Glycolysis, Fermentation and Warburg effect

Kinase

Transfer of phosphoryl group

Mutase

Intramolecular transfer of functional group

Dehydrogenase

Redox reaction involving transfer of electrons

Isomerase

Rearrangement of atoms within molecule

Catabolism

Breakdown to release energy

Anabolism

Synthesis that requires energy

Aerobic

Requires oxygen

Anaerobic

Without oxygen

Oxidation

Loss of electron
LEO
Loss of H or gain of O

Reduction

Gain of electron
GER

Gain of H or loss of O

What happens to Redox cofactors

Opposite of reactant

NAD+/NADH

Catabolic

NADP+/NADPH

Anabolic

Co-substrates

NAD+ and NADP+

Prosthetic groups

FAD and FMN

Glycolysis

Location → Cytosol

Net reaction → Glucose → 2 pyruvate + 2ATP + 2 NADH

Irreversible steps of glycolysis

Hexokinase

PFK-1

Pyruvate kinase

Major regulatory step of glycolysis

PFK-1

Glycolysis

Glucose -(hexokinase/glucokinase + ATP)→

G6P ←(phosphohexose isomerase)→

F6P ←(phosphofructokinase-1 + ATP)→

F1,6-BP ←(aldolase)→

DHAP + G3P ←(triose phosphate isomerase)→

2 G3P ←(G3P dehydrogenase + NAD+)→

2 1,3-BPG ←(phosphoglycerate kinase + ADP)→

2 3-PG ←(phosphoglycerate mutase)→

2 2-PG ←(enolase → H2O)→

2 PEP -(pyruvate kinase + ADP)→

2 pyruvate

Substrate-level phosphorylation

ATP formation by direct transfer of a phosphate from a high-energy intermediate

1,3-BPG & PEP

GLUT4

Insulin-sensitive

Location → muscle and adipose tissue

2,3-BPG

Decreases hemoglobin’s affinity for oxygen

Fermentation

Regeneration of NAD+ from NADH under anaerobic conditions

Pyruvate → alcohol + homolactic

Homolactic fermentation product

Location → Skeletal muscle during exercise, RBC

Glucose + 2ADP + 2Pi ←(alcohol dehydrogenase)→ 2 Lactate + 2 ATP + 2 H2O

Alcoholic fermentation product

Yeast

Glucose + 2ADP + 2Pi + 2H+ ←(lactate dehydrogenase)→ 2 Ethanol + 2CO2 + 2ATP +2H2O

Cori Cycle

Lactate transported to liver → converted to glucose → muscle

Warburg Effect

Cancel cells favor glycolysis even with oxygen

Hexokinase

Muscle

Works when glucose is scarce

Inhibited by G6P

Glucokinase

Liver

Only active with high glucose (after meal)

Kinases protect against ATP hydrolysis

Substrate positioning

Induced fit

Catalytic residues

Mg2+ coordination