Carbohydrate

Metabolism
An Overview
General Biochemistry-II
(BCH 302)
Dr . Saba Abdi
Asst . Prof. Dept. Of Biochemistry
College Of Science
King Saud University. Riyadh.KSA
 Major Pathways
Glycolysis. 1
Citric acid cycle. 2
Gluconeogenesis. 3
Glycogen metabolism. 4
Glycogenesis )b( Glycogenolysis ( a )

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I. Glycolysis (Embden Meyerhof
Pathway):
A. Definition:
1. Glycolysis means oxidation of glucose to give pyruvate (in the
presence of oxygen) or lactate (in the absence of oxygen).

B. Site:
cytoplasm of all tissue cells, but it is of physiological importance in:
1. Tissues with no mitochondria: mature RBCs, cornea and lens.
2. Tissues with few mitochondria: Testis, leucocytes, medulla of the
kidney, retina, skin and gastrointestinal tract.
3. Tissues undergo frequent oxygen lack: skeletal muscles especially
during exercise.

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C. Steps:
Stages of glycolysis
1. Stage one (the energy requiring stage):
a) One molecule of glucose is converted into two molecules of
glycerosldhyde-3-phosphate.
b) These steps requires 2 molecules of ATP (energy loss)
2. Stage two (the energy producing stage(:
a) The 2 molecules of glyceroaldehyde-3-phosphate are converted into
pyruvate (aerobic glycolysis) or lactate (anaerobic glycolysis(.
b) These steps produce ATP molecules (energy production).

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 Energy Investment Phase (steps 1-5)
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Fig.9.9a
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Fig.9.9b Energy-Payoff Phase (Steps 6-10)
 Energy production of glycolysis:
ATP produced ATP utilized Net energy

In absence of oxygen 4 ATP 2ATP 2 ATP

(anaerobic glycolysis) (Substrate level From glucose to
phosphorylation) glucose -6-p.
2ATP from 1,3 DPG. From fructose -6-p to
2ATP from fructose 1,6 p.
phosphoenol
pyruvate

In presence of 4 ATP 2ATP 6 ATP

oxygen (aerobic (substrate level -From glucose to Or
glycolysis) phosphorylation) glucose -6-p. 8 ATP
2ATP from 1,3 BPG. From fructose -6-p to
2ATP from fructose 1,6 p.
phosphoenol
pyruvate.

+ 4ATP or 6ATP
(from oxidation of 2
NADH + H in
mitochondria).

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E. oxidation of extramitochondrial NADH+H+:
1. cytoplasmic NADH+H+ cannot penetrate mitochondrial membrane,
however, it can be used to produce energy (4 or 6 ATP) by respiratory
chain phosphorylation in the mitochondria.
2. This can be done by using special carriers for hydrogen of NADH+H+
These carriers are either dihydroxyacetone phosphate (Glycerophosphate
shuttle) or oxaloacetate (aspartate malate shuttle).
a) Glycerophosphate shuttle:
1) It is important in certain muscle and nerve cells.
2) The final energy produced is 4 ATP.
3) Mechanism:
- The coenzyme of cytoplasmic glycerol-3- phosphate dehydrogenase

is NAD+.
- The coenzyme of mitochodrial glycerol-3-phosphate dehydogenase is
FAD.
- Oxidation of FADH, in respiratory chain gives 2 ATP. As glycolysis
gives 2 cytoplasmic NADH + H+ 2 mitochondrial FADH, 2 x 2
ATP = 4 ATP.
b) Malate aspartate shuttle:
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1) It is important in other tissues patriculary liver and heart.
 Differences between aerobic and
anaerobic glycolysis:
Aerobic Anaerobic

1. End product Pyruvate Lactate

2 .energy 6 or 8 ATP 2 ATP
3. Regeneration of Through respiration Through Lactate
NAD+ chain in mitochondria formation
4. Availability to TCA in Available and 2 Pyruvate Not available as lactate
mitochondria can oxidize to give 30 is cytoplasmic substrate
ATP

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Importance of lactate production in anerobic
glycolysis:
1. In absence of oxygen, lactate is the end product of glycolysis:

Glucose Pyruvate Lactate

2. In absence of oxygen, NADH + H+ is not oxidized by the

respiratory chain.
3. The conversion of pyruvate to lactate is the mechanism for
regeneration of NAD+.
4. This helps continuity of glycolysis, as the generated NAD+ will be
used once more for oxidation of another glucose molecule.

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Substrate level phosphorylation:
This means phosphorylation of ADP to ATP at the reaction itself .in
glycolysis there are 2 examples:
- 1.3 Bisphosphoglycerate + ADP 3 Phosphoglycerate + ATP
- Phospho-enol pyruvate + ADP Enolpyruvate + ATP

I. Special features of glycolysis in RBCs:

1. Mature RBCs contain no mitochondria, thus:
a) They depend only upon glycolysis for energy production (=2 ATP).
b) Lactate is always the end product.
2. Glucose uptake by RBCs is independent on insulin hormone.
3. Reduction of met-hemoglobin: Glycolysis produces NADH+H+, which
used for reduction of met-hemoglobin in red cells.

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Biological importance (functions) of glycolysis:
1. Energy production:
a) anaerobic glycolysis gives 2 ATP.
b) aerobic glycolysis gives 8 ATP.
2. Oxygenation of tissues:
Through formation of 2,3 bisphosphoglycerate, which decreases the
affinity of Hemoglobin to O2.
3. Provides important intermediates:
a) Dihydroxyacetone phosphate: can give glycerol-3phosphate, which is
used for synthesis of triacylglycerols and phospholipids (lipogenesis).
b) 3 Phosphoglycerate: which can be used for synthesis of amino acid
serine.
c) Pyruvate: which can be used in synthesis of amino acid alanine.
4. Aerobic glycolysis provides the mitochondria with pyruvate, which gives
acetyl CoA Krebs' cycle.

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Reversibility of glycolysis (Gluconeoqenesis):
1. Reversible reaction means that the same enzyme can catalyzes the
reaction in both directions.
2. all reactions of glycolysis -except 3- are reversible.
3. The 3 irreversible reactions (those catalyzed by kinase enzymes) can be
reversed by using other enzymes.
Glucose-6-p Glucose
F1, 6 Bisphosphate Fructose-6-p
Pyruvate Phosphoenol pyruvate
4. During fasting, glycolysis is reversed for synthesis of glucose from non-
carbohydrate sources e.g. lactate. This mechanism is called:
gluconeogenesis.

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As pyruvate enters the mitochondrion, a
multienzyme complex modifies pyruvate to
acetyl CoA which enters the Krebs cycle in the
.matrix
.A carboxyl group is removed as CO2
A pair of electrons is transferred from the
remaining two-carbon fragment to NAD+ to
.form NADH
The oxidized
fragment, acetate,
combines with
coenzyme A to
.form acetyl CoA
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 Kreb Cycle

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 Electron Transport Chain

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 Summary

Mitochondrion

Electrons carried in NADH

Electrons carried
Pyruvic acid
in NADH and
FADH2

Glucose Electron
Krebs Transport Chain
Glycolysis Cycle

Mitochondrion
Cytoplasm

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 Total energy yield
Glycolysis 2 ATP
Krebs Cycle 2 ATP
ETC 32 ATP

Total 36 ATP

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 Glycogen Metabolism
Pyrophosphatase
PPi 2 Pi

UDP-Glucose Glycogen
(Glucose)n
UTP UDP-Glucose Glycogen
Pyrophosphorylase Synthase UDP

Glucose-6-P Glucose-1-P Glycogen (Glucose)n+1

Phosphoglucomutase Glycogen
Phosphorylase

Glycogen Pi
(Glucose)n

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 :Glycogenesis

Glycogenesis is the formation of glycogen from glucose.

Glycogen is synthesized depending on the demand for
glucose and ATP )energy(. If both are present in relatively
high amounts, then the excess of insulin promotes the
glucose conversion into glycogen for storage in liver and
.muscle cells
In the synthesis of glycogen, one ATP is required per
glucose incorporated into the polymeric branched
structure of glycogen. actually, glucose-6-phosphate is
the cross-roads compound. Glucose-6-phosphate is
synthesized directly from glucose or as the end product of
.gluconeogenesis
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 Glycogenolysis

In glycogenolysis, glycogen stored in the liver and muscles,

is converted first to glucose-1- phosphate and then into
glucose-6-phosphate. Two hormones which control
glycogenolysis are a peptide, glucagon from the pancreas
.and epinephrine from the adrenal glands
Glucagon is released from the pancreas in response to low
blood glucose and epinephrine is released in response to
a threat or stress. Both hormones act upon enzymes to
stimulate glycogen phosphorylase to begin glycogenolysis
.and inhibit glycogen synthetase )to stop glycogenesis(

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 .
Glycogen is a highly branched polymeric structure
containing glucose as the basic monomer. First individual
glucose molecules are hydrolyzed from the chain, followed
by the addition of a phosphate group at C-1. In the next
step the phosphate is moved to the C-6 position to give
.glucose 6-phosphate, a cross road compound
Glucose-6-phosphate is the first step of the glycolysis
pathway if glycogen is the carbohydrate source and further
energy is needed. If energy is not immediately needed, the
glucose-6-phosphate is converted to glucose for distribution
. in the blood to various cells such as brain cells

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