BB ch 17

Fatty Acid Oxidation

The metabolic process that degrades fatty acids to acetyl-CoA, NADH, and FADH2 via β-oxidation.

Triacylglycerol (TAG)

A glycerol molecule esterified to three fatty acids; major dietary and storage lipid.

Energy Density of Fat

Fatty acids yield ~37 kJ g⁻¹ because their carbons are highly reduced and non-hydrated.

Migratory Bird Fat Loading

Birds store up to 70 % body weight as TAGs to power long flights.

Glucagon

Pancreatic hormone that triggers adipose lipolysis during low blood glucose.

Epinephrine

Adrenal hormone that stimulates TAG breakdown via β-adrenergic signaling.

ACTH

Adrenocorticotropic hormone; promotes lipolysis in adipose tissue.

Adipose Tissue

Specialized tissue storing TAGs in lipid droplets for energy release.

Bile Salts

Amphipathic molecules from gallbladder that emulsify dietary fats into micelles.

Emulsification

Process where bile salts disperse fats into small droplets, increasing lipase access.

Pancreatic Lipase

Enzyme that hydrolyzes TAGs at C-1 and C-3 positions in the intestine.

Intestinal Lipase

Enzyme that removes the remaining fatty acid at C-2 of monoacylglycerols.

Monoacylglycerol

Glycerol esterified to one fatty acid; intestinal hydrolysis intermediate.

Chylomicron

TAG-rich lipoprotein particle that transports dietary lipids via lymph and blood.

Apolipoprotein B-48

Structural protein on chylomicrons that targets them for secretion.

Apolipoprotein C-II

Chylomicron surface protein that activates lipoprotein lipase in capillaries.

Apolipoprotein C-III

Chylomicron protein that modulates lipid metabolism signaling.

Lipoprotein Lipase

Capillary enzyme that releases free fatty acids from circulating chylomicrons.

Perilipin

Lipid-droplet coating protein; phosphorylation allows hormone-sensitive lipase access.

Hormone-Sensitive Lipase

Adipocyte enzyme that hydrolyzes stored TAGs when activated by PKA.

Serum Albumin

Blood protein that transports non-esterified fatty acids to tissues.

Glycerol Entry to Glycolysis

Glycerol is phosphorylated to glycerol-3-phosphate, then oxidized to DHAP.

Knoop Two-Carbon Hypothesis

Historic proposal that fatty acids are degraded by removing 2-carbon units.

β-Oxidation

Cyclic pathway that oxidizes fatty-acyl-CoA at the β-carbon, releasing acetyl-CoA.

Acyl-CoA Synthetase

Enzyme that activates fatty acids to fatty-acyl-CoA using ATP → AMP + PPi.

Acyl-Adenylate Intermediate

Mixed anhydride formed during fatty-acid activation before CoA attack.

Pyrophosphate Hydrolysis

PPi → 2 Pi reaction that drives fatty-acid activation irreversibly forward.

Fatty-Acyl-CoA

Thioester product that enters β-oxidation or mitochondrial transport.

Carnitine

Quaternary amine that shuttles long-chain acyl groups into mitochondria.

Carnitine Acyltransferase I

Outer-membrane enzyme converting acyl-CoA to acyl-carnitine; inhibited by malonyl-CoA.

Carnitine Acyltransferase II

Matrix enzyme that regenerates acyl-CoA from acyl-carnitine.

Acyl-Carnitine/Carnitine Transporter

Inner-membrane antiporter exchanging acyl-carnitine for free carnitine.

Malonyl-CoA

First committed intermediate of fatty-acid synthesis; inhibits CAT I to prevent futile cycling.

Stage 1 of Fatty-Acid Oxidation

β-Oxidation converts long-chain fatty acids to acetyl-CoA units.

Stage 2 of Fatty-Acid Oxidation

Citric acid cycle oxidizes acetyl-CoA to CO₂, producing NADH/FADH₂.

Stage 3 of Fatty-Acid Oxidation

Electron transport/OXPHOS converts NADH/FADH₂ energy into ATP.

Acyl-CoA Dehydrogenase

First β-oxidation enzyme; introduces trans-Δ² double bond, reducing FAD to FADH₂.

Enoyl-CoA Hydratase

Second β-oxidation enzyme adding H₂O across double bond to form L-β-hydroxyacyl-CoA.

β-Hydroxyacyl-CoA Dehydrogenase

Third β-oxidation enzyme oxidizing the β-OH to keto, generating NADH.

Thiolase (β-Ketothiolase)

Fourth β-oxidation enzyme cleaving β-ketoacyl-CoA, releasing acetyl-CoA.

FADH₂ Yield per Cycle

Each β-oxidation round forms one FADH₂ worth 1.5 ATP.

NADH Yield per Cycle

Each β-oxidation round forms one NADH worth 2.5 ATP.

Palmitate ATP Yield

Complete oxidation of palmitoyl-CoA generates about 108 ATP equivalents.

Metabolic Water

Water formed during oxidation of fuels; significant during fat catabolism.

Desert Animal Hydration

Species like camels rely on fat oxidation to generate metabolic water.

Enoyl-CoA Isomerase

Auxiliary enzyme converting cis-Δ³ acyl-CoA to trans-Δ² for unsaturated FA oxidation.

2,4-Dienoyl-CoA Reductase

NADPH-dependent enzyme enabling β-oxidation of polyunsaturated fatty acids.

Odd-Chain Fatty Acid Oxidation

β-Oxidation that ends with propionyl-CoA instead of acetyl-CoA.

Propionyl-CoA

Three-carbon CoA ester processed to succinyl-CoA for entry into TCA cycle.

Propionyl-CoA Carboxylase

Biotin-dependent enzyme converting propionyl-CoA to D-methylmalonyl-CoA.

Methylmalonyl-CoA Epimerase

Enzyme that converts D- to L-methylmalonyl-CoA.

Methylmalonyl-CoA Mutase

Vitamin B₁₂-dependent enzyme rearranging L-methylmalonyl-CoA to succinyl-CoA.

Acetyl-CoA Carboxylase (ACC)

Rate-limiting enzyme of fatty-acid synthesis; produces malonyl-CoA.

β-Oxidation Downregulation

High carbohydrate elevates malonyl-CoA, inhibiting CAT I and reducing fat breakdown.

Seed TAG Mobilization

Germinating plants convert stored TAGs to sucrose via β-oxidation and glyoxylate cycle.

Ketone Bodies

Water-soluble fuels—acetoacetate, β-hydroxybutyrate, and acetone—formed from excess acetyl-CoA.

Acetoacetate

Primary ketone body; can be reduced to β-hydroxybutyrate or decarboxylated to acetone.

β-Hydroxybutyrate

Reduced ketone body that carries more energy than acetoacetate.

Acetone

Volatile ketone; produced non-enzymatically from acetoacetate, exhaled in diabetes/starvation.

Ketogenesis

Mitochondrial liver pathway condensing acetyl-CoA into ketone bodies.

Diabetic Ketoacidosis

Dangerous accumulation of ketone bodies in untreated type I diabetes.

Oxaloacetate Depletion

Withdrawal for gluconeogenesis slowing TCA cycle and diverting acetyl-CoA to ketogenesis.

3-Ketoacyl-CoA Transferase (SCOT)

Extrahepatic enzyme converting acetoacetate to acetoacetyl-CoA; absent in liver.

D-β-Hydroxybutyrate Dehydrogenase

Enzyme oxidizing β-hydroxybutyrate to acetoacetate, producing NADH.

Succinyl-CoA:Acetoacetate CoA Transferase

Transfers CoA from succinyl-CoA to acetoacetate during ketone utilization.

Thiolase (Ketone Utilization)

Splits acetoacetyl-CoA into two acetyl-CoA molecules for energy.

ATP per NADH

Mitochondrial oxidative phosphorylation typically yields ~2.5 ATP per NADH oxidized.

ATP per FADH₂

OXPHOS generally yields ~1.5 ATP per FADH₂ oxidized.

Mixed Micelle

Aggregation of bile salts and lipid digestion products aiding intestinal absorption.

Dietary Fat Digestion

Bile salts, pancreatic lipase, and intestinal enzymes break TAGs into absorbable units.

Small Intestine Absorption

Enterocytes uptake fatty acids/monoacylglycerols and re-esterify them to TAGs.

Lymphatic Transport

Chylomicrons travel via lymph before entering bloodstream at thoracic duct.

Adenylyl Cyclase

Membrane enzyme producing cAMP from ATP upon hormone binding.

cAMP

Second messenger activating PKA during lipolytic signaling.

Protein Kinase A (PKA)

cAMP-dependent kinase phosphorylating perilipin and hormone-sensitive lipase.

Fatty Acid Transporter

Membrane protein facilitating cellular uptake of free fatty acids.

Citric Acid Cycle

Central metabolic pathway oxidizing acetyl-CoA to CO₂, producing NADH/FADH₂.

Respiratory Chain

Series of mitochondrial complexes transferring electrons to O₂ and pumping protons.

L-β-Hydroxyacyl-CoA

Stereospecific product of enoyl-CoA hydratase step in β-oxidation.

β-Carbon (Cβ)

Second carbon from carboxyl end; site of oxidation in β-oxidation.

α-Carbon (Cα)

Carbon adjacent to carboxyl group; forms bond cleaved by thiolase.

Trans-Δ²-Enoyl-CoA

Intermediate with double bond between C² and C³ in β-oxidation.

Cis-Δ³ Double Bond

Unsaturated bond position that blocks normal β-oxidation until isomerized.

Trans-Δ², Cis-Δ⁴-Dienoyl-CoA

Problematic intermediate in polyunsaturated FA oxidation requiring reductase action.

Acyltransferase

General enzyme class moving acyl groups between molecules.

Stored Fuel in 70 kg Human

Approx. 555 MJ as fat, 102 MJ as muscle protein, 3 MJ as glycogen & glucose.

Protein as Fuel

Muscle protein provides ~17 kJ g⁻¹ when catabolized for energy.

Glycogen Energy Density

Glycogen yields ~16 kJ g⁻¹ of dry weight energy.

Glucose in Extracellular Fluid

Readily available but limited (~20 g) fuel reserve.

Long-Chain Fatty Acid (>14C)

Needs carnitine shuttle to enter mitochondrial matrix.

Short-Chain Fatty Acid

(<14C) diffuses directly into mitochondrial matrix without carnitine.

TMAO (Trimethylamine-N-oxide)

Carnitine-derived metabolite linked to atherosclerosis.

AMP Formation in Activation

ATP is converted to AMP; counts as 2 ATP equivalents consumed.

Mitochondrial Matrix

Compartment where β-oxidation, TCA cycle, and ketogenesis occur.

Inner Mitochondrial Membrane

Barrier requiring transporters such as the acyl-carnitine exchanger.

PPi Hydrolysis ΔG°′

~−19 kJ mol⁻¹; drives fatty-acid activation exergonically.

Acyl-CoA Activation Cost

Two high-energy phosphate bonds (ATP→AMP+PPi) consumed per fatty acid.

Crotonase

Common name for enoyl-CoA hydratase.

Hydride Transfer to FAD

Mechanism step in acyl-CoA dehydrogenase creating FADH₂.

NADPH Requirement

2,4-Dienoyl-CoA reductase uses NADPH to reduce conjugated double bonds.