GLYCOLYSIS

Major pathways of glucose utilization.

The two phases of glycolysis.

Three possible catabolic fates of the pyruvate formed in glycolysis.

The Preparatory Phase of Glycolysis Requires ATP

Phosphorylation of Glucose

Conversion of Glucose 6-Phosphate to Fructose 6-Phosphate

Phosphorylation of Fructose 6Phosphate to Fructose 1,6-Bisphosphate

Cleavage of Fructose 1,6-Bisphosphate

Interconversion of the Triose Phosphates

The Payoff Phase of Glycolysis Yields ATP and NADH

Oxidation of Glyceraldehyde 3 Phosphate to 1,3 Bisphosphoglycerate

The glyceraldehyde 3 phosphate dehydrogenase reaction

After 1. formation of the enzyme-substrate complex,2. a covalent thiohemiacetal linkage forms between the substrateand the —SH group of a Cys residue—facilitated by acid-basecatalysis with a neighboring base catalyst, probably a His residue.3. This enzyme-substrate intermediate is oxidized by NAD+ boundto the active site, forming a covalent acyl-enzyme intermediate, athioester. 4. The newly formed NADH leaves the active site and isreplaced by another NAD+ molecule. The bond between the acylgroup and the thiol group of the enzyme has a very high standard freeenergy of hydrolysis. 5. This bond undergoes phosphorolysis (attackby Pi), releasing the acyl phosphate product, 1,3-bisphosphoglycerate.Formation of this product conserves much of the free energy liberatedduring oxidation of the aldehyde group of glyceraldehyde 3-phosphate.

Phosphoryl Transfer from 1,3-Bisphosphoglycerate to ADP

Conversion of 3-Phosphoglycerate to 2-Phosphoglycerate

The phosphoglycerate mutase reaction.

Dehydration of 2-Phosphoglycerate to Phosphoenolpyruvate

Transfer of the Phosphoryl Group from Phosphoenolpyruvate to ADP

The Overall Balance Sheet Shows a Net Gain of ATP

• PASTEUR EFFECT: 15 times, in anaerobic.• REGULATION: allosteric, hormonal, gene

expression• GLYCOLYSIS AND CANCER: (10 times more),

anaerobic glycolysis, low mitochondria, high production of glycolytic enzymes.

SUMMARY

Entry of other sugars into glycolytic pathway

fructose

• Present in free form in many fruits• Hydrolysis of sucrose in the intestines of verts• In muscle and kidney; fructose

phosphorylated by hexokinase to F-6-P

IN THE LIVER

• GLYCERALDEHYDE- triose kinase • DHAP- triose phosphate isomerase

galactose

Lactic acid fermentation

EthanolFermentation

Some TPP-Dependent Reactions