Glycolysis, Gluconeogenesis,

Glycogen Metabolism, Pentose

Phosphate Pathway
Chapter 13

Overview of Energy
Metabolism

12.4

Fermentation and Respiration

glucose
(anaerobic)

Fermentation

Fermentation
products
(aerobic)

O2

Respiration

CO2 + H2O

Glucose
Fermentation

13.3

2 phases of glycolysis
Chemical strategy:
1. add phosphoryl groups to
glucose (low phosphate
transfer potential bonds) =
priming
2. chemically convert low
energy phosphorylated
intermediates into
compounds with high
phosphate group-transfer
potential
3. chemically couple the
energy-yielding hydrolysis of
these to ATP synthesis

13.2

Overview of
glycolysis

13.4

Reaction 1: Hexokinase

glucokinase
(liver)

Reaction 1: Hexokinase

Hexokinase isozymes

p. 525

Reaction 2:
glucose-6-phosphate
isomerase

Reaction 3:
Phosphofructokinase (PFK)

Committed
step for
glycolysis!!

Reaction 4: Aldolase

(DHAP)

(GAP)

Reaction 4: aldolase

13.5

Reaction 5: Triose phosphate isomerase

2 phases of glycolysis
Chemical strategy:
1. add phosphoryl groups to
glucose (low phosphate
transfer potential bonds) =
priming
2. chemically convert low
energy phosphorylated
intermediates into
compounds with high
phosphate group-transfer
potential
3. chemically couple the
energy-yielding hydrolysis of
these to ATP synthesis

13.2

Reactions 6-10: Energy Generation Phase

p. 529

Pyridine ring

reversible
2-electron transfers only:

Dissociate from enzymes

NAD+ (nicotinamide
adenine dinucleotide)
lacks this phosphate

p. 486, 488

Glyceraldehyde-3-phosphate dehydrogenase

13.6

Conserves energy of oxidation by coupling exergonic rxn to endergonic rxn:

(Releases
energy)

(Requires
energy)

p.
530

G = -18.8 kJ/mol

Sum of reactions 6 + 7:
G
glyceraldehyde-3-P + Pi + NAD+ ! 1,3-bisphosphoglycerate + NADH + H+

+6.3

1,3-bisphosphoglycerate + ADP ! 3-phosphoglycerate + ATP

-18.8

glyceraldehyde-3-P + Pi + ADP + NAD+ !

3-phosphoglycerate + ATP + NADH + H+

GS = -12.5

Reaction 8: phosphoglycerate mutase

pp. 532-532

Reaction 9: Enolase

glycerol-phosphate + H2O ! glycerol + Pi -15.6

G = -31.4 kJ/mol

Substrate-level
phosphorylation

Pyruvate kinase

p. 79, 533

Glycolysis

12.3

Oxidative
metabolism

12.4

If no oxygen available:

p. 536

Lactate dehydrogenase

13.7

Pyruvate decarboxylase rxn

13.8

Glucose Fermentation

13.3

Energetics of glycolysis (fermentation)

Balance sheet:
glucose + 2Pi + 2ADP ! 2 ethanol + 2CO2 + 2ATP + 2H2O

[Products]
G = G' +RT ln
[Reactants]
o

(compare to G
values in Table 13.1)

13.9

Gluconeogenesis:
synthesis of new glucose

13.10

13.11

Bypass 1: conversion of pyruvate to PEP

p. 542

pyruvate
carboxylase

Acetyl-CoA

oxaloacetate + GTP ! phosphoenolpyruvate + CO 2 + GDP G' = +2.9 kJ/mol

PEP carboxykinase
(PEPCK)

Bypass 1: conversion of pyruvate to PEP

NADH

NAD+

NADH

This pathway
is important in
muscle after
exercise

NAD+

13.12

Net for bypass 1:

pyruvate + ATP + GTP + HCO3- !
PEP + ADP + GDP + Pi + H+ + CO2
Go= + 0.8 kJ/mol
13.11

G ~ -25 kJ/mol

Bypass 2: fructose-1,6-bisphosphatase (FBPase)

Fructose-1,6-bisphosphate + H 2O fructose-6-phosphate + Pi G' = -16.3 kJ/mol

Bypass 3: glucose-6-phosphatase
Glucose-6-phosphate + H 2O glucose + Pi G' = -13.8 kJ/mol

13.11

Energetics of gluconeogenesis
Balance sheet:
2 pyruvate + 4ATP + 2GTP + 2NADH + 2H+ + 4H2O
! glucose + 4ADP + 2GDP + 2NAD+ + 6Pi

G = -33 kJ/mol
(compare with ~ +83 kJ/mol for reversal of glycolysis
from 2 pyruvate)

Keq ~ 363,000 ! highly favorable ! goes to completion