CHEM 430H Glycolysis/Gluconeogenesis/Glycogen Synth Enzymes

Enzyme matched to reaction catalyzed, function (e.g., phosphorylation), equilibrium status (far or near), and cofactors. All steps but the Fars are reversible for gluconeogenesis, to prevent repeats.

hexokinase

Reaction Catalyzed: Glycolysis Step 1, Glucose to Glucose-6-phosphate

Function: Phosphorlyzes glucose @ C6 to prevent it from leaving cell

Equil Status: Far

Cofactors: ATP

phosphoglucoisomerase

Reaction Catalyzed: Glycolysis Step 2, glucose-6-phosphate to fructose-6-phosphate 

Function: Isomerizes glucose-6-P to create the aldose fructose-6-P, leaving a hydroxyl group open for phosphorylation

Equil Status: Near

Cofactors: None

phosphofructokinase

Reaction Catalyzed: Glycolysis Step 3, fructose-6-phosphate to fructose-1,6-biphosphate

Function: Phosphorylzes fructose-6-phosphate to ensure it goes through glycolysis instead of converting back to glucose.  COMMITTED STEP!

Equil Status: Far

Cofactors: ATP, Mg2+

aldolase

Reaction Catalyzed: Glycolysis Step 4, fructose-1,6-biphosphate to glyceraldehyde-3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP)

Function: Hydrolyzes the fructose ring in the substrate to create 2 phosphorylated products, allowing for net ATP gain later in payoff stage.

Equil Status: Near

Cofactors: None

triose phosphate isomerase

Reaction Catalyzed: Glycolysis Step 5, DHAP to GAP

Function: Isomerizes DHAP to GAP via an enediol intermediate, ensuring that all product from the previous step converts to GAP (the substrate for Step 6).

Equil Status: Near

Cofactors: None

glyceraldehyde-3-phosphate dehydrogenase (GAPDH)

Reaction Catalyzed: Glycolysis Step 6, GAP to 1,3-biphosphoglycerate (1,3-BPG)

Function: Phosphorylates GAP via an oxidation reaction to prevent it from leaving the cell and provide a phosphate group for ATP production

Equil Status: Near

Cofactors: NAD+, Pi for phosphorylation

phosphoglycerate kinase

Reaction Catalyzed: Glycolysis Step 7, 1,3-biphosphoglycerate (1,3-BPG) to 3-phosphoglycerate

Function: Phosphorylzes ADP via 1,3-BPG, producing 2 ATP (substrate-level phosphorylation)

Equil Status: Near

Cofactors: ADP, Mg2+

phosphoglycerate mutase

Reaction Catalyzed: Glycolysis Step 8, 3-phosphoglycerate to 2-phosphoglycerate

Function: Removes phosphate from C3 and places a DIFFERENT phosphate on C3

Equil Status: Near

Cofactors: None

enolase

Reaction Catalyzed: Glycolysis Step 9, 2-phosphoglycerate to phosphoenolpyruvate

Function: Dehydrates 2-phosphoglycerate to produce phosphoenolpyruvate

Equil Status: Near

Cofactors: Mg2+, H2O prod

pyruvate kinase

Reaction Catalyzed: Glycolysis Step 10, phosphoenolpyruvate to pyruvate

Function: Phosphorylzes ADP to ATP using phosphate from phosphoenolpyruvate

Equil Status: Far

Cofactors: Mg2+, K+

lactate dehydrogenase

Reaction Catalyzed: Lactate fermentation, pyruvate to L-lactate

Function: hydrogenates (H2) pyruvate to create L-lactate in absence of O2

Equil Status: 

Cofactors: NADH + H+

pyruvate decarboxylase

Reaction Catalyzed: Alcohol fermentation Step 1, pyruvate to acetaldehyde

Function: Decarboxylates pyruvate to form acetaldehyde, a precursor for ethanol

Equil Status:

Cofactors: H+ and releases CO2

alcohol dehydrogenase

Reaction Catalyzed: Alcohol fermentation Step 2, acetaldehyde to ethanol

Function: hydrogenates (H2) acetaldehyde to form ethanol in absence of O2

Equil Status:

Cofactors: NADH

pyruvate carboxylase

Reaction Catalyzed: Gluconeogenesis Step 1a, pyruvate to oxaloacetate

Function: carboxylates pyruvate to form oxaloacetate intermediate using ATP energy

Equil Status: Near

Cofactors: HCO3-, ATP, Biotin

phosphoenolpyruvate carboxykinase

Reaction Catalyzed: Gluconeogenesis Step 1b, oxaloacetate to phosphoenolpyruvate

Function: decarboxylates oxaloacetate and applies energy to add phosphate from GTP to form phosphoenolpyruvate

Equil Status: Far

Cofactors: GTP, produces GDP + CO2

fructose 1,6-bisphosphatase-1

Reaction Catalyzed: Gluconeogenesis Step 8, fructose 1,6-bisphosphate to fructose 6-phosphate

Function: Dephosphorylates fructose 1,6-bisphosphate to form fructose 6-phosphate, allowing it to “escape” glycolysis and get on track to glucose.

Equil Status: Far

Cofactors: H2O, produces Pi

glucose 6-phosphatase

Reaction Catalyzed: Gluconeogenesis Step 10, glucose 6-phosphate to glucose

Function: Like Step 8, dephosphorylates glucose 6-phosphate to form glucose.

Equil Status: Far…

Cofactors: H2O, produces Pi

phosphoglucomutase

Reaction Catalyzed: Glycogen Synthesis Step 1, Glucose-6-phosphate to Glucose-1-Phosphate

Function: Dephosphorylates glucose-6-P @ C6 and phosphorylates it @ C1

Equil Status: Near

Cofactors: None

UDP-glucose pyrophosphorylase

Reaction Catalyzed: Glycogen Synthesis Step 2, glucose-1-phosphate to UDP-glucose

Function: Attaches glucose-1-phosphaste to UTP by removing 2 phosphate groups (pyrophosphate) and linking the last phosphate from UTP to glucose-1-P, resulting in UDP-glucose

Equil Status: Near

Cofactors: UTP, produces PPi

glycogen synthase

Reaction Catalyzed: Glycogen Synthesis Step 3, UDP-glucose to glycogen chain

Function: Links the glucose component of UDP-glucose to the nonreducing end of an existing glucose chain (glycogen), resulting in free UDP

Equil Status: Near

Cofactors: None

nucleoside diphosphate kinase

Reaction Catalyzed: Glycogen Synthesis Side-Step, UDP to UTP

Function: Phosphorylates UDP to produce UTP via ATP

Equil Status: Far

Cofactors: ATP

pyrophosphatase

Reaction Catalyzed: Glycogen Synthesis Side-Step, PPi to 2 Pi

Function: Hydrolyzes PPi to produce 2 Pi for re-use in other pathways

Equil Status: Near

Cofactors: H2O for hydrolysis

glycogen debranching enzyme

Reaction Catalyzed: Transfer of a(1→4) chain to a(1→6) linkage and hydrolysis of last remaining glucose in chain

Function: Prepares glycogen chains for glycogen phosphorylase, which cleaves 3 glucose units and allows GDE to repeat

Equil Status: Far probably

Cofactors: H2O

glycogen phosphorylase

Reaction Catalyzed: Cleavage of 3 glucose units from glycogen chain

Function: Takes glucose from glycogen storage

Equil Status: Neer

Cofactors: none