Glycolysis Regulation: Key Enzymes

Net glycolysis (cytoplasm):

Glucose + 2 Pᵢ + 2 ADP + 2 NAD⁺ → 2 pyruvate + 2 ATP + 2 NADH + 2 H⁺ + 2 H₂O

Equation not balanced chemically, and exact balanced equation depends on ionization state of reactants and products.

Glycolysis Regulation: ATP Requiring Steps

REQUIRE ATP

Glucose → Glucose-6-P

• Hexokinase/glucokinase (inhibited by Glucose-6-P)

Fructose-6-P → Fructose-1,6-BP

• Phosphofructokinase-1 (rate-limiting step)
• Inhibited by AMP, Fructose-2,6-bisphosphate, ATP, citrate

Glycolysis Regulation: ATP Producing Steps

PRODUCE ATP

1,3-BPG → 3-PG

• Phosphoglycerate kinase

Phosphoenolpyruvate → Pyruvate

• Pyruvate kinase
• Inhibited by Fructose-1,6-bisphosphate, ATP, alanine, glucagon

Regulation by Fructose-2,6-bisphosphate

Fructose bisphosphatase-2 (FBPase-2) and phosphofructokinase-2 (PFK-2) are the same bifunctional enzyme whose function is reversed by phosphorylation by protein kinase A.

#boundingbox

Fructose-2,6-bisphosphate Regulation: Fasting vs. Fed

Fasting state: ↑ glucagon → ↑ cAMP → ↑ protein kinase A → ↑ FBPase-2, ↓ PFK-2, less glycolysis, more gluconeogenesis.

Fed state: ↑ insulin → ↓ cAMP → ↓ protein kinase A → ↓ FBPase-2, ↑ PFK-2, more glycolysis, less gluconeogenesis.

FaBian the Peasant (FBP) has to work hard when starving.

Prince FredericK (PFK) works only when fed.

Pyruvate Dehydrogenase Complex

Mitochondrial enzyme complex linking glycolysis and TCA cycle. Differentially regulated in fed (active)/fasting (inactive) states.

Reaction: pyruvate + NAD⁺ + CoA → acetyl-CoA + CO₂ + NADH

Contains 3 enzymes requiring 5 cofactors:

1. Thiamine pyrophosphate (B₁)
2. Lipoic acid
3. CoA (B₅, pantothenic acid)
4. FAD (B₂, riboflavin)
5. NAD⁺ (B₃, niacin)

Activated by: ↑ NAD⁺/NADH ratio, ↑ ADP, ↑ Ca²⁺

Pyruvate Dehydrogenase Complex: Comparisons and Clinical Notes

The complex is similar to the α-ketoglutarate dehydrogenase complex (same cofactors, similar substrate and action), which converts α-ketoglutarate → succinyl-CoA (TCA cycle).

The lovely coenzymes for nerds.

Arsenic inhibits lipoic acid. Arsenic poisoning clinical findings: imagine a vampire (pigmentary skin changes, skin cancer), vomiting and having diarrhea, running away from a cutie (QT prolongation) with garlic breath.

Topics Covered:

• Glycolysis Net Reaction
• Glycolysis: ATP Investment Phase
• Glycolysis: ATP Payoff Phase
• Fructose-2,6-BP Bifunctional Enzyme
• Fructose-2,6-BP: Fasting and Fed States
• Pyruvate Dehydrogenase Complex
• PDC: α-Ketoglutarate & Arsenic