BCH2022 Study Guide - Final Guide: Carnitine O-Palmitoyltransferase, Acetyl-Coa, Carnitine
Fatty Acid Oxidation (β-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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