Glycolysis and Metabolic Regulation

A complete set of vocabulary flashcards covering the phases, enzymatic steps, regulation, and clinical relevance of the glycolysis pathway based on lecture notes.

Embden-Meyerhof-Parnas Pathway

An alternative name for the Glycolysis pathway, which is an ancient process present in virtually all organisms for glucose catabolism.

Cytoplasm (Cytosol)

The specific cellular location where the glycolysis pathway occurs.

Energy Investment Phase

Phase 1 of glycolysis (Steps 1-5) which involves the expenditure of $2$ ATP to prepare glucose for cleavage into two 3-carbon units.

Energy Payoff Phase

Phase 2 of glycolysis (Steps 6-10) which generates a net gain of $2$ ATP and $2$ NADH while converting glyceraldehyde-3-phosphate into pyruvate.

Hexokinase

An enzyme that catalyzes the irreversible phosphorylation of glucose to glucose-6-phosphate, trapping it in the cell with a $K_m$ for glucose of approximately $0.1\,mM$.

Glucokinase (Hexokinase IV)

A liver and pancreatic isoform of hexokinase with a high $K_m$ ($10\,mM$) that acts as a glucose sensor and is not inhibited by glucose-6-phosphate.

Glucokinase Regulatory Protein (GKRP)

A protein that regulates Glucokinase (Hexokinase IV) in the liver and pancreatic beta-cells.

Phosphoglucose Isomerase

The enzyme in Step 2 that converts glucose-6-phosphate (an aldose) to fructose-6-phosphate (a ketose) in a reversible reaction.

Phosphofructokinase-1 (PFK-1)

The major control point and rate-limiting enzyme of glycolysis that converts fructose-6-phosphate to fructose-1,6-bisphosphate using ATP.

Committed Step

A term describing the PFK-1 reaction because its product, fructose-1,6-bisphosphate, has no other metabolic fate except to complete glycolysis.

Fructose-2,6-Bisphosphate (F-2,6-BP)

The most potent allosteric activator of PFK-1 that shifts its kinetics from a sigmoidal curve to a hyperbolic curve.

PFK-2/FBPase-2

A bifunctional enzyme that regulates the levels of fructose-2,6-bisphosphate; its phosphorylation state is controlled by the insulin/glucagon ratio.

Aldolase

The enzyme in Step 4 that cleaves fructose-1,6-bisphosphate into two triose phosphates: dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P).

Triose Phosphate Isomerase

A 'kinetically perfect' enzyme that interconverts DHAP and G3P, effectively doubling the yield of the energy payoff phase.

Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH)

The enzyme in Step 6 that catalyzes the oxidation and phosphorylation of G3P to 1,3-bisphosphoglycerate, producing NADH.

Arsenate

A molecule that can substitute for phosphate in the GAPDH reaction, forming an unstable intermediate that bypasses ATP generation.

Substrate-level Phosphorylation

The direct transfer of a phosphate group from a high-energy substrate to ADP to form ATP, occurring independently of oxygen and the electron transport chain.

Phosphoglycerate Kinase

The enzyme in Step 7 that generates the first $2$ ATP of the payoff phase by converting 1,3-bisphosphoglycerate to 3-phosphoglycerate.

2,3-Bisphosphoglycerate (2,3-BPG)

An intermediate produced in erythrocytes via a detour from the 1,3-BPG step, used to regulate hemoglobin oxygen affinity.

Phosphoglycerate Mutase

The enzyme in Step 8 that catalyzes the migration of the phosphate group from C-3 to C-2 of phosphoglycerate through a phospho-histidine intermediate.

Enolase

The enzyme in Step 9 that performs a dehydration reaction on 2-phosphoglycerate to form phosphoenolpyruvate (PEP).

Phosphoenolpyruvate (PEP)

A high-energy intermediate in Step 9 with a very high phosphoryl transfer potential used to drive the second substrate-level phosphorylation.

Pyruvate Kinase

The final enzyme in glycolysis (Step 10) that converts PEP to pyruvate and generates the second ATP payoff; it is inhibited by ATP and Acetyl-CoA.

Feedforward Activation

A regulatory mechanism where fructose-1,6-bisphosphate activates pyruvate kinase to ensure the pathway's flow.

Lactate Dehydrogenase

The enzyme that reduces pyruvate to lactate under anaerobic conditions to regenerate $NAD^{+}$ for continued glycolysis.

Warburg Effect

The observation that cancer cells preferentially use glycolysis even when oxygen is abundant (aerobic glycolysis) to provide biosynthetic precursors and rapid ATP.

FDG-PET imaging

A clinical application of the Warburg effect using a radioactive glucose analog ($^{18}F\,FDG$) to visualize high glucose uptake in tumors.

Aldolase B

A liver-specific class I aldolase that produces glyceraldehyde instead of glyceraldehyde-3-phosphate during fructose metabolism.