Glycolysis pt 1

What are the four major pathways of glucose utilization?

Storage (glycogen/starch), Glycolysis, Pentose Phosphate Pathway, and Synthesis of Structural Polysaccharides.

What is the purpose of glycolysis?

To convert glucose into pyruvate while capturing energy as ATP and NADH.

What are the two phases of glycolysis?

The Preparatory Phase (phosphorylation and cleavage of glucose) and the Payoff Phase (oxidative conversion of glyceraldehyde 3-phosphate to pyruvate with ATP and NADH production).

What is the net ATP yield from one glucose molecule in glycolysis?

2 ATP (2 ATP consumed in the preparatory phase, 4 ATP produced in the payoff phase).

How many NADH molecules are produced per glucose in glycolysis?

2 NADH.

What is the final product of glycolysis?

2 pyruvate molecules (plus 2 ATP and 2 NADH per glucose).

What are feeder pathways for glycolysis?

Pathways that convert other sugars (galactose, fructose, mannose) and storage polymers (glycogen, starch) into glycolytic intermediates.

How does glycogen enter glycolysis?

Glycogen phosphorylase cleaves glucose from glycogen, yielding glucose 1-phosphate, which is converted to glucose 6-phosphate by phosphoglucomutase.

How does lactose feed into glycolysis?

Lactase hydrolyzes lactose into glucose and galactose; galactose is converted via UDP-galactose to glucose 1-phosphate, then glucose 6-phosphate.

How does fructose (from diet) enter glycolysis?

Fructokinase converts fructose to fructose 1-phosphate, which is cleaved by fructose 1-phosphate aldolase into glyceraldehyde and DHAP (dihydroxyacetone phosphate).

What is Step 1 of glycolysis and which enzyme catalyzes it?

Phosphorylation of glucose to glucose 6-phosphate by hexokinase (eukaryotes) or glucokinase (prokaryotes), using ATP. ΔG'° = -16.7 kJ/mol.

Why is Step 1 of glycolysis important?

Phosphorylation traps glucose inside the cell and lowers intracellular glucose concentration to allow further uptake.

What cofactor assists hexokinase in Step 1?

Mg²⁺, which shields the negative charges on ATP to facilitate nucleophilic attack by the C6 oxygen of glucose.

How is Step 1 regulated?

Mainly by substrate inhibition — glucose 6-phosphate inhibits hexokinase.

What is Step 2 of glycolysis and which enzyme catalyzes it?

Isomerization of glucose 6-phosphate to fructose 6-phosphate by phosphohexose isomerase. ΔG'° = +1.7 kJ/mol.

Why is the isomerization in Step 2 necessary?

It moves the carbonyl from C1 to C2, which is a prerequisite for the second phosphorylation (Step 3) and the aldol cleavage (Step 4). It also allows C1 to be phosphorylated.

What type of catalysis does phosphohexose isomerase use?

General acid/base catalysis via an active-site glutamate residue, proceeding through a cis-enediol intermediate.

What is Step 3 of glycolysis and which enzyme catalyzes it?

Phosphorylation of fructose 6-phosphate to fructose 1,6-bisphosphate by phosphofructokinase-1 (PFK-1), using ATP. ΔG'° = -14.2 kJ/mol.

Why is Step 3 considered the first committed step of glycolysis?

Because fructose 1,6-bisphosphate is committed to proceed through glycolysis to pyruvate; it cannot be redirected to other pathways.

How is PFK-1 (Step 3) regulated?

It is inhibited by high ATP (signals sufficient energy) and activated by fructose 2,6-bisphosphate and AMP. It is the major regulatory step of glycolysis.

What is Step 4 of glycolysis and which enzyme catalyzes it?

Aldol cleavage of fructose 1,6-bisphosphate into glyceraldehyde 3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP) by aldolase. ΔG'° = +23.8 kJ/mol.

What type of catalysis do Class I aldolases (animals and plants) use?

Covalent catalysis — an active-site lysine forms a Schiff base (imine) intermediate with the substrate carbonyl, facilitating C-C bond cleavage.

What type of catalysis do Class II aldolases (fungi and bacteria) use?

Metal ion catalysis (e.g., Zn²⁺) to stabilize the enolate intermediate during C-C bond cleavage.

What is Step 5 of glycolysis and which enzyme catalyzes it?

Interconversion of DHAP to glyceraldehyde 3-phosphate (GAP) by triose phosphate isomerase. This funnels both 3-carbon products into a single pathway.

What is Step 6 of glycolysis and which enzyme catalyzes it?

Oxidation and phosphorylation of GAP to 1,3-bisphosphoglycerate by glyceraldehyde 3-phosphate dehydrogenase, producing NADH from NAD⁺.

Why is Step 6 a prerequisite for Step 7?

The oxidative phosphorylation in Step 6 creates a high-energy acyl phosphate bond in 1,3-bisphosphoglycerate that drives ATP synthesis in Step 7.

What is Step 7 of glycolysis and which enzyme catalyzes it?

Transfer of the phosphate from 1,3-bisphosphoglycerate to ADP to produce ATP and 3-phosphoglycerate by phosphoglycerate kinase (substrate-level phosphorylation).

What is Step 8 of glycolysis and which enzyme catalyzes it?

Migration of the phosphoryl group from C3 to C2 of 3-phosphoglycerate to form 2-phosphoglycerate by phosphoglycerate mutase.

Why is Step 8 necessary?

Moving the phosphoryl group from C3 to C2 sets up the final dehydration step, which activates the phosphate for transfer to ADP.

What is Step 9 of glycolysis and which enzyme catalyzes it?

Dehydration of 2-phosphoglycerate to phosphoenolpyruvate (PEP) by enolase, releasing water.

Why does dehydration in Step 9 matter?

It creates the high-energy enol phosphate bond in PEP, activating it for phosphate transfer to ADP in the final step.

What is Step 10 of glycolysis and which enzyme catalyzes it?

Transfer of the phosphate from PEP to ADP to form pyruvate and ATP by pyruvate kinase (substrate-level phosphorylation). ΔG'° highly negative; irreversible.

What is substrate-level phosphorylation?

Direct transfer of a phosphate group from a high-energy substrate intermediate to ADP to form ATP, without the involvement of the electron transport chain.

What is the purpose of the Pentose Phosphate Pathway?

To generate NADPH (for detoxification and biosynthesis of lipids and nucleotides) and ribose 5-phosphate (for nucleotide synthesis) via oxidation of glucose.

Why is phosphorylation of glucose intermediates important for keeping them in the cell?

Phosphorylated compounds are charged and cannot cross the lipid bilayer, so they are trapped inside the cell.

Why did glycolysis likely evolve before photosynthesis?

It developed under anaerobic conditions early in evolution, when oxygen was absent, as a way to extract energy from glucose without oxygen.

What is the overall chemical logic of the preparatory phase of glycolysis?

Glucose is phosphorylated twice (using 2 ATP), isomerized, and cleaved into two phosphorylated 3-carbon sugars — priming them to release energy in the payoff phase.

What is the overall chemical logic of the payoff phase of glycolysis?

Each 3-carbon sugar is oxidized, and the energy is captured by synthesizing ATP (4 total) and NADH (2 total), yielding pyruvate as the final product.