Carbohydrate Metabolism

Glycolysis, Krebs Cycle, ETS, Gluconeogenesis

Pentose Phosphate Pathway (PPP)
Metabolism – refers to entire set of life sustaining
chemical reactions that occur organisms.
The carbohydrate is utilized by cells mainly as glucose.
– Catabolism – break down complex molecules
• Exergonic – produce more energy than they consume
– Anabolism – combine simple molecules into complex
ones
• Endergonic – consume more energy than they produce
•Adenosine triphosphate (ATP)
– “energy currency”
• Is the energy form stored in cells.
ADP + P + 7.3 kcal/mole (31 kJ/mole) ↔ ATP
• Is obtained from the oxidation of food.
• Consists of adenine (nitrogen base), a ribose sugar, and
three phosphate groups.
• Requires 7.3 (31 kJ) per mole to convert ADP + Pi
to ATP.
 Role of ATP in linking anabolic and
catabolic reactions

Enzymatic Reaction
 Energy transfer
• Oxidation-reduction or redox reactions
– Oxidation – removal of electrons
• Dehydrogenation – removal of hydrogens
• Liberated hydrogen transferred by coenzymes
– Nicotinamide adenine dinucleotide (NAD)
– Flavin adenine dinucleotide (FAD)
• Glucose is oxidized
– Reduction – addition of electrons

Copyright 2009, John Wiley & Sons, Inc.

 3 Mechanisms of ATP generation
1. Substrate-level phosphorylation
• Transferring high-energy phosphate group from
an intermediate directly to ADP
2. Oxidative phosphorylation
• Remove electrons and pass them through
electron transport chain to oxygen
3. Photophosphorylation
• Only in chlorophyll-containing plant cells

Copyright 2009, John Wiley & Sons, Inc.

Some important fates of glucose
Stage 1: Digestion of Carbohydrates
In Stage 1, the digestion of carbohydrates
 Begins in the mouth where salivary amylase breaks
down polysaccharides to smaller polysaccharides
(dextrins), maltose, and some glucose.
 Continues in the small intestine where pancreatic
amylase hydrolyzes dextrins to maltose and glucose.
 Hydrolyzes maltose, lactose, and sucrose to
monosaccharides, mostly glucose, which enter the
bloodstream for transport to the cells.

7
Digestion of Carbohydrates

Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings

GLYCOLYSIS (EMBDEN-MEYERHOF PARNAS PATHWAY [EMP])
glycosG = sugar (sweet); lysisG = dissolution
GLYCOLYSIS is the sequence of 10 enzyme catalyzed reactions that converts
glucose into pyruvate with the simultaneous production of ATP.
Site of reaction: All the reaction steps take place in the cytoplasm or extra mitochondrial
part of the cell.
Glycolysis……
– Splits 6-carbon glucose into TWO 3-carbon molecules of
pyruvic acid
– Consumes 2 ATP but generates 4ATP,
Net Gain=2 ATP
– 10 reactions
– Fate of pyruvic acid depends on oxygen availability
• If oxygen is scarce (anaerobic), reduced to lactic acid
• If oxygen is plentiful (aerobic), converted to acetyl coenzyme A

Two Phases of Glycolysis

These reactions are grouped under 2 phases, phase I and II
A. Phase I or Preparatory Phase.
It consists of the first 5 steps. In these reactions, glucose is enzymatically phosphorylated
by ATP (first at carbon 6 and later at carbon 1) to yield fructose 1,6-diphosphate which is
then split in half to yield 2 moles of the 3-carbon compound, glyceraldehyde 3-phosphate.
The first phase of glycolysis, thus, results in cleavage of the hexose chain. This phase
requires an investment of 2ATP moles to activate (or prime) the glucose mole and
prepare it for its cleavage into two 3- carbon pieces. Besides glucose, other hexoses such
as D-fructose, D-galactose and D-mannose may also convert into glyceraldehyde 3-
phosphate.
B. Phase II or Payoff Phase. The last 5 reactions of glycolysis constitute this phase.
This phase represents the payoff of glycolysis, in which the energy liberated during
conversion of 3 moles of glyceraldehyde 3-phosphate to 2 moles of pyruvate is
converted by the coupled phosphorylation of 4 moles of ADP to ATP. Although 4
moles of ATP are formed in phase II, the net overall yield is only 2 moles of ATP per
mole of glucose oxidized, since 2 moles of ATP are invested in phase I. The phase II
is, thus, energy conserving.
 H
CH2O P C O
C O Triose Phosphate HCOH
6
CH2OH CH2OH Isomerase CH2O P
5 O
H H H Dihydroxyacetone Glyceraldehyde
5
4 1 phosphate 3-phosphate
HO OH H OH 2 NAD+ + 2 P
3 2 Glyceraldehyde 3- 6
H OH Glucose (1 molecule) phosphate 2 NADH + 2H+
dehydrogenase CH2O P
Hexokinase ATP
HCOH
1
ADP C O P 1, 3-Bisphosphoglyceric acid
(2 molecules)
O
P OH2C
Phosphoglycerate 2 ADP
First Substrate level
O
H
H
H
kinase
7
2 ATP
phosphorylation
OH H CH2O P
HO OH
HCOH 3-Phosphoglyceric acid
Phosphoglucose H OH Glucose 6-phosphate
(2 molecules)
COOH
Isomerase 2 Phosphoglycerate
8
P OH2C 6 mutase
O 1
CH2OH
CH2OH
5
HCO P 2-Phosphoglyceric acid
2
(2 molecules)
H H HO COOH
OH
4
OH
3
Enolase 9
H Fructose 6-phosphate
CH2 Water
Phosphofructokinase 3
ATP
C O P Phosphoenolpyruvic acid
ADP (2 molecules)
COOH
P OH2C 2 ADP Second Substrate level
O
CH2O P Pyruvate Kinase 10
2 ATP phosphorylation
H H HO
OH CH 3
Aldolase OH H Fructose 1, 6-bisphosphate C O
Pyruvic acid
COOH (2 molecules)
4
Coenzyme NAD+
NAD+ (nicotinamide adenine dinucleotide)
 Participates in reactions that produce a carbon-
oxygen double bond (C=O).
 Is reduced when an oxidation provides 2H+ and 2e-.
Oxidation O
||
CH3—CH2—OH CH3—C—H + 2H+ + 2e-
Reduction
NAD+ + 2H+ + 2e- NADH + H+

16
Coenzyme FAD
FAD (flavin adenine dinucleotide)
 Participates in reactions that produce a carbon-carbon
double bond (C=C).
 Is reduced to FADH2.

Oxidation
—CH2—CH2— —CH=CH— + 2H+ + 2e-

Reduction
FAD + 2H+ + 2e- FADH2

17
Hexokinase and pyruvate kinase are regulated to match PFK-1

Hexokinase is feedback inhibited by G6P

Pyruvate kinase is feed-forward activated by F1,6-BP

18
 Glucokinase
 Isozyme in liver
 Higher Km
 Not inhibited by glucose-
6-P
 Why? Liver serves to
modulate blood sugar
 Pyruvate Kinase
 Third irreversible step
 Inhibited by ATP
 Activated by F1,6bP
 Feed-forward
activation
 PK is active in
dephosphorylated
state and inactive
in phosphorylated
state.
 Glucagon inhibits
hepatic glycolysis
 Curve becomes
hyperbolic
 PK in Liver

 Regulated by glucagon

The pancreas releases glucagon when the concentration of insulin (and

indirectly glucose) in the bloodstream falls too low. Glucagon causes the liver
to convert stored glycogen into glucose, which is released into the
bloodstream
Pasteur Effect
 the inhibition of glycolysis by oxygen
 The level of glycolytic intermediates from fructose-61,6,-
bip onwards decrease while the earlier intermediates
accumulate.

 Crabtree effect
 The phenomenon of inhibition of oxygen consumption by
the addition of glucose to tissues having high aerobic
glycolysis.
 Increase competition of glycolysis for inorganic phosphate
and NAD which limits their availability for phosphorylation
and oxidation.
22
The acetyl groups are relatively high-energy

In the next stage of catabolism (the citric acid cycle), the energy contained in
the acetyl groups is used to produce more NADH and more ATP. 23
 Citric Acid cycle or
Tricarboxylic Acid cycle
or Krebs Cycle
FADH2
FAD
Regulation of CAC:
Rate controlling enzymes:
Citrate synthatase
Isocitrate dehydrogenase
-keoglutaratedehydrogenase

Regulation of activity by:

Substrate availability
Product inhibition
Allosteric inhibition or activation by other
intermediates