Metabolism of carbohydrate

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

4. 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

5. Aerobic glycolysis Breakdown of glucose in the cell with mitochondria in adequate supply of oxygen is called aerobic glycolysis End product: Pyruvate  A cetyl-coA  TCA cycle  CO 2 & H 2 O

6. 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

7. 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

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

9. Traits Glucokinase Hexokinase 1. Affinity for glucose Low Km value- high High Km value- low 2. Specificity Phosphorylated only glucose Non specific, c an 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

10. 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

11. 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

12. 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

13. 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

14. 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

15. Fate of Pyruvate In cytoplasm Lactate (reduction) Alanine (transamination) Glucose (gluconeogenesis) In mitochondria Acetyl coA (oxidation & decarboxylation) Oxaloacetate (carboxylation)

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

17. 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

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

19. Oxidation of pyruvate to acetyl co-A

20. 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

21. Thank You