fatty acid degradation (b-oxidation)

Activation of Fatty Acids

Fatty acid + ATP → Fatty‑acyl‑CoA + AMP + PPᵢ, catalyzed by Acyl‑CoA synthetase.

Carnitine Shuttle

Transport mechanism for long-chain fatty acids across the mitochondrial membrane involving CPT-I, Translocase, and CPT-II.

Products of β-Oxidation

Each cycle of β-oxidation produces one Acetyl-CoA, one NADH, and one FADH₂.

CPT-I Inhibition

CPT-I is inhibited by malonyl-CoA, affecting fatty acid degradation.

Hormonal Effect on β-Oxidation

Insulin decreases CPT-I activity while glucagon and epinephrine increases fatty acid oxidation.

Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCAD)

Condition that leads to hypoketotic hypoglycemia after fasting due to a defect in fatty acid degradation.

Acetyl-CoA from Odd-Chain Fatty Acids

Odd-chain fatty acids yield propionyl-CoA, which can be converted to succinyl-CoA for energy production.

Energy Yield from Palmitate

The total ATP yield from a saturated fatty acid like palmitate includes ATP from β-oxidation and TCA cycle.

L-Hydroxy Isomer

The hydration step in β-oxidation always yields the L-hydroxy isoform.

High-Energy Phosphates in Activation Step

The activation step utilizes two high-energy phosphates by converting ATP to AMP.

Activation happens where

cytosol

activation equation

Fatty acid + ATP → Fatty‑acyl‑CoA + AMP + PPᵢ

activation catalyzed by

acetyl-coa synthetase

why amp?

The reaction effectively uses two high‑energy phosphates, “charging” the fatty acid for later oxidation.

carnitite shuttle

used to transport across the inner mitochondrial membrane

CPT‑I (outer membrane)

transfers the acyl group from CoA to carnitine, forming acyl‑carnitine

Translocase

swaps acyl‑carnitine for free carnitine across the inner membrane

CPT‑II (inner membrane)

 re‑attaches CoA, regenerating acyl‑CoA inside the matrix.

Short‑chain/medium‑chain FA

• can cross the membrane directly as CoA‑esters, bypassing the shuttle.

steps of the repeating b-oxidation cycle in the matrix

oxidation, hydration, oxidation, thiolysis

oxidation (step 1) enzyme

Acyl‑CoA dehydrogenase

hydration enzyme

Enoyl‑CoA hydratase

oxidation (step 3) enzyme

3‑Hydroxyacyl‑CoA dehydrogenase

thiolysis enzyme

β‑ketoacyl‑CoA thiolase

oxidation (step 1) reaction

R‑CH₂‑CH₂‑CO‑SCoA → trans‑Δ²‑enoyl‑CoA + FADH₂

hydration reaction

trans‑Δ²‑enoyl‑CoA + H₂O → L‑hydroxyacyl‑CoA

oxidation (part 3) reaction

L‑hydroxyacyl‑CoA → 3‑ketoacyl‑CoA + NADH

thiolysis reaction

3‑ketoacyl‑CoA + CoA‑SH → acetyl‑CoA + shortened acyl‑CoA (n‑2)

the _ step always yields the L-hydroxy isomer

hydration

---

__ enters the TCA cycle

acetyl coa

net atp

106

Odd‑chain fatty acids produce one propionyl‑CoA in the final round, which is converted to

succinyl coa

key regulatory point

CPT-1

CPT-1 is inhibited by

malonyl coa

malonyl coa

the first product of fatty acid synthesis

insulin decreases __

CPT-1 activity and therefore less b-oxidation

Glucagon/epinephrine increase __

fatty acid oxidation

Carnitine transport defects

accumulation of fatty acids, muscle weakness, cardiomyopathy.