Carbohydrates (1) PDF

Phytochemistry, PPC303  Carbohydrates 1 CARBOHYDRATES Carbohydrates are produced by plants during the process of photosynthesis. As the name implies, carbohydrates consist of carbon, hydrogen and oxygen with the last two elements usually present in the same proportion as in water...

Phytochemistry, PPC303  Carbohydrates 1 CARBOHYDRATES Carbohydrates are produced by plants during the process of photosynthesis. As the name implies, carbohydrates consist of carbon, hydrogen and oxygen with the last two elements usually present in the same proportion as in water. They may be represented by the general formula Cx(H2O)y.  On a functional group bases, carbohydrates are characterized as - Polyhydroxy aldehydes or - Polyhydroxy ketones and their derivatives.  Metabolism of Carbohydrates After absorption, the metabolism of monosaccharides proceeds according to the body's requirements. This results in: - Energy production by conversion to CO2 & water. - Storage as glycogen in the liver or as triglycerides in adipose tissue. - Conversion to keto acids, amino acids or protein.  Classification of Carbohydrates According to the number of mono-saccharide units present in the molecule: 1- Simple carbohydrates (sugars): Monosaccharides: Pentose (e.g. Xylose, Arabinose), Hexoses ((a) Aldoses: e.g. Glucose, Mannose and Galactose. (b) Ketoses: e.g. Fructose),... Disaccharides: 1) Reducing disaccharides: e.g. Lactose and Maltose. 2) Non-reducing disaccharides: e.g. Sucrose. Trisaccharides: Tetrasaccharides: 2- Polysaccharides: - Homo-polysaccharides: Containing only one type of monosaccharide units: Glucosane, Fructosane,… - Hetero-polysaccharides: Upon hydrolysis they give more than one type of monosaccharide units. 3. Mucopolysaccharides (Polysaccharides of animal origin): e.g chitin, hyaluronic acid, heparin, chondroitin sulfate. 4. Complex Carbohydrates: 1) Glycosides. 2) Glycoproteins. 3) Glycolipids.  Importance of Carbohydrates Many pharmaceutical products contain carbohydrates as;  Therapeutic agents or due to their  Pharmaceutical importance.  Mutarotation Just Reading  The interconversion between α & β - forms of sugar in solution, through the open chain structure till equilibrium is established between the α & β - forms: OH α-form H C OH β-form C OH CH2OH CH2OH H O OH H HO C O H H H OH H H C OH OH OH H OH OH C OH H OH H OH CH2OH D- Configuration of the highest numbered asymmetric carbon, D if OH is on the right and L if OH is on the left  Monosaccharides Glucose Dextrose, glucopyranose, Grape sugar: Example of aldohexoses Glucose β-D-Glucopyranose  Uses:  Used as a ready source of energy in various forms of starvation.  Osmotic diuretic (I.V., 5% solutions made with physiologic salt solution). they enter the kidney tubules and cannot be reabsorbed so cause an increase in the osmotic pressure within the tubule, causing retention of water within the lumen, and thus reduces the reabsorption of water, increasing urine output (i.e. diuresis). Used in solution (I.V) to supply fluid and to sustain the blood volume. Fructose Levulose, Fructofuranose, Fructopyranose (Fruit sugar). Fructose occurs naturally in most fruits and in honey. Fructose β-D-Fructofuranose  Uses:  Used as a food for diabetics to greater extent than glucose (used as an energy source in diabetes patients because it has a low glycemic index)  In infant feeding formulae.  Amino Sugars: Glucosamine Occurrence:  Glucosamine is naturally present in shellfish, animal bones and bone marrow.  It is also present in some fungi, such as Aspergillus niger.  Uses:  Oral glucosamine is marketed as a treatment of osteoarthritis, Since glucosamine is a precursor for glycosaminoglycans, which are major components of joint cartilage so prevent cartilage degeneration. Ultimate joint care formulae: Genuphil tab.& syrup ® Glucosamine capsules ® Some semi-synthetic glucose derivatives: (Gold thio-glucose) Aurothioglucose Uses: It is used I.M. for the treatment of rheumatic arthritis Gold derivatives of glucose Some synthetic glucose derivatives: Auranofin Thio –1- β-D-glucopyranosyl) (triethyl phosphine) gold 2,3,4,6- tetra-acetate Uses: It is orally administered for the treatment of Phosphine rheumatic arthritis (Phosphorus trihydride) Sugar alcohol:  Obtained as reduction products of the corresponding sugars: Examples: - Mannitol (Reduction of mannose). - Glucitol (Reduction of glucose). - Xylitol (Reduction of xylose).  Mannitol Occurrence: Mannitol is naturally obtained from manna (ornamental tree). Mannitol is also obtained by catalytic hydrogenation of mannose.  Uses:  Osmotic diuretic.  Diagnostic agent in kidney function test; It is not metabolized by the body and excreted unchanged (about 80% of 100 g dose appears in the urine within 3 hours). ▪ Mannitol has been used for its laxative properties.  Mannitol is used as excipient in chewable tablets.  Mannitol hexanitrate is used as a coronary vasodilator (Oral dose 30 mg daily).  Mannitol-nitrogen mustard is an antineoplastic agent (dose 50-100 mg I.V.) (Acting to prevent, inhibit or halt the development of a neoplasm (a tumor)).  Xylitol Occurrence:  It is found in the fibers of many fruits and vegetables, including various berries, corn husks and mushrooms.  Xylitol is produced by hydrogenation of xylose. Uses: Xylitol is used as a sweetener in chewing gums and pastilles. Other applications include oral hygiene products such as toothpaste, fluoride tablets and mouthwashes. Xylitol is a "tooth-friendly” sugar alcohol: Xylitol 1- This is because the structure of xylitol contains a tridentate ligand, (H-C-OH)3 that can rearrange with Ca. This interaction allows for Ca to be transported through the saliva and remineralize enamel before dental caries forms. 2- Xylitol is specific in its inhibition of the Streptococcus mutans, bacteria that commonly found in the human oral cavity and is a significant contributor to tooth decay. Sugar acids: Calcium Gluconate It is the calcium salt of Gluconic acid. Preparation: 1- Electrolytic oxidation of glucose (at C1) in the presence of calcium carbonate. 2- Ca gluconate is also prepared on a commercial scale by bacterial fermentation of a 25- 40% solution of glucose in the presence of calcium carbonate. 2 Uses: – Used as a source of soluble, non-toxic, well tolerated form of calcium, given orally, I.M. or I.V. – Calcium gluconate therapy is indicated in conditions with Ca deficiency such as:  Parathyroid deficiency.  Tetany, involuntary contraction of muscles due to low plasma calcium concentration, increases the permeability of neuronal membranes to sodium ions, causing contraction of peripheral skeletal muscles.  General Ca deficiency in women & children.  Ferrous Gluconate Uses: 2  Ferrous gluconate is classified as hematinic (increase the amount of hemoglobin in the blood) and is employed orally or by injection in iron deficiency anemia.  It causes less gastric distress than other ferrous salts.  Glucuronic acid Occurrence:  It occurs naturally as a component of many gums, mucillages, hemicelluloses. Preparation :  It is obtained by selective enzymatic oxidation of glucose (at C 6). CHO CHO H C OH H C OH HO C H HO C H Glucose Enzyme H C Glucuronic acid OH H C OH H C OH H C OH CH2OH COOH Uses: Relief of certain arthritic conditions, as it is an important component of cartilage, nerve sheath, joint capsule tendon, joint fluid and intercellular cement substances.  Disaccharides A) Reducing Disaccharides: Lactose (Milk sugar) Occurrence:  Lactose is a by- product obtained of whey, which is the portion of milk that is left after the fat and casein (cheese protein) have been removed for the production of butter and cheese. Upon the evaporation of whey, lactose crystallize out.  4 1 4-O (β-D-galactopyranosyl ) D- glucopyranose Uses: - Diluent in tablets and powders. - Nutrient in infants’ formulae, being more easily digested than sucrose.  Semisynthetic disaccharide Lactulose 1 4 4-O-(β-D galactpyranosyl) D-fructofuranose Source: Lactulose is a semisynthetic sugar prepared by alkaline rearrangement of lactose (glucose fructose).  Uses:  Treatment of chronic constipation (laxative); Orally ingested lactulose reaches the colon unchanged. Bacteria in the colon metabolize lactulose to acetic acid and lactic acid. The osmotic pressure of lactic acid leads to the increase in the fecal bulk and this stimulates the peristaltic movement & enhance evacuation. Duphalac syrup ® Sedalac ® Laxolac ®  The most significant therapeutic use of this sugar is to decrease the blood ammonia concentration in portal-systemic encephalopathy (A neuropsychiatric disorder that occurs secondary to chronic liver disease). The acidified stools trap ammonia thus reabsorption of the ammonium ion is prevented, and blood ammonia levels may be decreased by 25 to 50%. B) Non- Reducing Disaccharides: Sucrose (Cane sugar, Beet sugar) 2-O-(α-D-glucopyranosyl) β-D-fructofuranose Occurrence: - Sugar cane. - Sugar beet. Uses:  Preparation of syrups.  Sweetening agent in pharmaceutical products.  In sufficient concentration in an aqueous solution (66% w/v) is bacteriostatic and preservative. Semisynthetic Sucrose derivatives: Sucralfate - Sucralfate is the basic aluminum salt of the fully sulfated derivative of sucrose.  Uses: Treatment of peptic and duodenal ulcer. *The most frequent adverse effect is constipation. Mechanism of action: Sucralfate forms a large complex with proteins that adheres to the ulcer, thus building a barrier that prevents penetration of gastric acids, pepsin (an enzyme released by the stomach and that degrades food proteins) and bile acid and allow healing. In addition, sucralfate suspension adsorbs bile acids and pepsin, diminishing their concentration in the stomach.