BB ch 16, p2

Citric Acid Cycle

An eight-step mitochondrial pathway that oxidizes acetyl-CoA to CO₂, producing NADH, FADH₂, and GTP.

Krebs Cycle

Alternative name for the citric acid (TCA) cycle discovered by Hans Krebs.

Tricarboxylic Acid (TCA) Cycle

Another name for the citric acid cycle, emphasizing the three carboxylate groups of its intermediates.

Amphibolic Pathway

A metabolic pathway that functions in both catabolism and anabolism, like the TCA cycle.

Pyruvate Dehydrogenase Complex (PDC)

A multienzyme complex that converts pyruvate to acetyl-CoA, CO₂, and NADH.

Pyruvate Dehydrogenase (E1)

The TPP-dependent enzyme of PDC that decarboxylates pyruvate.

Dihydrolipoyl Transacetylase (E2)

The lipoate-containing PDC subunit that transfers the acetyl group to CoA.

Dihydrolipoyl Dehydrogenase (E3)

The FAD-dependent PDC subunit that re-oxidizes reduced lipoamide and yields NADH.

Thiamine Pyrophosphate (TPP)

A PDC coenzyme that stabilizes carbanion intermediates during decarboxylation.

Lipoic Acid

A swinging-arm cofactor that carries acyl groups and electrons within PDC.

Coenzyme A (CoA-SH)

A pantothenate-derived carrier of activated acyl groups such as acetyl-CoA.

Flavin Adenine Dinucleotide (FAD)

A redox cofactor bound to E3 that accepts electrons from reduced lipoamide.

Nicotinamide Adenine Dinucleotide (NAD⁺)

An electron acceptor that receives hydride from FADH₂ in PDC and many TCA reactions.

Decarboxylation of Pyruvate

First PDC step that releases CO₂ and forms hydroxyethyl-TPP.

Acetyl-CoA

A central two-carbon metabolite produced by PDC and entering the TCA cycle.

Biological Tether

A flexible arm (e.g., lipoate or biotin) that swings intermediates between active sites.

Lipoate Arm

The disulfide-containing chain linking lipoic acid to a lysine in E2.

Biotin

A CO₂-carrying vitamin tethered to enzymes like pyruvate carboxylase.

β-Mercaptoethylamine

The reactive sulfhydryl-containing portion of CoA’s pantothenate arm.

Pantothenate

Vitamin B₅ component of CoA and acyl carrier protein.

Citrate Synthase

TCA enzyme that condenses acetyl-CoA with oxaloacetate to form citrate.

Aconitase

Iron–sulfur enzyme that isomerizes citrate to isocitrate via cis-aconitate.

Isocitrate Dehydrogenase

Enzyme that oxidatively decarboxylates isocitrate to α-ketoglutarate, yielding NADH.

α-Ketoglutarate Dehydrogenase Complex

PDC-like complex that converts α-ketoglutarate to succinyl-CoA and CO₂.

Succinyl-CoA Synthetase

TCA enzyme that produces succinate and GTP (or ATP) from succinyl-CoA.

Succinate Dehydrogenase

Inner-membrane enzyme that oxidizes succinate to fumarate and forms FADH₂.

Fumarase

Hydratase that adds water to fumarate to form malate.

Malate Dehydrogenase

Enzyme that oxidizes malate to oxaloacetate, generating NADH.

Oxaloacetate

Four-carbon TCA intermediate that condenses with acetyl-CoA and is regenerated at cycle end.

Citrate

Six-carbon product of acetyl-CoA and oxaloacetate condensation.

Isocitrate

Six-carbon isomer of citrate formed by aconitase.

α-Ketoglutarate

Five-carbon TCA intermediate produced from isocitrate.

Succinyl-CoA

Four-carbon, CoA-activated intermediate formed by α-ketoglutarate dehydrogenase.

Succinate

Four-carbon dicarboxylate produced from succinyl-CoA and precursor to fumarate.

Fumarate

Trans-alkene formed by oxidation of succinate; hydrated to malate.

Malate

Hydroxy dicarboxylate formed from fumarate, oxidized to oxaloacetate.

Substrate-Level Phosphorylation

ATP or GTP generation directly from a high-energy intermediate like succinyl-CoA.

Dehydrogenation

Removal of hydrogen to create a double bond, producing NADH or FADH₂.

Hydration

Addition of water across a double bond, as in fumarase reaction.

Oxidative Decarboxylation

Simultaneous oxidation and CO₂ release, e.g., isocitrate dehydrogenase step.

Anaplerotic Reaction

“Filling-up” reaction that replenishes TCA intermediates withdrawn for biosynthesis.

Pyruvate Carboxylase

Biotin enzyme that converts pyruvate and HCO₃⁻ to oxaloacetate using ATP.

PEP Carboxykinase

Enzyme that carboxylates phosphoenolpyruvate to oxaloacetate using GTP.

PEP Carboxylase

Plant and bacterial enzyme that fixes CO₂ to PEP, yielding oxaloacetate and Pi.

Malic Enzyme

Enzyme that reduces CO₂ and pyruvate to malate while oxidizing NAD(P)H.

Regulation of TCA Cycle

Control primarily at citrate synthase, isocitrate dehydrogenase, and α-KGDH steps.

Allosteric Inhibition

Down-regulation of enzyme activity by binding of effectors like ATP or NADH.

Allosteric Activation

Enhancement of enzyme activity by effectors such as ADP or Ca²⁺.

NADH Inhibition

Feedback suppression of TCA enzymes when reduced NADH accumulates.

ATP Inhibition

High cellular energy charge that slows TCA flux via several enzymes.

ADP Activation

Signal of low energy that stimulates isocitrate dehydrogenase and citrate synthase.

Calcium Activation

Increase in Ca²⁺ during muscle activity that stimulates PDH, isocitrate DH, and α-KGDH.

Amphibolic Significance

The TCA cycle’s dual role in energy production and biosynthetic precursor supply.

Biosynthetic Precursors

Metabolites like α-ketoglutarate, succinyl-CoA, and oxaloacetate used for anabolism.

Glutamate Synthesis

Transamination of α-ketoglutarate to form glutamate, precursor for several amino acids.

Porphyrin Synthesis

Use of succinyl-CoA to initiate heme and chlorophyll biosynthesis.

Pyrimidine Nucleotide Synthesis

Utilization of fumarate or oxaloacetate carbon skeletons to build pyrimidines.

Purine Nucleotide Synthesis

Dependence on glutamine (from α-ketoglutarate) for purine ring nitrogen.

Glyoxylate Cycle

Modified pathway enabling net carbohydrate synthesis from acetate by bypassing CO₂-producing steps.

Isocitrate Lyase

Glyoxylate cycle enzyme that splits isocitrate into succinate and glyoxylate.

Malate Synthase

Enzyme that condenses glyoxylate with acetyl-CoA to form malate.

Glyoxysome

Plant peroxisome-like organelle hosting the glyoxylate cycle.

Acetate-Based Growth

Ability of organisms to use acetate as sole carbon source by means of the glyoxylate cycle.

Short-Circuiting Enzyme

Term for isocitrate lyase and malate synthase, which bypass TCA decarboxylations.

Net Carbohydrate Synthesis from Acetate

Outcome of the glyoxylate shunt, impossible via the full TCA cycle.

Seed Germination

Stage where plants convert stored fatty acids to sugars using the glyoxylate cycle.

Succinate Dehydrogenase Absence

Lack of this enzyme in glyoxysomes, requiring mitochondrial borrowing.

Fumarase Borrowing

Transfer of mitochondrial fumarase function to glyoxylate cycle metabolism.

Malate Dehydrogenase Borrowing

Use of mitochondrial malate dehydrogenase to convert succinate-derived malate to oxaloacetate.

Compartmental Integration

Exchange of intermediates between mitochondria and glyoxysomes during metabolism.

Coordinated Regulation

Control that directs isocitrate either through TCA for energy or glyoxylate for biosynthesis.

Isocitrate Dehydrogenase Phosphorylation

Inactivation of mitochondrial IDH that diverts isocitrate to the glyoxylate cycle.

Glyoxylate vs Citric Acid Partitioning

Decision point controlled by IDH phosphorylation state.

Protein Kinase (Isocitrate Dehydrogenase)

Enzyme that phosphorylates and inhibits IDH when biosynthesis is prioritized.

Protein Phosphatase (Isocitrate Dehydrogenase)

Enzyme that dephosphorylates and activates IDH for energy production.

Pyruvate Dehydrogenase Kinase

Regulatory enzyme that phosphorylates and inactivates the PDH complex.

Pyruvate Dehydrogenase Phosphatase

Enzyme that removes phosphate from PDH, reactivating the complex.

High NADH/NAD⁺ Ratio

Signal of abundant reducing power that inhibits PDH and slows TCA entry.

High Acetyl-CoA/CoA Ratio

Indicator of abundant acetyl units that suppresses PDH activity.

Metabolic Flow Control

Regulation of substrate movement through PDH and the TCA cycle.

Oxidation of Succinate to Oxaloacetate

A trio of dehydrogenation, hydration, and dehydrogenation steps (6–8 of TCA).

Recurring Reaction Theme

Sequence of oxidation, hydration, oxidation seen in TCA and fatty acid metabolism.

Fatty Acid β-Oxidation Connection

Pathway that repeats the succinate–oxaloacetate reaction motif.

Amino Acid Catabolism Connection

Breakdown pathways that mimic TCA’s oxidation–hydration–oxidation pattern.

Aerobic Bacteria

Organisms that run the full TCA cycle for energy when oxygen is available.

Anaerobic Bacteria

Species that use incomplete TCA cycles lacking α-ketoglutarate dehydrogenase.

α-Ketoglutarate Dehydrogenase Deficiency

Absence of this enzyme in anaerobes, causing a biosynthetically oriented TCA branch.

Biosynthetic Products

Amino acids, nucleotides, and heme derived from TCA intermediates.

Cellular Respiration Stage 1

Generation of acetyl-CoA from carbohydrates, fats, and proteins.

Cellular Respiration Stage 2

Oxidation of acetyl-CoA in the TCA cycle to produce NADH/FADH₂.

Cellular Respiration Stage 3

Oxidative phosphorylation using electron transport to make ATP.

Acetate

Two-carbon molecule that feeds the glyoxylate cycle via acetyl-CoA.

Glyoxylate

Two-carbon aldehyde–acid produced by isocitrate lyase.

CO₂-Evolving Steps

Decarboxylations in the TCA cycle that are bypassed in the glyoxylate shunt.

Condensation Reaction

Combination of acetyl-CoA and oxaloacetate catalyzed by citrate synthase.

Dehydration Reaction

Removal of water, as aconitase converts citrate to cis-aconitate.

Hydration Reaction

Addition of water back, turning cis-aconitate into isocitrate.

Reaction 2a

Aconitase-catalyzed dehydration of citrate to cis-aconitate.

Reaction 2b

Aconitase-catalyzed hydration of cis-aconitate to isocitrate.

Reaction 5

Succinyl-CoA synthetase step that yields GTP/ATP and succinate.