2. Glucose metabolism
Importance of Glucose:
1. Glucose is the preferred source of energy for most
of the body tissues. Brain cells derive energy
mainly from glucose.
2. When glucose metabolism is deranged, life-
threatening conditions may occur. A minimum
amount of glucose is always required for normal
functioning.
3. Normal fasting plasma glucose level is 70 to 110
mg/dl. After a heavy carbohydrate meal, in a
normal person, this level is below 150 mg/dl.
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3. Glucose is used in
• Oxidation:
The pathways for oxidation of glucose are classified
into two main groups:
A. The major pathways which are mainly for
energy production:
1. Glycolysis.
2. Citric acid cycle (CAC).
B. The minor pathways for oxidation which are not
for energy production:
1. Hexose monophosphate shunt (HMS).
2. Uronic acid pathway.
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4. • II. Conversion to biologically active
substances as:
1. Galactose: which is essential for formation of
lactose, glycolipids, mucopolysaccharides, ...etc.
2. Fructose: needed for nutrition of sperms.
3. Amino sugars.
4. Non-essential amino acids.
5. Fatty acids.
6. Ribose-5-P.
7. Glucuronic acid.
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5. • III. Storage of glucose:
1. As glycogen in the liver and muscles mainly.
2. As triglycerides (TG), mainly in adipose tissues.
• IV. Excretion of glucose in urine:
When blood glucose level exceeds a certain limit
(renal sugar threshold), it will pass to urine. This
will occur when blood glucose level is above 180
mg/dl and this is known as glucosuria.
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6. Glycolysis
(Embden-Meyerhof Pathway)
Importance of the pathway
• In this pathway glucose is converted to pyruvate
(aerobic condition) or lactate (anaeroboic
condition), along with production of a small
quantity of energy.
• All the reaction steps take place in the cytoplasm. It
is the only pathway that is taking place in all the
cells of the body.
• Glycolysis is the only source of energy in
erythrocytes.
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9. Importance of glycolysis
• I-Energy production :
• 1. Under aerobic conditions:
Glucose ------→ 2 Pyruvate + 8 ATP.
For tissues that have mitochondria, glycolysis
is considered a preparatory step for complete
oxidation via citric acid cycle since pyruvate is
transported into the mitochondria to provide
oxaloacetate or active acetate where it is
oxidized by CAC for more energy.
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10. • The hydrogens of NADH produced by
glycolysis are transported to the mitochondria
mainly to be oxidized by electron transport
chain (ETC).
• 2. Under anaerobic conditions:
Glucose ------→ 2 lactate + 2 ATP
Pyruvate is reduced to lactate in a reversible
reaction catalyzed by lactate dehydrogenase
(LDH).
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11. • This occurs in muscles during severe exercise
(hypoxic conditions) and in tissues that lack
mitochondria as RBCs and lens.
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12. Cori’s cycle or lactic acid cycle
• In an actively contracting muscle, only about
8% of the pyruvate is utilized by the citric acid
cycle, and the remaining molecules are
therefore reduced to lactate.
• The lactic acid thus, generated should not be
allowed to accumulate in the muscle tissues.
• The muscle cramps, often associated with
strenuous muscular exercise, are through to
be due to lactate accumulation.
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13. • This lactate diffuses into the blood. During exercise,
blood lactate level is increased appreciably.
• Lactate then reaches liver, where it is oxidized to
pyruvate.
• It is then taken up through gluconeogenesis
pathway, and becomes glucose which can enter into
blood and then taken to muscle.
• This cycle is called Cori’s cycle, by which the Lactate
is efficiently reutilized by the body.
• Carl Cori and Gerty Cori were awarded Nobel prize
in 1947.
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15. glycolysis
Regulation of
Hormonal regulation of glycolysis:
• a) Glucagon : is secreted in hypoglycemia or in
carbohydrate deficiency. It affects liver cells mainly
as follows:
It acts as inhibitors for glycolytic key enzymes
(glucokinase,PFK-1, pyruvate kinase).
• b) Insulin: It is secreted in hyperglycemia and after
carbohydrates feeding, it causes:
Stimulation of glycolytic key enzymes.
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17. Inhibitors of glycolysis:
1- 2- deoxyglucose inhibits
hexokinase.
2- Mercury and iodoacetate inhibit
glyceraldehyde-3-P dehydrogenase.
3- Fluoride inhibits enolase by removal
of Mg2+ as Mg fluoride.
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18. Pyruvate as a junction point
Pyruvate occupies an important junction
between various metabolic pathways. It may be
decarboxylated to acetyl-CoA which enters the
TCA cycle, or may be utilized for fatty acid
synthesis.
Pyruvate may be carboxylated to oxaloacetate
which is used for gluconeogenesis.
Pyruvate dehydrogenase step is the committed
step towards oxidation of glucose.
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20. Citric acid cycle (CAC)
or Tricarboxylic Acid Cycle (TCA)
or Krebs Cycle
Definition:
It is a series of reactions in mitochondria, that
brings about the catabolism of acetyl residues,
liberating hydrogen equivalents which upon
oxidation, leads to the release of energy.
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22. Functions of the Citric Acid Cycle
1. It is the final common oxidation pathway that
oxidises acetyl CoA to CO2.
2. Energy production, every one mole of acetyl- CoA
produces 12 moles of ATP.
3. It is the source of reduced coenzymes that provide
the substrate for the respiratory chain.
4. It acts as a link between catabolic and anabolic
pathway (amphibolic role).
5. It provides precursors for synthesis of amino acids
and nucleotides.
6. Components of the cycle have direct or indirect
controlling effects on key enzymes of other
pathways.
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23. Total ATP produced from complete oxidation of
one molecule of glucose during glycolysis,
oxidative decarboxylation and CAC :
Glycolysis G → 2PA 8 ATP
Oxidative decarboxylation 2PA → 2 acetyl CoA 6 ATP
(2 NADH + H+ ×3)
Oxidation of 2 acetyl CoA in CAC → (12 ATP ×2) 24 ATP
-------------------
38 ATP
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24. Inhibitors of CAC
1- Fluorocitrate inhibits aconitase.
2- Mercury and arsenite inhibit pyruvate and α–
ketoglutarate dehydrogenase complex.
3- Malonic acid inhibits succinic acid
dehydrogenase.
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25. Gluconeogenesis
• i. It is the process by which new glucose is
synthesized from noncarbohydrate precursors like
lactate, glycerol and glucogenic amino acids.
• ii. It occurs mainly in the liver.
• iii. Gluconeogenesis involves several enzymes of
glycolysis, but it is not a reversal of glycolysis.
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