Chemistry 501 Handout 14 Glycolysis, Gluconeogenesis, and the ...

Dep. of Chemistry & Biochemistry
Prof. Indig
Chemistry 501
Handout 14
Glycolysis, Gluconeogenesis, and
the Pentose Phosphate Pathway
Chapter 14
Lehninger. Principles of Biochemistry.
by Nelson and Cox, 5 th Edition; W.H. Freeman and Company

Major pathways of glucose utilization

The first phase of glycolysis (the preparatory phase)

The second phase of glycolysis (the payoff phase)
O

The two phases of glycolysis

Three possible catabolic
fates of the pyruvate
formed in glycolysis

1. Phosphorylation of glucose

2. Conversion of glucose 6-phosphate to fructose 6-phosphate

The phosphohexose isomerase reaction
anomeric carbon

3. Phosphorylation of fructose 6-phosphate to
fructose 1,6-bisphosphate

4. Cleavage of fructose 1,6-bisphosphate

The class I aldolase reaction
imine

5. Interconversion of the triose phosphates
Fate of the glucose carbons
in the formation of
glyceraldehyde 3-phosphate

6. Oxidation of glyceraldehyde 3-phosphate to
1,3-bisphosphoglycerate

The glyceraldehyde 3-phosphate dehydrogenase reaction

7. Phosphoryl transfer from
1,3-bisphosphoglycerate
to ADP

8. Conversion of 3-phosphoglycerate to 2-phosphoglycerate

The
phosphoglycerate
mutase reaction

9. Dehydration of 2-phosphoglycerate to phosphoenolpyruvate

10. Transfer of the
phosphoryl group from
phosphoenolpyruvate
to ADP

Entry of
glycogen,
starch,
disaccharides,
and hexoses
into the preparatory
stage of glycolysis
Feeder pathways
for glycolysis

Feeder pathways for glycolysis

Dietary polysaccharides and disaccharides undergo
hydrolysis to monosaccharides

Glycogen breakdown by glycogen phosphorylase

Other monosaccharides enter the glycolytic pathway at several points

Conversion of galactose
to glucose 1-phosphate
Defects in any of the three
enzymes in this phatway
Cause galactosemia in humans
Galactose methabolite involved in
galactokinase-deficiency galactosemia

Fates of pyruvate under anaerobic conditions: Fermentation
Pyruvate is the terminal electron
acceptor in lactic acid fermentation
acidification in muscle
and blood limits the
period of vigorous
activity
no net change in
NAD + or NADH

Ethanol is the reduced product in ethanol fermentation
tightly bound coenzyme, thiamine pyrophosphate
Industrial-scale fermentations yield a variety of
common foods and industrial chemicals

The alcohol dehydrogenase reaction

Thiamine pyrophosphate (TPP) and its role in pyruvate decarboxylation

Thiamine pyrophosphate

Gluconeogenesis
Carbohydrate synthesis
from simple precursors

Opposing pathways of
glycolysis
and
gluconeogenesis
in rat liver

Synthesis of phosphoenolpyruvate
from pyruvate

Role of biotin in the
pyruvate carboxylase
reaction

Alternative paths from
pyruvate
to
phosphoenolpyruvate

Citric acid intermediates and many amino acids are glucogenic
Pyruvate
Amino acid
catabolism
Citrate
Isocitrate
α-ketoglutarate
Succinyl-CoA
Succinate
Fumarate
Malate
C.A.C.
oxaloacetate
C.A.C. Intermediates

Feeder pathways for glycolysis (preparatory phase)

General scheme of the pentose phosphate pathway of glucose oxidation

Oxidative reactions of the
pentose phosphate pathway
NADP +

Nonoxidative reactions of the pentose phosphate pathway
The nonoxidative phase recycles
pentose phosphates
to
glucose 6-phosphate

The first reaction catalyzed by transketolase
thiamine pyrophosphate
General reaction
Transfer of a two-carbon
group from a ketose donor to
an aldose acceptor

The reaction catalyzed
by transaldolase
The second reaction
catalyzed
by transketolase

Role of NADPH in regulating the partitioning of glucose 6-phosphate
between glycolysis and the pentose phosphate pathway

Role of NADPH and glutathione (GSH) in protecting cells against
highly reactive oxygen derivatives