Download Carbohydrate Metabolism

Carbohydrate
Metabolism
I. Introduction:
A. More than 60% of our foods are carbohydrates.
Starch, glycogen, sucrose, lactose and cellulose are
the chief carbohydrates in our food. Before
intestinal absorption, they are hydrolysed to hexose
sugars (glucose, galactose and fructose).
Glucose Oxidation
major Pathway
Cellular Respiration
Food
O2
(Fuel of energy)
Respiration
O2
H2O
Energy
+
CO2
Cellular Activities
Organic compounds + O2
Energy + CO2 + H2O
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.
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).
D. Energy (ATP) production of glycolysis:
ATP production = ATP produced - ATP utilized
In the energy investment phase, ATP provides •
activation energy by phosphorylating glucose.
This requires 2 ATP per glucose. –
In the energy payoff
phase, ATP is
produced by
substrate-level
phosphorylation
and NAD+ is
reduced to NADH.
•
2 ATP (net) and •
2 NADH are produced
per glucose.
Fig. 9.8
Fig. 9.9a
Energy Investment Phase (steps 15)
Fig. 9.9b
Energy-Payoff Phase (Steps 6-
Steps of
Glycolysis
Contd…
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).
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.
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
Substrate level phosphorylation:
This means phosphorylation of ADP to ATP at the reaction itself .in
glycolysis there are 2 examples:
- 1.3 Bisphosphoglycerate + ADP give 3 Phosphoglycerate + ATP
- Phospho-enol pyruvate + ADP give 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.
Oxidative phosphorylation produces almost 90% of the –
ATP generated by respiration.
Some ATP is also generated in glycolysis and the •
citric acid cycle by substrate-level phosphorylation.
Ultimately 38 ATP are •
produced per mole of
glucose that is degraded to
carbon CO2 and H2O by
Here an enzyme –
transfers a phosphate
group from an
organic molecule
(the substrate)
to ADP, forming
ATP.
Fig. 9.7
Biological importance (functions) of glycolysis:
1. Energy production:
a) anaerobic glycolysis gives 2 ATP.
b) aerobic glycolysis gives 8 ATP.
2. Oxygenation of tissues:
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.
Reversibility of glycolysis (Gluconeogenesis):
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.
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.
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.
Overview of metabolism of carbohydrates
Blood
glucose
All Monosaccharides
Glucose in tissues
Metabolised in the following pathways
Gluconeogenesis
Glycolysis
Oxidation
Glycogenesis
Non-carbohydrates
Glycogenolysis
Pyruvate + ATP
Aerobic
Anaerobic
Glycogen
TCA cycle
Riboses + NADPH
Lactate
CO2
Pentose
phosphate
pathway
Electron
transport
ATP + H2O