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Carbohydrate metabolism



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  • 2. CONTENTS Introduction Classification of Carbohydrates Glycolysis Glycogenolysis Glycogenesis Citric acid cycle Pentose phosphate pathway Applied aspects Regulation of Blood glucose
  • 3. NUTRITIONNutrition is defined as “the science ofhow the body utilizes food to meetrequirements for developmentgrowth, repair and maintenance”
  • 5. IntroductionIn plants, In Animals,Carbondioxide+water Fat + protein Glucose carbohydrate(stored as starch orconverted to cellulose)
  • 6. Biomedical ImportanceGlucose is a major carbohydrateIt is a major fuel of tissuesIt is converted into other carbohydrates Glycogen for storage. Ribose in nucleic acids. Galactose in lactose of milk. They form glycoproteins & proteoglycans They are present in some lipoproteins (LDL) . Present in plasma membrane:glycocalyx. Glycophorin is a major intergral membrane glycoprotein of human erythrocytes.
  • 7. CarbohydratesMonosaccharides Polysaccharide Disaccharides Oligosaccharides
  • 8. Monosaccharides Depending on carbon Depending on aldehyde or atoms ketone group•Trioses: Glycerose-Aldo Dihydroxyacetone-Ketone •Aldoses•Tetroses Erythrose (A) Erythrulose (K) •Ketoses•Pentoses: Ribose (A) Ribulose (K)•Hexoses: Glucose (A) Fructose (K)
  • 9. •Disaccharides •Maltose •Sucrose Oligosaccharides •Maltotriose Polysaccharides •Linear - Starch •Branched- Dextrin
  • 10. METABOLISM The entire spectrum of chemical reactions, occuring in the living system are referred as “Metabolism”. Types of metabolic pathways Anabolic pathways: Protein synthesis. Catabolic Pathways: Oxidative phosphorylation. Amphibolic pathways: Citric acid cycle.
  • 11. Food molecules simpler molecules Amphibolic pathway Anabolic Catabolic 2H P Proteins, carbohydrates, CO2+H2O lipids, nucleic acids etc.
  • 12. Metabolic pathways may be studied at different levels of organisation. At tissue level At subcellular level
  • 13. Overview ofOverview ofCarbohydrateCarbohydrateMetabolismMetabolism
  • 14. Carbohydrates Serve as primary source of energy in the cell Central to all metabolic processes GlucoseCytosol - anaerobic HexokinasePentosePhosphate Glucose-6-P Glc-1- phosphateShunt glycolysis glycogen Pyruvate
  • 15. cytosol Pyruvatemitochondria(aerobic) Acetyl CoA FATTY ACIDS Krebs Reducing AMINO cycle equivalents ACIDS Oxidative Phosphorylation (ATP)
  • 17. GlycolysisDefn: It is defined as sequence of reactions of glucose to lactate & pyruvate with the production of ATP. It is derived from greek word glycose -sweet or sugar, lysis- dissolution.Site: Cytosolic fraction of cell
  • 19. STAGE II
  • 20. STAGE III
  • 21. Bioenergetics in Glycolysis:Total of 8 ATP is formed in glycolysis.Oxidation of glucose in aerobic condition:38 ATP Anaerobic condition: 2 ATP
  • 22. Biomedical importance of Glycolysis Principal route of metabolism. Production of acetyl coA in citric acid cycle. Metabolism of fructose & galactose. Provides ATP in absence of Oxygen.
  • 23. Clinical Aspects Hemolytic Anaemias: Inherited aldolase A & pyruvate kinase deficiencies. Skeletal muscle fatigue Inherited Pyruvate dehydrogenase deficiency- Lactic acidosis Fast growing cancer cells glycolysis proceeds at faster rate – increased acidic environment- implication in certain types of cancer.
  • 24. Metabolism of Glycogen Major storage form of carbohydrate. Glycogenesis: occurs in muscle & liver.
  • 25. Biomedical importance Liver glycogen largely concerned with transport & storage of hexose units. For maintenance of blood glucose mainly between meals.
  • 26. Clinical aspects Glycogen storage diseasesType of disorder Cause of disorderType I (Von Gierke’s Glucose-6-phosphatase disease) deficiency.Type II (Pompe’s disease) Acid maltase deficiency.Type III (Cori’s disease) Debranching enzyme deficiency.Type IV (Andersen’s disease) Branching enzyme deficiency.Type V (Mcardle’s disease) Muscle phosphorylase deficiency.
  • 27. Type VI (Her’s disease) Liver phosphorylase deficiency.Type VII (Tarui’s Phosphofructokinase disease) deficiency .Type VIII Liver phosphorylase kinase.
  • 29. Biomedical importance Final common pathway for oxidation of carbohydrates, lipids , & proteins. Major role in gluconeogenesis, transamination, deamination & lipogenesis. Vitamins play a key role in this cycle Eg; Riboflavin – FAD. Niacin – NAD. Thiamine. Pantothenic acid as a part of co-A.Bioenergetics :12 ATP per cycle.
  • 30. Pentose Phosphate PathwayAlternative route for metabolism of glucoseIt occurs in cytosolSequence of reactions occur in two phases1.Oxidative non reversible phase-Forms NADPH2. Non oxidative reversible phase.- Forms ribose precursors for nucleotide synthesis.
  • 31. Biomedical importance Glutathione peroxidase protects erythrocytes against hemolysis. Pentose useful in synthesis of DNA & RNA. NADPH is required for reductive biosynthesis of fatty acids & steroids. NADPH is required in synthesis of amino acids. Microsomal cytochrome P450 system brings detoxification of drugs & foreign compounds.
  • 32. Clinical aspects Erythrocyte hemolysis Impairment of generation of NADPH manifests as hemolysis when given drugs like Antimalarial- Primaquine aspirin or sulfonamides. (G6 PD) Deficiency: It makes red cells susceptible to hemolysis X linked inheritance Onset of Anaemia is rapid Mild jaundice
  • 33.  Defects in Fructose metabolism Lack of hepatic fructokinase causes Fructosuria. Absence of Hepatic aldolase-Hereditary fructose intolerance. Hypoglycemia, vomiting, sweating. Albuminuria, aminoaciduria. Reduced caries incidence. . Fructose & sorbitol in lens asssociated with diabetic cataract.
  • 34. Gluconeogenesis Synthesis of glucose from non carbohydrate compounds is called “gluconeogenesis” Site : Mainly occurs in Liver & kidney matrix in cytosol.
  • 35. Regulation of gluconeogenesis Influence of Glucagon. Availability of substrates. Alcohol inhibits gluconeogenesis.
  • 36. Proteoglycans & GlycosaminoglycansSeven glycosaminoglycans1 Hyaluronic acid2 Chondriotin sulfate3 Keratan sulfate I4 Keratan sulfate II5 Heparin6 Heparan sulfate7 Dermatan sulfate
  • 37. Mucopolysaccharidoses MPS  DefectMPS I (Hurler syndrome) Alpha-L-IduronidaseMPS II (Hunter syndrome) Iduronate sulfataseMPS IIIA (Sanfilippo A) Heparan sulfate N sulfataseMPS IIIB (Sanfilippo B) Alpha-AcetylglucosaminidaseMPS IIIC (Sanfilippo C) Acetyl transferase
  • 38.  MPS IVA (Morquio A)  Galactose-6-sulfatase MPS IVB (Morquio B)  Beta galactosidase MPS VI (Maroteaux  N acetylgalactosamine 4 Lamy syndrome) sulfatase MPS VII (Sly)  Beta glucoronidase
  • 39. Hunter’s syndrome
  • 40. Functions of glycoaminoglycans Structural components of extracellular matrix. Act as sieves in extracellular matrix. Facilitate cell migration. Corneal transparency. Anticoagulant (Heparin). Components of synaptic & other vesicles.
  • 41. GlycoproteinsOligosaccharide (glycan) covalently attached to their polypeptide backbones.Glycoprotein FunctionsCollagen Structural moleculeMucins Lubricant & protective agentTransferrin & Transport molecule.CeruloplasminImmunoglobulin molecule ImmunityAlkaline phosphatase Enzymatic activity
  • 42. Regulation of Blood glucosePostabsorptive state: Blood glucose is 4.5- 5.5mmol/L.After carbohydrate meal: 6.5-7.2mmol/LDuring fasting : 3.3-3.9mmol/L
  • 43. Blood Glucose GlycogenolysisDIET Gluconeogenesis
  • 44. Metabolic & hormonal mechanisms regulate blood glucose level Maintenance of stable levels of glucose in blood is by Liver. Extrahepatic tissues. Hormones .
  • 45. Liver Extrahepatic tissues Freely permeable to glucose  Relatively impermeable via GLUT-2 transporter. to glucose. Passage through cell membrane is rate limiting  Passage is facilitated step. through various enzymes. Glucose is phosphorylated  It has direct effect on entry by hexokinase on entry into of glucose into the cell. cell
  • 46. Role Of Insulin Role of insulin
  • 47. Regulation of blood glucose levels InsulinAnabolic in response to hyperglycemiaLiver  Stimulates glycogen synthesis, glycolysis, and fatty acid synthesisMuscle  Stimulates glycogen synthesisAdipose tissue  Stimulates lipoprotein lipase resulting in uptake of fatty acids from chylomicrons and VLDL  Stimulates glycolysis for glycerol phosphate synthesis (precursor to triglycerides)
  • 48. Role in insulin in lowering blood glucose
  • 49. Glucagon Produced by A cells of islets of langerhans of pancreas Actions opposite to Insulin. Its secretion is stimulated by hypoglycemia. It stimulates glycogenolysis & gluconeogenesis from amino acids & lactate.
  • 50. Regulation of blood glucose levels by Glucagon Catabolic, in response to hypoglycemiaLiver  Activates glycogen degradation, gluconeogenesisAdipose tissue  Stimulates lipolysis and release of fatty acids
  • 51. Role of glucagon
  • 52. Role of thyroid hormone It stimulates glycogenolysis & gluconeogenesis. Hypothyroid Hyperthyroid Fasting blood glucose is  Fasting blood glucose is lowered. elevated Patients have decreased  Patients utilise glucose ability to utilise glucose. at normal or increased Patients are less rate sensitive to insulin than normal or hyperthyroid patients.
  • 53. Glucocorticoids Glucocorticoids are antagonistic to insulin. Inhibit the utilisation of glucose in extrahepatic tissues. Increased gluconeogenesis .
  • 54. Epinephrine Secreted by adrenal medulla. It stimulates glycogenolysis in liver & muscle. It diminishes the release of insulin from pancreas.
  • 55. Other HormonesAnterior pituitary hormones Growth hormone: Elevates blood glucose level & antagonizes action of insulin. Growth hormone is stimulated by hypoglycemia (decreases glucose uptake in tissues) Chronic administration of growth hormone leads to diabetes due to B cell exhaustion.
  • 56. SEX HORMONES Estrogens cause increased liberation of insulin. Testosterone decrease blood sugar level.
  • 57. Hyperglycemia Hypoglycemia Thirst, dry mouth  Sweating Polyuria  Trembling,pounding Tiredness, fatigue heart Blurring of vision.  Anxiety, hunger Nausea, headache,  Confusion, drowsiness Hyperphagia  Speech difficulty Mood change  Incoordination.  Inability to concentrate
  • 58. Clinical aspectsGlycosuria: occurs when venous blood glucose concentration exceeds 9.5-10.0mmol/LFructose-1,6-Biphosphatase deficiency causes lactic acidosis & hypoglycemia..
  • 59. Diabetes MellitusA multi-organ catabolic response caused by insulininsufficiencyMuscle  Protein catabolism for gluconeogenesisAdipose tissue  Lipolysis for fatty acid releaseLiver  Ketogenesis from fatty acid oxidation  Gluconeogenesis from amino acids and glycerolKidney  Ketonuria and cation excretion  Renal ammoniagenesis.
  • 60. Role of carbohydrates in dental caries Fermentable carbohydrates causes loss of caries resistance. Caries process is an interplay between oral bacteria, local carbohydrates & tooth surface Bacteria + Sugars+ Teeth Organic acids Caries
  • 61. Role of carbohydrates in periodontal disease Abnormal Excessive carbohydrateglucose metabolism intake Diabetes Mellitus Obesity Periodontal disease Periodontal disease
  • 62. References Text book of Biochemistry –Harper. Satyanarayan. A C Deb. Text book of Physiology –Ganong. Text book of Oral Pathology – Shafers. Principles & practice of Medicine-Davidson. Nutrition & oral health – The Dental clinics of North America.
  • 63. Thank you