle and instead can be stored as FA
- uses CITRATE SYNTHASE: removes the CoA-SH group and forms citrate
- citrate goes through the citrate transporter
- transported to the cytoplasm, where it rebinds w CoA-SH by CITRATE LYASE
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PHASE 3) 2C addition
- added to malonyl CoA
- enzyme: FATTY ACID SYNTHASE
- multi enzyme polypeptide
- linear array
- works as a dimer
- growing FA is still connected to enzyme
- occurs in the cytosol
- requires: NADPH (comes from PPP), MALONYL COA, ACETYL COA
- PRODUCT: PALMITATE (16C), uses 8ATP
RECIPROCAL REGULATION OF CATA/ANABOLISM
- starvation: catabolism - epinephrine + glucagon stim
- fed state: anabolism - insulin inhibits catabolism
- malonyl CoA inhibits carnitine acetyltransferase, inihibiting catabolism
appreciate: we need to modify palmitate to utilise the NADPH