Carbohydrate Metabolism PDF

Carbohydrate Metabolism  Digestion of Carbohydrate Salivary amylase Digestion starts in the mouth. Act on cooked starch and glycogen converting them into dextrin, maltose, iso maltose and some starch remain undigested. Pancreatic amylase Act at pH 7.1 Act on cooked and uncooked...

Carbohydrate Metabolism  Digestion of Carbohydrate Salivary amylase Digestion starts in the mouth. Act on cooked starch and glycogen converting them into dextrin, maltose, iso maltose and some starch remain undigested. Pancreatic amylase Act at pH 7.1 Act on cooked and uncooked starch converting it into maltose and iso maltose.  Final digestion by intestinal enzyme Lactose lactase glucose + galactose Maltose maltase 2 α glucose Sucrose sucrase glucose + Fructose Isomaltose dexstrinase 2 α glucose (bond between carbon 1, 6)  Digestion of cellulose Cellulose not digested due to absence of enzyme cellulase that attack β linkage. Used in treatment of constipation  Fate of Absorbed Sugar 1- Uptake by tissues Uptake by liver where galactose & fructose converted to glucose 2- Utilization by tissues A- Oxidation 1-Major pathway : glycolysis & Krebs’ cycle for production of energy 2-HMP (hexose mono phosphate) shunt: give ribose , NADP 3-Production of glucouronic acid has role in heparin synthesis B- Storage Glycogen : by glycogenesis Fat : lipogenesis C- Conversion Ribose and deoxyribose DNA and RNA Lactose milk  Glucose oxidation  All carbohydrate cycles occur in cytoplasm except Krebs’ occurs in mitochondria  Complete oxidation of glucose to CO2 + H2O occur part in cytoplasm (glycolysis) and part in mitochondria (Krebs) major pathway  Anaerobic glycolysis occurs if mitochondria is absent as in RBCs or where there is O2 lack as during muscular exercise  Glycolysis (Anarobic phase of glucose oxidation ) Embden –Meyerohf pathway Means oxidation of glucose into pyruvate Site: Cytoplasm of all tissues but more important in Muscle during exercise due to O2 lack RBCs due to absence of mitochondria Function of glycolysis 1- Energy production: It is the only sources of energy to the muscle during contraction and to RBCs due to absence of mitochondria It give 8 or 6 ATP in presence of O2. 2- Give 2,3 bishosphoglycerate (BPG) which decrease affinity of Hb to O2, so O2 go easy to tissues. 3- It gives pyruvic acid that can begin Krebs’ cycle. 4- DHAP (dihydroxy acetone phosphate) can converted to glycerol-3 -phosphate which important for lipogenesis. 5- Gives 2 amino acids: Serine derived from 3 phsphoglycerate. Alanine derived from pyruvate.  Mitochondrial pathway for glucose oxidation Complete oxidation of glucose to CO2 + H2O occur part in cytoplasm (glycolysis) and part in mitochondria (Krebs) major pathway First stage: Oxidative decarboxylation of pyruvate to acetyl CoA Second stage: Krebs cycle Ex. For Oxidative decarboxylation 1. Conversion of pyruvate to acetyl CoA (active acetate) 2. Conversion of α ketoglutarate to succinyl CoA (active succinate) Oxidative decarboxylation of pyruvate to acetyl CoA Catalyzed by different enzyme called pyruvate dehydrogenase complex (PDC) or (PDH) This requires 5 coenzymes TPP (thiamin pyrophosphate) coenzyme of Vitamin B1 Lipoic acid : 2 forms present reduced and oxidized CoASH: coenzyme of pantothenic acid FAD: coenzyme of Vitamin B2 (riboflavin) NAD: coenzyme of Vitamin B3 (Niacin) CH3-CO-COOH PDC CH3-CO~ScoA Pyruvate Acetyl-CoA NAD TPP NADH2+ CO2 +CoASH Lipoic FAD  Citric acid cycle (CAC), Krebs cycle or Tricarboxylic acid cycle (TCA) Site: Mitochondria Function of Krebs (Amphibolic role: means anabolic and catabolic) 1- Catabolic role  Production of energy 12 ATP for each acetyl-coA.  Krebs used for complete oxidation of carbohydrate, lipid, protein. 2- Anabolic role  Synthesis of heme : by succinyl CoA + glycine  Amino acids synthesis by transamination: Glutamate GPT α-ketoglutarate Aspartate GOT oxaloacetate 3- Synthesis of Fatty Acid Mitochondria Cytoplasm Acetyl CoA + oxaloacetate Citrate Citrate Acetyl CoA + oxaloacetate Synthesis of Fatty Acid 4- Gluconeogenesis Gluconeogenesis is synthesis of glucose from non carbohydrate source require Krebs cycle 5- Importance of CO2 1- Pyruvate + CO2 Oxaloacetate 2- Acetyl CoA+ CO2 Malonyl CoA (Synthesis of fatty acid) 3- NH3 + CO2 Carbamoyl phosphate (Synthesis of urea)  Hexose Monophosphate Shunt (HMP shunt) Pentose Shunt Site: occur in cytoplasm of liver Function of HMP shunt: 1-Production of pentoses Pentoses are important in synthesis of DNA , RNA 2-Production of NADPH+H which important in 1-Synthesis of fatty acid, cholesterol. 2-Synthesis of sphingosine, galactolipid. 3-Synthesis of glucouronic acid. 4-Synthesis of non essential AA. 5-Reduction of glutathione.  Favism Definition Its deficiency in glucose-6-P dehydrogenase (G6PD) lead to hemolysis of RBCs especially after intake of fava beans Mechanism G-6-P G6PD 6 Phosphogluconolactone NADP NADPH+H Oxidized glutathione Reductase Reduced glutathione NADPH+H NADP Reduced glutathione + H2O2 Peroxidase 2H2O + Oxidized glutathione So ↓ G6PD ↓ NADPH2 ↓ Reduced glutathione ↑ H2O2 ↑ Hemolysis in RBCs Blood Glucose Fasting blood glucose level 70 – 110 mg/ dl One hour after meal reach 120 – 150 mg/ dl Factors regulate blood glucose:  Hormonal Regulation I) Insulin: secreted from β cell of pancreas It ↓ blood glucose by the following: 1. Transfer glucose into cell 2. Stimulation of glycolysis through activation of hexokinase, PFK1, pyruvate kinase 3. Stimulation of glycogenesis 4. Inhibition of glycogenolysis 5. Inhibition of gluconeogenesis 6. Stimulation of lipogenesis 7. Stimulation of protein synthesis II- Anti-Insulin Hormones a) Glucagon Secreted from α cell of pancreas ↑ blood glucose by Stimulation of glycogenolysis & gluconeogenesis b) Catecholamine (epinephrine and nor epinephrine) 1. Stimulation of glycogenolysis 2. Inhibit glucose uptake by liver c) Corticosteroid (glucocorticoid) i. Stimulation of gluconeogenesis ii. Inhibit glucose uptake by tissue d) Growth hormone Inhibit glucose uptake, ↓ insulin hormone e) Thyroid hormone ↓ Insulin hormone, Stimulation of glycogenolysis  Hepatic Regulation During Fasting: Glycogenolysis & Gluconeogenesis After Meal: Glycogenesis & Lipogenesis  RenalRegulation Renal Threshold: It’s blood glucose above which (180 mg/dl) glucose appear in urine Abnormal Low Renal Threshold (100 mg/dl) called Diabetes Innocence Glucose appears in urine even insulin is normal due to kidney disease, occurs in 25% in pregnancy. Abnormal High Renal Threshold (220 mg/dl) Glucose not appear in urine even the patient is diabetic. Occur in old person. Variation In Blood Glucose Hyperglycemia ↑ blood glucose above normal Fasting: more than 126 mg/ dl 1 H after meal: more than 200 mg/ dl Cause  ↓ Insulin as in 1- Diabetes mellitus. 2- Surgical removal of pancreas ↑ Anti Insulin hormone A-Adrenaline: Stress, emotion B-Cortisone: as drug C-Thyroid: Hyperthyroidism D-Growth hormone : Gigantism  Hypoglycemia ↓ Blood glucose below 40 mg/ dl Its more dangerous than hyperglycemia because brain depend on glucose Symptoms 1. Confusion , dizziness 2. Tremors , weakness, tachycardia 3. If not managed lead to coma Causes  ↑ Insulin as in 1. Excessive dose of insulin during treatment of DM. 2. Missed meal during treatment with insulin. 3. Insulinoma is a tumor in pancreas that secretes excess insulin.  ↓ Anti Insulin hormone 1. Glucocorticoid as in Addison syndrome. 2. Pituitary hormone as in hypothyroidism. 3. Glycogen storage disease as Von Jerkes disease. 4. Fructosemia & Galactosemia.  Diabetes Mellitus Definition: Its hyperglycemia and glucosuria Type I Type II Other name Insulin dependant Non insulin diabetes mellitus dependant diabetes mellitus Age During childhood After 35 years Nutritional state Usually under weight Usually obese Hereditary state Autoimmune Moderate Plasma insulin Low or absent May be normal Oral drug Has no effect Effective TTT with insulin Always necessary May not required Complication More common Less common (ketosis ) Manifestation of Diabetes Mellitus: Carbohydrate Metabolism A- ↓ insulin ↓ glucose uptake by cell ↓ glucose in cell Polyphagia (excessive eating) B- Hyperglycemia due to ↓ glucose oxidation and ↑ gluconeogenesis ↑ blood osmolarity which take water from tissue dehydration Polydepsia (excessive drink) C- Glucosuria due to hyperglycemia excess glucose in urine osmotic diuresis Polyurea (excessive micturition) D- Excessive loss of water soluble vitamins. Protein Metabolism A- ↓ Insulin ↑protein catabolism ↑Bl. Glucose B- ↑ Protein catabolism from muscle Muscle Wasting C- ↓ Antibody formation ↓Resistance & ↑ Infection D- Poor Healing of Wound Lipid Metabolism A- ↓ insulin ↑ lipolysis in adipose tissues lead to: Loss of weight. Storage of fat in the liver: Fatty Liver B- ↑ Free Fatty acid Hypercholestrolemia and Atherosclerosis Microangiopathy: means degeneration of small blood vessels A- Retinopathy affect retina Blindness B- Nephropathy affect kidney Renal Failure Most frequent symptoms of diabetes 1- Polyphagia 2- Polyurea 3- Polydepsia  Difference between hypo and hyperglycemic coma Hyperglycemic Hypoglycemic coma coma Odour Acetone odour in No odour nose Dehydration Present (dry skin, Absent sunken eye) Pulse Normal Rabid & Weak History DM Injection of insulin TTT Inj. of insulin & K Inj. of glucose  Diagnosis of D.M Normal Impaired DM Fasting ‹ 110 110 - 125 › 126 1 H after meal ‹ 140 › 140 -200 › 200 1. Glucose Tolerance Curve Oral glucose tolerance test (OGTT) Glucose tolerance is the ability of body to utilize glucose without appearance of glucose in urine How the curve is done? The patient come fasting 12 H. The fasting blood sugar measured and urine tested for glucose. Then patient taken 50 – 100 gm glucose (1gm/kg). Then blood sugar is taken every ½ h for 2 or 3 h and the urine tested.  Normal glucose tolerance test - Fasting level 70 – 110 mg / dl After 1 H blood glucose rises to reach 180 renal threshold 120 – 150 mg/dl due to glucose absorption After 2 H blood glucose return to fasting 150 Level due to utilization of glucose by insulin Urine sample contain no glucose 70 70 0 1h 2h Curve of diabetes mellitus Fasting blood sugar severe In moderate 160 mg/ dl moderate In severe 190 mg/ dl 190 B- After 1 H renal threshold In moderate