Lecture 5: Metabolism of Other Hexoses and Blood Glucose PDF

Metabolism of other Hexoses and Blood Glucose Medical Biochemistry and Molecular Biology Department Faculty of Medicine – Menoufia University  A. Fructose metabolism Sources of fructose:- Sucrase 1. Sucrose...

Metabolism of other Hexoses and Blood Glucose Medical Biochemistry and Molecular Biology Department Faculty of Medicine – Menoufia University  A. Fructose metabolism Sources of fructose:- Sucrase 1. Sucrose glucose + fructose 2. Diet (honey, fruits and vegetables) Importance of fructose:- 15% of the total body energy is derived from fructose The only source of energy for spermatozoa 1. Fructose metabolism in the liver, kidney and intestine:- – These tissues contain fructokinase enzyme which converts fructose into fructose- 1-P. – Fructose-1-P is then, hydrolyzed by aldolase B enzyme to give dihydroxyacetone phosphate and glyceraldhyde.  Fructose ATP Fructokinase ADP Fructose-1-P Aldolase-B Dihydroxyacetone-P Glyceraldhyde ATP Triokinase Glyceraldhyde-3-P Aldolase-A Fructose 1,6 biphosphate Gluconeogenesis Glucose  Glyceraldehyde by triokinase gives glyceraldhyde-3-P. Glyceraldhyde-3-P is then 1. Enters glycolysis to give energy. 2. Combine with dihydroxyacetone phosphate to give glucose. 2. Fructose metabolism in muscles and adipose tissues:- – These tissues contain no fructokinase but contain hexokinase. Fructose ATP Hexokinase ADP Fructose-6-P ATP Phosphofructokinase-1 ADP Fructose 1,6 biphosphate Glycolysis 2 Pyruvate + energy 3. In the testis, lens, peripheral nerves and renal glomeruli:- Glucose is converted into fructose as follow. Sorbitol Aldolase reductase Dehydrogenase Glucose Sorbitol Fructose NADPH+H+ NADP+ NAD+ NADH+H+ N.B. In diabetes mellitus:- – Excess glucose is converted into sorbitol in the lens causing cataract.  B. Galactose metabolism Sources of galactose:- – Dietary milk: - Lactose Glucose + Galactose Importance of galactose:- Galactose enters in the structure of - Lactose - Glycolipids - Glycoproteins - Proteoglycans  1. Conversion of galactose to glucose in the liver Galactose ATP mg2+ Galactokinase ADP Galactose-1-P UDP-glucose Glucose Galactose-1-P uridyl transferase Glucose-6-Phosphatase UDP-galactose Glucose-1-P Glucose-6-P UDP-galactose 4-epimerase Phosphoglucomutase G. Synthase G. Phosphorylase UDP-glucose Glycogen Glucose-1-P  2. Conversion of glucose into galactose in mammary gland Hexokinase Phosphoglucomutase Glucose Glucose-6-P Glucose-1-P ATP mg2+ ADP UTP UDP-glucose pyrophosphorylase PPi UDP-glucose UDP-galactose 4-epimerase Lactose synthase UDP-Galactose Lactose + Glucose  Blood glucose Normal blood glucose:- – Fasting blood glucose (FBG) = 70 - 110 mg/dl. – 2 hours post prandial i.e after meal (2 hrs PP) = up to 140 mg/dl. Sources of blood glucose:- 1. Dietary carbohydrates as glucose, galactose and fructose (galactose and fructose are converted into glucose in the liver) 2. Gluconeogenic substances e,g amino acids, lactate, glycerol..etc. 3. Liver glycogen by glycogenolysis.  Variations in blood glucose 1. Hypoglycemia Definition: - Is a condition in which plasma glucose is decreased below 60 mg/dl. Symptoms:- – There is faintness, dizziness or lethargy, which may progress to coma. – If untreated → death occurs as a result of permanent cerebral damage.  Causes of hypoglycemia There are 2 types of hypoglycemia 1) Stimulative hypoglycemia:- there must be a stimulus for hypoglycemia, the stimulus may be 1. Drugs: - Insulin overdoses or poisons e.g chloroform. 2. Inborn errors of metabolism: - Galactosemia and Hereditary fructose intolerance. 3. Post gastrectomy: - This causes rapid absorption of glucose with excessive insulin secretion → hypoglycemia. 4. Excess intake of alcohol. 5. Essential reactive hypoglycemia: - it means exaggeration of the normal insulin response to carbohydrate ingestion. 6. Idiopathic hypoglycemia. 2) Fasting hypoglycemia:- There is failure to maintain normal blood glucose especially during fasting due to: 1. Starvation and malnutrition: - d.t. exhaustion of liver glycogen. 2. Inborn errors of metabolism: - these include  Dicarboxylic aciduria, maple syrup urine disease and tyrosinemia give neonatal or childhood hypoglycemia 3. Pancreatic disease: - As insulinoma, hyperinsulinism of childhood, pancreatitis and pancreatic tumors leading to enhanced glucose utilization caused by overproduction of insulin. 4. Defective glucose production due to:- – Endocrine disease:- adrenocortical insufficiency, hypothyroidism and growth hormone deficiency. – Liver disease:- sever liver cirrhosis, hepatic tumors. – Renal disease:- defective gluconeogenesis.  Glucosuria Definition: - It is the presence of glucose in urine in amounts detectable by ordinary methods. Glucosuria occurs when the venous blood glucose concentration exceeds the renal threshold for glucose (180 mg/dl). Causes:- 1. Diabetes mellitus: - due to hyperglycemia caused by lack of insulin. 2. Renal glucosuria:- it is due to low renal threshold i.e decreased renal threshold below 180 mg/dl so glucose appear in urine even at low blood glucose concentration. Caused by 1) Inherited defects in the kidney. 2) Nephritis and nephrosis. 3) Drugs e.g phlorizin which inhibits glucose reabsorption by the renal tubules. 4) Pregnancy: - There is impaired glucose tolerance and hyperglycemia. Glucosuria in pregnancy is due to low renal threshold and increased glomerular filtration rate. 5) Fanconi's syndrome: - there is defective renal tubular reabsorption of glucose, amino acids and phosphate.