Citric Acid Cycle Overview and Key Concepts

Citric Acid Cycle (CAC)

A cyclic pathway in the mitochondrial matrix that oxidizes acetyl-CoA to CO2, producing NADH, FADH2, and GTP for ATP synthesis.

Amphibolic Pathway

A pathway that can function in both anabolic and catabolic processes, depending on the cell's needs.

Anaplerotic Reactions

Reactions that replenish intermediates of the CAC when they are used in biosynthetic processes.

Citrate Synthase

Enzyme catalyzing the condensation of oxaloacetate and acetyl-CoA to form citrate. Irreversible and regulated.

Aconitase

Catalyzes isomerization of citrate to isocitrate by converting a tertiary alcohol to a secondary alcohol.

Isocitrate Dehydrogenase

Catalyzes oxidative decarboxylation of isocitrate to alpha-ketoglutarate, producing NADH and CO2. Regulated.

alpha-Ketoglutarate Dehydrogenase

Catalyzes oxidative decarboxylation of alpha-KG to succinyl-CoA, producing NADH and CO2. Regulated.

Succinyl-CoA Synthetase

Converts succinyl-CoA to succinate, producing GTP via substrate-level phosphorylation.

Succinate Dehydrogenase

Catalyzes oxidation of succinate to fumarate, producing FADH2. Part of Complex II in ETC.

Fumarase

Hydrates fumarate to malate by adding water across a double bond.

Malate Dehydrogenase

Oxidizes malate to oxaloacetate, producing NADH.

Thioester Bond

A high-energy bond in acetyl-CoA whose hydrolysis drives citrate formation.

Substrate-Level Phosphorylation

Direct formation of ATP or GTP from high-energy intermediates in metabolism.

Nucleoside Diphosphate Kinase (NDK)

Converts GTP to ATP by transferring phosphate groups between nucleotides.

Fats burn in the flames of carbohydrates

A phrase describing how acetyl-CoA from fats needs oxaloacetate from carbohydrates to enter the CAC.

Regulation by ADP

ADP activates enzymes in the CAC, indicating a need for ATP synthesis.

Regulation by ATP and NADH

ATP and NADH inhibit CAC enzymes, signaling high energy status.

Calcium Activation

Ca²+ activates isocitrate and alpha-KG dehydrogenases, enhancing CAC during muscle activity.

Acetyl-CoA Regulation

Activates pyruvate carboxylase, inhibits PDC; ensures CAC has oxaloacetate when fatty acids provide acetyl-CoA.

Mixed Anhydride

A high-energy bond formed between a carboxylic acid and a phosphate; involved in substrate-level phosphorylation.

Methylene Group

A CH2 group; converted to a carbonyl in final CAC steps (succinate to OAA).

Hydrolysis of Thioester

Drives the exergonic condensation of Acetyl-CoA with OAA to form citrate.

C4 Intermediate

Four-carbon molecules like OAA and succinate involved in the CAC.

C6 Compound

Citrate, formed from OAA (C4) and Acetyl-CoA (C2).

C5 Compound

alpha-Ketoglutarate; formed after first oxidative decarboxylation.

Energy Investment Phase

Term not explicitly in CAC but often contrasted in glycolysis; CAC skips this phase.

NAD+/NADH Coenzyme Pair

Key electron carriers; NAD+ is reduced in CAC and feeds electrons into the ETC.

FAD/FADH2 Coenzyme Pair

FAD is a prosthetic group reduced during succinate oxidation.

Citrate

First intermediate in CAC; a C6 molecule synthesized by citrate synthase.

Isocitrate

Formed from citrate via isomerization by aconitase; a secondary alcohol.

alpha-Ketoglutarate

5-carbon intermediate; undergoes oxidative decarboxylation to succinyl-CoA.

Succinyl-CoA

High-energy thioester intermediate; converted to succinate with GTP formation.

Succinate

C4 intermediate formed after substrate-level phosphorylation.

Fumarate

Formed via oxidation of succinate by succinate dehydrogenase.

Malate

Hydrated product of fumarate; oxidized to regenerate OAA.

Oxaloacetate (OAA)

The CAC starting and ending molecule; a C4 compound that condenses with acetyl-CoA.

Pyruvate Carboxylase

Anaplerotic enzyme converting pyruvate to OAA; activated by acetyl-CoA.

Prosthetic Group

A non-dissociable coenzyme, e.g., FAD in succinate dehydrogenase.

Electron Transport Chain (ETC)

Series of complexes transferring electrons from NADH/FADH2 to oxygen.

Complex I

ETC complex accepting electrons from NADH.

Complex II

ETC complex that includes succinate dehydrogenase and accepts electrons from FADH2.

Ubiquinone (Q)

Mobile electron carrier that shuttles electrons from Complex I/II to Complex III.

Oxidation

Loss of electrons; key feature in multiple CAC steps producing NADH or FADH2.

Reduction

Gain of electrons; occurs when NAD+ or FAD are reduced.

Substrate-Level Phosphorylation (SLP)

Direct ATP or GTP formation via intermediate transfer of phosphate.

ATP Synthase

Enzyme that synthesizes ATP using the proton gradient across the inner mitochondrial membrane.

Proton Gradient

Electrochemical gradient across IMM; drives ATP synthesis.

Uncoupling

Dissipating the proton gradient without ATP synthesis; increases O2 consumption and heat.

2,4-DNP

Chemical uncoupler that increases metabolic rate and heat by collapsing the proton gradient.

Product Inhibition

Enzyme inhibition by its product, e.g., citrate inhibits citrate synthase.

Feedback Inhibition

Pathway regulation where end products inhibit upstream enzymes.

Allosteric Regulation

Regulation via binding of effectors to non-active sites on enzymes.

ADP

Allosteric activator of CAC enzymes and substrate for ATP synthase.

ATP

Allosteric inhibitor; high levels downregulate the CAC.

Ca2+

Allosterically activates isocitrate and alpha-KG dehydrogenases during muscle contraction.

Pyruvate Dehydrogenase Complex (PDC)

Converts pyruvate to acetyl-CoA; regulated by phosphorylation and allosteric mechanisms.