Transcript Carbohydrate Metabolism-1

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
1. Glycolysis
2. Citric acid cycle
3. Gluconeogenesis
4. Glycogen metabolism
(a) Glycogenesis (b) Glycogenolysis
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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
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Energy-Payoff Phase (Steps 6-10)
Energy production of glycolysis:
ATP produced
ATP utilized
In absence of oxygen
(anaerobic
glycolysis)
4 ATP
(Substrate level
phosphorylation)
2ATP from 1,3 DPG.
2ATP from
phosphoenol
pyruvate
2ATP
2 ATP
From glucose to
glucose -6-p.
From fructose -6-p to
fructose 1,6 p.
In presence of
oxygen (aerobic
glycolysis)
4 ATP
(substrate level
phosphorylation)
2ATP from 1,3 BPG.
2ATP from
phosphoenol
pyruvate.
2ATP
6 ATP
-From glucose to
Or
glucose -6-p.
8 ATP
From fructose -6-p to
fructose 1,6 p.
+ 4ATP or 6ATP
(from oxidation of 2
NADH + H in
mitochondria).
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Net energy
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:
1) It is important in other tissues patriculary liver and heart.
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2) The final energy produced
is 6 ATP.
Differences between aerobic and
anaerobic glycolysis:
Aerobic
Anaerobic
1. End product
Pyruvate
Lactate
2 .energy
6 or 8 ATP
2 ATP
3. Regeneration of
NAD+
Through respiration
chain in mitochondria
Through Lactate
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 noncarbohydrate 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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Fig. 9.10
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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
in NADH and
FADH2
Pyruvic acid
Glucose
Glycolysis
Electron
Transport Chain
Krebs
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
PPi
Pyrophosphatase
2 Pi
UDP-Glucose
UTP
Glucose-6-P
UDP-Glucose
Pyrophosphorylase
UDP
Glycogen (Glucose)n+1
Glucose-1-P
Phosphoglucomutase
Glycogen
Phosphorylase
Glycogen
(Glucose)n
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Glycogen
Synthase
Glycogen
(Glucose)n
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Pi
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
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as brain cells.