Glycolysis, Gluconeogenesis & TCA Cycle – Vocabulary Review

A set of 90 vocabulary flashcards covering enzymes, reactions, cofactors, regulation, and key concepts in glycolysis, gluconeogenesis, and the citric acid cycle.

Glycolysis

Metabolic pathway that converts glucose into pyruvate while producing ATP and NADH.

Preparatory Phase (of glycolysis)

First five reactions of glycolysis that consume ATP to phosphorylate and split glucose.

Pay-off Phase (of glycolysis)

Last five glycolytic steps that generate ATP and NADH from glyceraldehyde-3-phosphate.

Hexokinase

Enzyme that irreversibly phosphorylates glucose to glucose-6-phosphate using ATP.

Phosphohexose Isomerase

Reversible enzyme that converts glucose-6-phosphate to fructose-6-phosphate.

Phosphofructokinase-1 (PFK-1)

Key regulatory enzyme that irreversibly converts fructose-6-phosphate to fructose-1,6-bisphosphate.

Aldolase

Enzyme that cleaves fructose-1,6-bisphosphate into glyceraldehyde-3-phosphate and dihydroxyacetone phosphate.

Triose Phosphate Isomerase

Catalyzes reversible interconversion of dihydroxyacetone phosphate and glyceraldehyde-3-phosphate.

Glyceraldehyde-3-phosphate Dehydrogenase

Catalyzes oxidation and phosphorylation of GAP to 1,3-bisphosphoglycerate, producing NADH.

Phosphoglycerate Kinase

Performs substrate-level phosphorylation of ADP while converting 1,3-bisphosphoglycerate to 3-phosphoglycerate.

Phosphoglycerate Mutase

Moves the phosphate from C-3 to C-2, forming 2-phosphoglycerate.

Enolase

Dehydrates 2-phosphoglycerate to phosphoenolpyruvate (PEP).

Pyruvate Kinase

Irreversibly transfers phosphate from PEP to ADP, yielding ATP and pyruvate.

Irreversible Step (in glycolysis)

Reaction with large negative ΔG that drives pathway forward; catalyzed by hexokinase, PFK-1, and pyruvate kinase.

Substrate-level Phosphorylation

Direct synthesis of ATP or GTP by transfer of a phosphate group from a high-energy intermediate.

PEP Tautomerization

Conversion of enol-pyruvate to keto-pyruvate after phosphate loss, making PEP a high-energy donor.

Overall Glycolysis Equation

Glucose + 2 ADP + 2 Pi + 2 NAD⁺ → 2 Pyruvate + 2 ATP + 2 NADH + 2 H⁺.

Role of NAD⁺ in Glycolysis

Electron acceptor required for the GAPDH step; must be regenerated for glycolysis to continue.

NADH Reoxidation

Process of converting NADH back to NAD⁺ via respiration or fermentation.

Glycogen Phosphorylase

Enzyme that releases glucose-1-phosphate from glycogen for entry into glycolysis.

Lactose

Disaccharide hydrolyzed to glucose and galactose before glycolysis.

Sucrose

Disaccharide split into glucose and fructose that feed into glycolysis.

Fructose Entry Point

Enters glycolysis as dihydroxyacetone phosphate or glyceraldehyde-3-phosphate, depending on tissue.

Galactose Entry Point

Converted to glucose-1-phosphate then to glucose-6-phosphate before glycolysis.

Mannose Entry Point

Isomerized to fructose-6-phosphate for glycolysis.

Pyruvate Fate

Can become acetyl-CoA, lactate, or ethanol + CO₂ depending on conditions.

Fermentation

Anaerobic pathway that regenerates NAD⁺ while producing lactate or ethanol.

Lactic Acid Fermentation

Reduction of pyruvate to lactate in muscle; lactate can be transported to liver for glucose synthesis.

Cori Cycle

Cycle in which lactate from muscle is converted to glucose in the liver.

Ethanol Fermentation

Yeast pathway converting pyruvate to ethanol and CO₂, regenerating NAD⁺.

Pyruvate Decarboxylase

TPP- and Mg²⁺-dependent enzyme that converts pyruvate to acetaldehyde and CO₂.

Alcohol Dehydrogenase

Zn²⁺-dependent enzyme that reduces acetaldehyde to ethanol using NADH.

Thiamine Pyrophosphate (TPP)

Cofactor that stabilizes carbanion intermediates in decarboxylation reactions.

Mg²⁺ (in pyruvate decarboxylase)

Metal ion that assists TPP binding and catalysis in ethanol fermentation.

Zn²⁺ (in alcohol dehydrogenase)

Metal ion that polarizes the carbonyl of acetaldehyde for reduction.

Glycolysis Location

Occurs predominantly in muscle and brain cytosol.

Gluconeogenesis Location

Takes place mainly in liver (and kidney) cytosol and mitochondria.

Reversible Reaction (shared)

Step used by both glycolysis and gluconeogenesis because its ΔG is near zero.

Futile Cycle

Simultaneous operation of opposing pathways that would waste energy; prevented by regulation.

Pyruvate Carboxylase

Biotin-dependent mitochondrial enzyme converting pyruvate to oxaloacetate using ATP.

Biotin

Vitamin cofactor that transiently carries activated CO₂ in carboxylation reactions.

Oxaloacetate (OAA)

Four-carbon TCA intermediate and gluconeogenic precursor formed from pyruvate.

Phosphoenolpyruvate Carboxykinase (PEPCK)

Enzyme that converts OAA to PEP using GTP and releasing CO₂.

Gluconeogenesis Energy Cost

Formation of one glucose requires 4 ATP, 2 GTP, and 2 NADH.

Tethering (in biotin enzymes)

Attachment of biotin on a flexible lysine arm that moves CO₂ between active sites.

Glucose Precursors in Animals

Sugars (pyruvate, lactate, OAA) and amino acids can be converted to glucose.

Fatty Acids & Glucose

Even-chain fatty acids cannot supply net carbon for glucose synthesis in animals.

Acetyl-CoA

Two-carbon unit produced from pyruvate or fatty acids; enters TCA cycle.

Citrate Synthase

Irreversible enzyme that condenses acetyl-CoA with OAA to form citrate.

Aconitase

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

Iron–Sulfur Center (in aconitase)

Cluster that facilitates dehydration and rehydration steps during citrate isomerization.

Isocitrate Dehydrogenase

Catalyzes oxidative decarboxylation of isocitrate to α-ketoglutarate, forming NADH and CO₂.

α-Ketoglutarate Dehydrogenase

Complex that converts α-ketoglutarate to succinyl-CoA, producing NADH and CO₂.

Succinyl-CoA Synthetase

Generates GTP while converting succinyl-CoA to succinate.

Succinate Dehydrogenase

Membrane-bound enzyme oxidizing succinate to fumarate, producing FADH₂.

Fumarase

Hydrates fumarate to malate in the TCA cycle.

Malate Dehydrogenase

Oxidizes malate to oxaloacetate, generating NADH.

TCA Cycle Output (per turn)

3 NADH, 1 FADH₂, 1 GTP, 2 CO₂ and regenerated CoA-SH.

Amphibolic Pathway

Pathway serving both degradative (catabolic) and biosynthetic (anabolic) roles; exemplified by TCA cycle.

Anaplerotic Reaction

Reaction that replenishes depleted TCA intermediates, e.g., pyruvate carboxylase forming OAA.

PDH Regulation

Pyruvate dehydrogenase is inactivated by phosphorylation when ATP is high and activated when ATP is low.

ATP Effect on PDH Kinase

High ATP stimulates PDH kinase, promoting PDH phosphorylation and shutdown of acetyl-CoA production.

Citrate as Biosynthetic Precursor

Leaves mitochondria to provide acetyl units for fatty acid and sterol synthesis.

α-Ketoglutarate as Precursor

Provides carbon skeletons for glutamate and other amino acids.

Succinyl-CoA as Precursor

Starting material for porphyrin and heme biosynthesis.

Malate as Precursor

Can be converted to pyruvate or used for gluconeogenesis.

Oxaloacetate as Precursor

Converted to PEP for glucose synthesis or to aspartate for amino acids.

CO₂ Release Order in TCA

Both CO₂ molecules are lost before succinyl-CoA formation and originate from oxaloacetate.

Low Product Concentration (steps 5-8)

Keeping products scarce drives the later TCA reactions forward.

GTP Production (TCA)

Generated by succinyl-CoA synthetase and can convert to ATP via nucleoside diphosphate kinase.

FADH₂ Production (TCA)

Formed when succinate is oxidized to fumarate by succinate dehydrogenase.

NADH Production (TCA)

Produced in steps catalyzed by isocitrate DH, α-ketoglutarate DH, and malate DH.

Substrate Availability Regulation

Many TCA enzymes are controlled by the concentration of their substrates.

Product Inhibition (TCA)

Accumulation of reaction products slows enzyme activity, as seen with citrate synthase and succinyl-CoA synthetase.

Oxidative Decarboxylation

Reaction combining oxidation with loss of CO₂, generating reduced cofactors.

GAPDH Reaction Type

Simultaneous oxidation of aldehyde and phosphorylation forming a high-energy acyl phosphate.

Enolase Dehydration

Removal of water from 2-phosphoglycerate to create the high-energy PEP.

Mutase Reaction

Intramolecular transfer of a functional group, such as phosphate shift by phosphoglycerate mutase.

Aldol Cleavage

Breakdown of a carbon–carbon bond in fructose-1,6-bisphosphate by aldolase.

Glycogen

Branched glucose polymer serving as an energy reserve in animals.

Starch

Plant polysaccharide broken down by amylase to supply glucose.

Tumor Glycolysis Inhibition

Lowering glucose supply can impede glycolysis and growth in cancer cells.

Biotinyl-Lysine Tether

Long flexible arm that swings biotin between catalytic sites in pyruvate carboxylase.

Mg²⁺ as Enzyme Cofactor

Stabilizes negative charges on ATP and intermediates in many metabolic reactions.

Zn²⁺ as Enzyme Cofactor

Acts as a Lewis acid in enzymes like alcohol dehydrogenase.

Role of Thiamine (Vitamin B₁)

Provides TPP for decarboxylation of α-keto acids such as pyruvate.

ATP Yield from Glycolysis

Net production of 2 ATP per glucose via substrate-level phosphorylation.

ATP Consumed in Glycolysis

Two ATP are invested during the preparatory phase (hexokinase and PFK-1 steps).

Substrate-Level Phosphorylation (definition)

Formation of ATP/GTP by direct transfer of a phosphoryl group to ADP/GDP without an electron transport chain.

Anaplerotic Example: Pyruvate Carboxylase

Adds CO₂ to pyruvate to regenerate oxaloacetate, replenishing the TCA cycle.