BCH2022 Study Guide - Final Guide: Carnitine O-Palmitoyltransferase, Acetyl-Coa, Carnitine

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Fatty Acid Oxidation -oxidation)
Location: mitochondrial matrix of all tissues (except brain)
Function: to produce energy
o Catabolic process
o To produce acetyl-CoA which enters citric acid cycle
o And NADH and FADH2: co-enzymes used in electron transport chain
Lipids yield more ATP per molecule than glucose
o More important long term energy source
Fatty acid + 8 CoA + 7 NAD+ + 7 FAD 8 Acetyl-CoA + 7 NADH + H+ +
7FADH2
-ve ∆G’˚
^ equation for C16 (e.g. Palmitic acid).
o 7 cycles of β-oxidation forms 8 acetyl CoA
Prior β-oxidation: Activation of fatty acid
Occurs in cytoplasm
Enzyme: fatty acyl-CoA synthetase
Cofactors: CoA, ATP
o Produces AMP+ PPi
Fatty Acid Transport Acyl-Carnitine Transport
Required for entry of acetyl-CoA into mitochondria via carnitine shuttle
o Due to negative charge
Carnitine: produced in liver and kidneys from lysine and methionine
Carnitine acyltransferase I
o Located: outer mitochondrial membrane
Carnitine acyltransferase II
o Located on inner membrane
Small chain fatty acids don’t require carnitine, small enough to absorb/move
through membrane
Saturated Fatty Acids (OHOT)
1. (Step 1) Oxidation (dehydration)
Cofactor: FAD: prosthetic group of enzyme accepts election
FADH2
Enzyme: Acyl-CoA dehydrogenase
2. Hydration
Water added to double bond
Enzyme: enoyl-CoA hydratase
3. Oxidation
Cofactor: NAD+
o Accepts 2H+ NADH
Enzyme: hydroxyacyl-CoA Dehydrogenase
4. Thiolysis (cleavage)
Requires reduced CoA (CoASH
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o Cuts off carbon back bone cleaves off acetyl-CoA (two
carbons shorter)
Enzyme: thiolase
Energy Yield Per Cycle
1 FADH2 1.5 ATP
1 NADH 2.5 ATP
o Total 4 ATP
1 Acetyl CoA to CAC
o 3 NADH x 2.5 ATP / NADH 7.5 AT
Requires 3 cycles
o 1 FADH 2 1.5 ATP
o 1 GTP 1 ATP
Total 10 ATP
E.g. ATP yield of palmitate (C16)
o 2 ATP required to activate fatty acids for mobilization into
mitochondria
o 7 FADH2 = 10.5 ATP
o 7 NADH = 17.5 ATP
o 8 acetyl CoA = 80 ATP
Net yield: 106
Monosaturated Fatty Acids
Need to break double bond in CIS to a trans bond
Fats are good fuel for endurance events, not springs
Fate of acetyl Co-A
Citric acid cycle
o Entry of acetyl-CoA into CAC requires oxaloacetate
When oxaloacetate is depleted, acetyl-CoA is converted into
ketone bodies
Frees coenzyme A for β-oxidation
Ketone bodies
Comparing Energy Stores
Carbohydrates
Characteristic
Fats
Skeletal muscle
Stored in
Adipose tissue
Hydrates
Stored in … form
Anhydrous
< 1 day
Store … of energy
Weeks
Soluble
… in blood
Insoluble
Cytosol and mitochondria
Oxidised in …
Mitochondria
Anaerobically/aerobically
Produce ATP…
Aerobically
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Formation of Ketone Bodies (Ketogenesis)
Location: liver mitochondria
Formation of ketone bodies: β-hydroxybutyrate, acetoacetate and acetone
o Formed from excess acetyl-CoA produced by β-oxidation
Occurs: after glycogen stores are exhausted in starvation
Function: ketone bodies oxidised by other tissues (cardiac and skeletal
muscle) for energy
Reverse reaction β-ketoacyl-CoA transferase occurs outside liver
During fasting
o Low glucose/insulin
o Body uses fats as energy source
Liver converts excess fatty acis to keton bodies increase in
β-hydroxybutyrate and acetoacetate
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