Metabolism of carbohydrate following the curriculum of Medical Biochemistry of MBBS course

1. METABOLISM OF
CARBOHYDRATES
Dr. Farhana Atia
Associate Professor, Biochemistry
Nilphamari Medical College, Nilphamari

2. Pathways involved in the intermediary
metabolism of glucose
• Anabolic pathways
 Glycogenesis
 Gluconeogenesis
 Lipogenesis (if glucose is
excess)
• Amphibolic pathway
– TCA cycle
• Catabolic pathways
– Glycolysis
– Glycogenolysis
– Oxidation of pyruvate to
acetyl co A
– HMP shunt
– Uronic acid pathway

3. Compartments of different metabolic pathway
Cytosol Mitochondria Endoplasmic reticulum
Glycolysis TCA cycle Protein synthesis
HMP shunt RC Oxidative
phosphorylation
Cholesterol synthesis
Glycogenesis β-oxidation
Glycogenolysis Ketogenesis
Lipogenesis Deamination
Transamination
Gluconeogenesis
Urea cycle
Heme synthesis

5. Glycolysis
Oxidation of glucose (or glycogen) to pyruvate or
lactate with the production of ATP by Embden-
Meyerhof pathway is called glycolysis.
2 types-
1. Aerobic glycolysis
2. Anaerobic glycolysis

6. Aerobic glycolysis
• Breakdown of glucose in the cell with mitochondria in
adequate supply of oxygen is called aerobic
glycolysis
• End product: Pyruvate  Acetyl-coA  TCA cycle
 CO2 & H2O

7. Anaerobic glycolysis
• Breakdown of glucose in absence of oxygen is called
anaerobic glycolysis.
• Occurs in cells without mitochondria
• Pathway is same as aerobic except end product
• End product- Lactate (Pyruvate  Lactate)
• Occurs in- •RBC •Renal medulla
•Brain •Skin
•GIT •Skeletal muscle
•Testes •Retina

8. The Pathway of Glycolysis
Salient feature
• Substrate : Glucose or glycogen.
• Product : Pyruvate (aerobic)
Lactate (anaerobic)
• Site : Almost all tissues and cells.
• Compartment: Cytoplasm
• Nature : Catabolic

9. Fluoride inhibit Enolase (in test
tube), so used in lab to prevent
glycolysis
Steps of
Glycolysis

10. Traits Glucokinase Hexokinase
1. Affinity for
glucose
Low
Km value- high
High
Km value- low
2. Specificity Phosphorylated only glucose Non specific, can
phosphorylated any hexose
(glucose, fructose, galactose)
3. Location Liver cell & pancreatic islets
cell
Extrahepatic tissue
4. Action of insulin Stimulated Not affected
5. Action of glucose
6 phosphate
Not affected Allosterically inhibited
6. Net effect Remove glucose from blood
following meal
Maintain blood glucose
concentration

11. Regulation of Glycolysis
Hormonal regulation:
• Insulin:
↑ Activity of enzymes in liver
– Glucokinase
– Phosphofructokinase
– Pyruvate kinase
↑ Conversion of glucose to
pyruvate
• Glucagon
– Opposite effect in fasting &
in DM
– Inhibit the activity of
 Glucokinase
 Phosphofructokinase
 Pyruvate kinase

12. Regulation of Glycolysis
• In well fed-state
↑ Ingestion of glucose
↓
↑ Blood glucose
↓
↑ Release of insulin
↓
↑ Protein phosphatase
activity
• In fasting stage
↑ Blood glucose
↓
↑ Glucagon
↓
↑ c-AMP
↓
↑ Protein kinase
activity of enzyme

13. Energy production in glycolysis
• Aerobic
–In respiratory chain : 5 ATP
–At substrate level : 4 ATP
»Net gain : 9-2= 7 ATP
• Anaerobic
»Net gain : 4-2= 2 ATP

14. Importance of Glycolysis
• Only pathway in all cells of body
• Only source of energy in RBC
• In strenuous exercise, major source of energy.
• Allow tissue to survive anoxic episodes.
• Deficiency of enzyme of glycolysis (eg. Pyruvate kinase)
leads to disease as hemolytic anemia

15. Importance of Glycolysis
• Preliminary steps for complete glucose oxidation.
• Reversible steps are used for gluconeogenesis.
• Provides carbon skeleton for synthesis of
–Non essential amino acid
–Glycerol part of fat

16. Fate of Pyruvate
• In cytoplasm
1. Lactate (reduction)
2. Alanine (transamination)
3. Glucose (gluconeogenesis)
• In mitochondria
1. Acetyl coA (oxidation &
decarboxylation)
2. Oxaloacetate (carboxylation)

17. Sources of Pyruvate
• Glucose (glycolytic pathway)
• Amino acid (transamination)
• Glycerol part of fat

18. Oxidation of pyruvate to acetyl-CoA
The oxidation to pyruvate to acetyl-CoA is the irreversible
route from glycolysis to the citric acid cycle
Pyruvate is transported into the mitochondrion by a proton
symporter
It then under goes oxidative decarboxylation to acetyl-CoA,
catalyzed by multienzyme complex (pyruvate dehydrogenase
complex) present in inner mitochondrial membrane
Inhibition of pyruvate metabolism leads to lactic acidosis

19. Oxidation of pyruvate to acetyl-CoA
Salient feature
• Substrate: Pyruvate
• Product: Acetyl-CoA
• Site: All Tissue
• Compartment: Mitochondria
• Nature: Catabolic

20. Oxidation of pyruvate to acetyl co-A

21. Pyruvate dehydrogenase complex
• Multienzyme complex
• Associated with inner
mitochondrial membrane
• Analogous to α-
ketoglutarate
dehydrogenase complex of
the citric acid cycle
• Require 5 coenzyme
–TPP (vitamin B1)
–CoA
–NAD
–FAD
–Lipoic acid