Carbohydrates

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CARBOHYDRATES Carbohydrates are the major food and energy supply of the body which come from grains, starchy vegetables, legumes, sucrose, lactose, glucose and fructose. Excess carbohydrates are converted to fats and stored as adipose tissue. The most common disease related to carbohydrate metabolism is Diabetes Mellitus, characterized by insufficient levels of active insulin. PROCESS WHICH AFFECT CARBOHYDRATE METABOLISM: Glycogenesis – the formation of glycogen from glucose. Glycogen is principally stored in the liver and some in the skeletal muscles. Glycogenolysis – the breakdown of glycogen to glucose. Glycolysis – the breakdown of glucose to lactate and pyruvate. Gluconeogenesis – the formation of glucose from other intermediate products like amino acids and fatty acids.

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B. HORMONES WHICH CONTROL GLUCOSE

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Glucagon a. Produced by the alpha cells of the pancreatic islets and raises blood glucose level by promoting glycogenolysis.

Insulin a. Produced by beta cells of pancreatic islets and lowers blood glucose level. b. Effects in CHO metabolism: b.1. facilities entry of glucose into cells b.2. promotes glycogenesis b.3 promotes lipogenesis which is the conversion of glucose to fats b.4. enhances use of glucose for intermediate energy through increased glycolysis. b.5. inhibits gluconeogenesis. b.6. decreases glycogenolysis. c. Increase administration or excess production of insulin leads to hypoglycemia. Insulin shock is defined as extreme hypoglycemia characterized by muscular spasms and loss of consciousness.

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B. HORMONES WHICH CONTROL GLUCOSE

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Cathecholamines ( EPINEPHRINE and NOREPINEPHRINE ) a. Released from chrmaffin cells of the adrenal medulla and raises sugar levels by promoting both liver and skeletal muscle glycogenolysis.

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GLUCOCORTICOIDS ( CORTISOL and CORTICOSTEROIDS ) a. Produced by the cells of the zona reticularis and zona fascilculata of the adrenal cortex and elevates blood sugar levels by protein degredation and increased gluconeogenesis.

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GROWTH HORMONE ( SOMATOTROPHIC HORMONE ) a. Produced and secreted by the somatotrophic cells of the anterior pituitary and elevates blood sugar levels by decreasing the rate of glucose utilization by the peripheral tissues.

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THYROXINE a. Secreted by the follicular cells of the thyroid and raises blood sugar levels by increasing the rate of glucose absorption in the intestines and stimulating glycogenolysis.

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Somatostatin a. Produced by the delta cells of the pancreatic islets and supresses both insulin and glucagon, HYPOTHALAMUS.

C. DIABETES MELLITUS ( DM ) CLASSIFICATION OF DM : a. Primary DM – based on the activity and state of the pancreas involving the insulin-producing cells. a.1. INSULIN DEPENDENT DM ( IDDM ) or TYPE I DM: - occurs an early age ( juvenile onset ) - seen in thin patients - abrupt onset of symptoms - ketosis prone - requires insulin treatment - congenital – not hereditary a.2. NON – INSULIN DEPENDENT DM ( NIDDM ) or TYPE II DM: - occurs after the age of 40 ( maturity onset ) - seen in obese patients - gradual onset of symptoms - a degree of basal insulin production persists - hereditary – genetically linked - requires that potentiate insulin release like oral hypoglycemic agents - ketosis resistant

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C. DIABETES MELLITUS ( DM )

b. Secondary DM – associated with other endocrinopathies b.1. Cushing’s syndrome – a disease affecting the adrenal cortex or causing excessive secretion of diabetegenic glucocorticoids. b.2. Pheocromocytoma – a tumor involving the chromocytes of the adrenal medulla causing excessive production of epinephrine and norepinephrine. b.3. Acromegaly – a disease characterized by enlargement of the bones of hands, feet and skull due to excessive amounts of growth hormones. 2. CLASSICAL TRIAD : a. POLYURIA – due to osmotic diuresis effected by glucose. In Diabetes Mellitus the urine is voluminous and at the same time concentrated. b. POLYDYPSIA – excessive thirst as a response to excessive water loss via urination. c. POLYPHAGIA – excessive apetite due to the faliure of glucose to enter the peripheral tissues.

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C. DIABETES MELLITUS ( DM ) 3. PROTEIN METABOLISM IN DM : a. There is an increased protein turnover with amino acids converted to glucose ( gluconeogenesis ) b. This results to a negative nitrogen balance, protein depletion and wasting. This explains the poor resistance to infections by the diabetics. 4. FAT METABOLISM IN DM : a. There is an increased catabolism of lipids which increases the formation of ketone bodies and decreased synthesis of fatty acids and tryglycerides.

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D. METHODS OF GLUCOSE DETERMINATION :

1. CHEMICAL METHODS : A. ALKALINE COPPER REDUCTION METHODS : PRINCIPLE: In a hot alkaline solution, cupric ions are reducted to cuprous ions by glucose with formation of cuprous oxide. Other reducing sugars are lactose, fructose and pentose. Sucrose is a non-reducing sugar. A.1. FOLIN – WU the Folin – Wu PFF is made to react with a phosphomolybdate reagent to produce a blue and product of phosphomolybdenum blue. This method lacks specificity since it measures saccharoids like glutathione, ergothione, ascorbic acid, uric acid, creatinine, and glucoronoids. This axplains the high reference value of this method, which is 80 – 120 mg/dl. A.2. NELSON – SOMOGYI This is the most accurate redox method and believed to be a measure of true glucose, because of the saccharoid free PFF. The brium sulfate formed acts as an absorbent to which saccharoids adhere. In this method, the PFF is made to react with an arsenomolybdate reagent forming a blue end product of arsenomolybdenum blue.

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D. METHODS OF GLUCOSE DETERMINATION : A.3. NEOCUPROINE PFF is made to react with dimethyl phenanthroline hydrochloride or neocuproine forming a yellow to yellow – orange cuprous – neocuproine complex. A.4. BENEDICT’S A modification of Folin – Wu method which uses a special bisulfate copper solution. A.5 SHAEFFER – HARTMANN – SOMOGYI Cuprous ion formed react with iodine in acidic solution and excess iodine in the blank and the sample is titrated with thiosulfate. The difference is equal to the reducing sugar present in the sample.

B. ALKALINE FERRIC REDUCTIONMETHOD ( HAGEDORN – JENSEN ) PRINCIPLE: In a hot alkaline solution, yellow ferricyanide ion iodizes glucose to a colorless ferrocyanide ion. Also known as inverse colorimetry of measuring glucose.

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D. METHODS OF GLUCOSE DETERMINATION : C. CONDENSATION OR ORTHO – TOLUIDINE METHOD ( GLUCONEER ) PRINCIPLE: Condensation of aldosaccharides such as glucose with various aromatic amines like o-toluidine, in a hot glacial acetic acid to produce a stable green color ( N-glucosylamine ). C.1. This is the most specific non-enzymatic method for glucose determination. The hot acidic solution is for enolization or for enol formation. C.2. Sources of error may come from an icteric serum and from a patient under a galactose load or suffring from galactosemia.

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D. METHODS OF GLUCOSE DETERMINATION :

2. ENZYMATIC METHODS: a. GLUCOSE OXIDASE METHOD a.1. SAIFFER – GERSTENFIELD PRINCIPLE: Glucose is measured by the reaction with glucose ixidase, gluconic acid and hydrogen peroxide are formed. Hydrogen peroxide then reacts with ah oxygen receptor such as ortho-toluidine or ortho-dianisidine in a reaction catalyzed by peroxodase to form blue color. Glucose

Gluconalactone

Gluconic Acid + H2O2

H2O2 + ORTHOTLUIDINE = GREEN TO BLUE END COLOR ( SCHIFF BASE )