The Glycolysis Pathway:

 

Dehydrogenase (DH): "oxidation-reduction" reactions, look for NADH or FADH2

Kinase: "Substrate Level Phosphorylation"

Overall Pathway:

Glucose is metabolized to pyruvate.

All intermediates carry phosphate groups to lock them into the cell (stops diffusion).

Hexokinase / Glucokinase: both irreversible

Glucose + ATP ----> Glucose-6-phosphate + ADP

Hexokinase:

Catalyzes the phosphorylation of hexoses in general and is found in all cells that metabolize glucose.

Has a low Km (high affinity) so that it is active even at low glucose concentrations.

Glucokinase:

Glucose specific, found in liver.

Has a high Km (low affinity) to ensure a n appropriate response to elevation of glucose from the diet.

Phosphofructokinase-1 (PFK-1): irreversible

Fructose-6-phosphate + ATP ------> Fructose-1,6-bisphosphate + ADP

Rate-Limiting, Major Regulated Step.

Aldolase:

Fructose-1,6-bisphosphate <----> Dihydroxyacetone phosphate +Glycerladehyde-3-phosphate

Completes the first phase of glycolysis.

These trioses are interconverted by triose phosphate isomerase ------------>

To produce a single product, glyceraldehyde-3-phosphate.

Two molecules of glyceraldehyde-3-phosphate continue through glycolysis.

Glyceraldehyde-3-phosphate Dehydrogenase: Oxidation-Reduction

Glyceraldehyde-3-phosphate + NAD+ + Pi <---> 1,3-Bisphosphoglycerate + NADH

NADH formed must be reoxidized to regenerate NAD+ to sustain glycolysis.

Energy released from this reaction is conserved as a high energy phosphate bond in 1,3-bisphosphoglycerate.

Inorganic phosphate, rather than ATP, provides the source of the phosphoryl group.

Aerobic Conditions:

Mitochondrial systems oxidize NADH and produce ATP.

Phosphoglycerate Kinase: "Substrate Level Phosphorylation"

1,3-bisphosphoglycerate + ADP <----> 3-phosphoglycerate + ATP

1,3-Bisphosphoglycerate is a high energy intermediate that drives the phosphorylation of ADP to ATP.

Remember: Two molecules are proceeding through glycolysis, so 2 ATP.

Pyruvate Kinase: "Substrate Level Phosphorylation"

Phosphoenolpyruvate + ADP -------> Pyruvate + ATP

Irreversible, Highly Regulated.

Produce 2 ATP.

Lactate Dehydrogenase: "Anaerobic"

Pyruvate + NADH ----> Lactate + NAD+

This step regenerates NAD+ for glyceraldehyde-3-phosphate dehydrogenase or glycolysis would STOP.

H4: heart isozyme, high affinity for lactate (low Km), allosterically inhibited by pyruvate.

When pyruvate is high oxidizes to Acetyl CoA.

M4: muscle isozyme, produces lactate in muscle when pyruvate is high.

Energy Yield:

Anaerobic (i.e. RBC): Pyruvate ---> Lactate, 2 ATP per glucose molecule.

Aerobic: Mitochondrial oxidation of NADH via electron transfer shuttles.

NADH ----> 2 ATP, a-glycerol phosphate shuttle (4 ATP per glucose)

NADH ----> 3 ATP, malate-aspartate shuttle (6 ATP per glucose)

 

Fructose Metabolism:

Occurs in liver.

Fructose

 

Galactose Metabolism:

Occurs in liver.

Galactose

UDP-Glucose is an activated form of glucose found as an intermediate in glycogen formation.

UDP-Glucose is recycled from UDP-Galactose thus, there is no NET change in concentration of this compound.

Fructose and Galactose Energy Production: still 2 ATP.

(Fructose enters at glyceraldehyde-3-phosphate)

(Galactose enters at glucose-6-phosphate)

© Dr. Noel Sturm 2020


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