Introductory Biochemistry

Glucose Metabolism
Glucose and Glycolysis

Glucose occupies a central position in the metabolism of most cells.

The Pathways of Glucose Metabolism

GLUCOSE
glycogen synthesis

GLYCOGEN
glycogenolysis

GLYCOLYSIS

GLUCONEOGENESIS

PYRUVATE

You will be given this scheme on your final exam

The Structures of Glucose

Glucose is a six-carbon compound with one aldehyde group and five hydroxyl groups..

which cyclizes to form a 6-membered ring.

Glycolysis

Occurs in the cytosol. Serves as the first step in the complete oxidation of glucose to CO2 and H2O.

Production of a small amount of ATP.

Provides building blocks for the synthesis of cellular molecules. Can occur under aerobic OR anaerobic conditions.

Typically occurs under aerobic conditions

Can only metabolize fat aerobically

Glycolysis
energy Investment
Hexose phase

2x 2x 2x 2x 2x 2

Energy Payout
Triose phase

Phosphorylation reactions

+ H+

The Reaction Catalyzed by Hexokinase: first ATP investment

Glucose and Fructose are Structural Isomers

aldehyde ketone

The Reaction Catalyzed by PFK-1: second ATP investment

+ H+

The reaction catalyzed by PFK-1 is the committed step in glycolysis

HK

Isomerase

PFK-1

Glucose

G6P

F6P
Committed step

F-1,6-BP

Glycogen

The Lysis in Glycolysis

The Production of Two Molecules of Glyceraldehyde 3-Phosphate

Lysis
Via two separate reactions (lysis and isomerization), two molecules of GAP are produced from one molecule of fructose-1,6biphosphate.

Isomerization

C6

C6
C6 C6 C3 C3

One Molecule of Glucose Produces Two Molecules of GAP

C3

C3
C3 C3 C3 C3

C3 C3 C3 C3 C3

The Oxidation Reaction in Glycolysis

R group

1,3-BPG is a high-energy intermediate

1,3-BPG has a large phosphoryltransfer potential

Synthesis of ATP
Paying back the debt

This reaction happens twice for every glucose molecule

This is a phosphoryl-transfer reaction and, specifically, a substrate-level phosphorylation (SLP) reaction.

Coupled reaction

An Isomerization

The Generation of PEP a highenergy intermediate

This is a dehydration reaction.

The Reaction Catalyzed by Pyruvate Kinase SLP reaction

+ H+ +

In this reaction, large amounts of free energy are released during the conversion of enolpyruvate to pyruvate.

Balanced Equation for Glycolysis

Glucose + 2ATP + 2NAD+ + 2Pi + 4ADP +2H+

In glycolysis, the NET yield of ATP molecules per molecule of glucose is 2.

NET YIELD = GROSS YIELD INPUT 2 ATP = 4 ATP 2 ATP

The rate of glycolysis is tightly regulated in all cells.

Regulation is important to ensure that:

Cells energy needs met. Fuel is not wasted.

There are appropriate levels of intermediates required for other purposes.

The rate of flux through metabolic pathways is regulated by four major processes:

Substrate availability. Alteration of enzyme activity. Alteration of amount of enzyme.

Compartmentation.

Hexokinase is inhibited by its product, G-6P product inhibition

Glucose
Hexokinase

Glucose-6-phosphate

PFK-1 is allosterically regulated by ADP/AMP and PEP

Glucose
ATP

Fructose-6-P

ADP/AMP

The concentrations of ADP/AMP in a cell is a good indicator of the need for ATP.

Fructose-1,6-BP
Feedback Inhibition

Phosphoenolpyruvate

Elevated PEP levels signal that the products of glycolysis are not being consumed.

Pyruvate

Pyruvate kinase is an allosteric enzyme: feedforward activation by F-1,6-BP

Pyruvate kinase

PFK-1 and PK both inhibited by ATP

Most enzymes catalyze

reversible reactions Synchronous regulation of irreversible reactions

Glycolysis is regulated by signals outside the cell as well as by signals inside the cell
by insulin by glucagon

The Reactions of Glycolysis

1.

glucose + ATP glucose-6-phosphate F-6-P + ATP F-1,6-BP DHAP GAP + NAD+ + Pi 1,3-BPG + ADP 3-phosphoglycerate 2-phosphoglycerate PEP + ADP + H+

glucose-6-phosphate + ADP + H+ ATP Investment fructose-6-phosphate Isomerization fructose-1,6-bisphosphate + ADP+ H+ ATP Investment GAP + DHAP Lysis GAP Isomerization 1,3-BPG + NADH + H+ Oxidation 3-phosphoglycerate + ATP Substrate level phosphorylation (SLP) 2-phosphoglycerate Isomerization phosphoenolpyruvate + H2O Dehydration pyruvate + ATP SLP

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