Download Carbohydrate Metabolism Updated

Dr. Bassima Sadiq jaff
DIGESTION, ABSORPTION AND TRANSPORT
OF CARBOHYDRATES
Case History 1
A 12-year-male had complained of abdominal discomfort, a
feeling of being bloated, increased passage of urine and
development of diarrhea after taking milk.
Questions
a. Name the probable disorder.
b. Cause of disorder.
c. What will you suggest the patient to relieve the
symptoms?
Figure 12.2: Transport of glucose, fructose,
galactose and mannose
METABOLIC FATE OF CARBOHYDRATES
The major metabolic pathways of carbohydrates are :
• Glycolysis:The oxidation of glucose to pyruvate and lactate.
• Citric acid cycle:(Krebs cycle or tricarboxylic acid cycle)
oxidation of acetyl-CoA to CO2 and water.
• Gluconeogenesis:Synthesis of glucose from noncarbohydrate
substances such as lactate, glycerol, glucogenic amino acids, etc.
• Glycogenesis:Synthesis of glycogen from glucose.
• Glycogenolysis:Breakdown of glycogen to glucose.
• Hexose monophosphate Shunt(HMP Shunt): It is an alternative
pathway for oxidation of glucose. Some pentoses can also be
oxidized through this pathway.
• Uronic acid pathway:Glucose is oxidized to glucuronic acid.
• Galactose metabolism:Galactose is converted to glucose.
• Fructose metabolism:Fructose is converted to glucose or
metabolized in liver.
Reactions of Glycolysis
Difference between hexokinase and
glucokinase

Regulation of Glycolysis

regulated at 3 steps which are
irreversible,these reactions are
catalyzed by:
1. Hexokinase and glucokinase
2. Phosphofructokinase-I
3. Pyruvate kinase.
• Pyruvate kinase is an inducible enzyme that increases in
concentration with high insulin levels and decreases with
glucagon
• It is activated by fructose-1, 6-bisphosphate and inactivated by
ATP.
Case History
An obese person came to the hospital with complaintsof
polyuria, thirst, weakness and increased appetite.On
investigations, he was diagnosed having diabetes mellitus.
Questions
a. What is the cause of diabetes mellitus?
b. Give names of different types of diabetes mellitus.
c. What is glucosuria? Name different types of
glucosuria.
d. What is the normal blood sugar level?
Case history
At a village fete, a local charity group was fund raising by
performing certain
sideroom tests. An 11-year-old boy was found to have a blood
glucose of
14.4 mmol/L. His family was concerned, and an hour later his
cousin, a recently
diagnosed diabetic, confirmed the hyperglycaemia with his
home
monitoring equipment, and found glycosuria +++.
What is the significance of these findings?
ALTERNATE FATES OF PYRUVATE
A. Oxidative decarboxylation of pyruvate
B. Carboxylation of pyruvate to oxaloacetate
C. Reduction of pyruvate to ethanol (microorganisms)
*(PDH complex) is a multimolecular aggregate of three
enzymes,
pyruvate dehydrogenase (PDHor E1, also called a
decarboxylase), dihydrolipoyl transacetylase(E2), and
dihydrolipoyl dehydrogenase(E3).
*Coenzymes:The PDH complex contains five coenzymes
that act as carriers or oxidants for the intermediates of the
reactions
E1 requires thiamine pyro phos phate (TPP),
E2 requires lipoic acid and CoA.
E3 requires FAD and NAD+
.
RAPOPORT LUEBERING
CYCLE
2-3 BPG regulates the binding of O2to hemoglobin.
• The presence of BPG significantly reduces the affinity
of hemoglobin for oxygen.
• This reduced affinity releases oxygen efficiently in
peripheral tissues.
• One molecule of 2-3 BPG binds in the central cavity
of deoxyhemoglobin. It binds with β-chains through
ionic bonds.
• In HbA, the binding site is made up of six +ve
charges of amino acids of β-globin chains and five
-ve charges of phosphate groups of 2-3 BPG
• The level of 2-3 BPG increases, such compensatory increase
occurs in:
– Individuals who live at high altitudes
– Patients with chronic obstructive pulmonary
disease (COPD) like emphysema
– Anemias
– Cardiac failure.
Citric acid cycle
Production of ATP in citric acid
cycle
Significance of Citric Acid Cycle
•provide energy in the form of ATP.
• the final common pathway for the oxidation of carbohydrates,
lipids, and proteins are all metabolized to acetyl-CoA or
intermediates of the cycle.
• an amphibolic process.Citric acid cycle has a dual function, it
(catabolism and anabolism).
pathways originate from the cycle:
• Gluconeogenesis:All major members of the citric
acid cycle from citrate to oxaloacetate are glucogenic.
They can give rise to glucose by gluconeogenesis
• Transamination :Oxaloacetate and α-ketoglutarate
respectively, serve as precursors for the synthesis
of aspartate and glutamate by transamination which
in turn are used for the synthesis of other non essential amino
acids, purines and pyrimidines.
• Fatty acid synthesis :Mitochondrial citrate is transported
to the cytosol, where it is cleaved to provide acetyl-CoA
for the biosynthesis of fatty acids and steroids.
• Heme synthesis :Succinyl-CoA (intermediate of
TCA cycle) +glycine
Amphibolic role of the citric acid cycle
Pathway of gluconeogenesis
The synthesis of glucose from non carbohydrate
precursors is called gluconeogenesis
Cori cycle or lactic acid cycle and glucose alanine cycle.
Because muscle is incapable of synthesizing urea, most of the
ammonia formed by protein catabolism is transferred to
pyruvate to form alanine by transamination reaction.
• Alanine enters the blood and is taken up by the liver.
• In the liver, the amino groups of alanin is removed
to form urea, and the resulting pyruvate is converted
to glucose by gluconeogenesis which is then transported to the
muscle, where it is oxidized to pyruvate.
• The pyruvate acts again as the acceptor for another
amino group.