CARBOHYDRATE CHEMISTRY and MTABOLISM

1. CARBOHYDRATE CHEMISTRY and MTABOLISM By Mohamed Aly Abdelhafez, PhD Medical Biochemistry & Molecular Biology Department Faculty of Medicine, Cairo University

2. Definition • Carbohydrates Chemically, they are polyhydroxy aldehydes or ketones. • Carbohydrates have the following biological functions: • 1- Chief source of energy (50-60%) of daily requirement. • 2- Partners of cell organelles and intercellular matrix structure, in complex with protein (as glycoprotein or proteoglycans), or with lipids (as cerebrosides or gangliosides). • 4- Interconvert with some amino acids and lipid derivatives in • intermediary metabolic pathways.

3. Classification • The basic unit is monosaccharide (mono-= single or one) or simple sugar. Structurally monosaccharides contain carbon and water elements (hydrogen and oxygen). • Oligosaccharides (oligo- = few) are containing 2-10 monosaccharide units. • If more than 10 monosaccharide units it is polysaccharide(poly-= many).

4. Monosaccharides • Monosaccharides are water-soluble sweet carbohydrates. • They are classified into: a) aldoses e.g.glucose , galactose , mannose, and b) ketoses e.g. fructose. • Each class is further subclassified according to number of carbon atoms per molecule of monosaccharide into: Triose (C3) , tetrose (C4) ,pentose (C5) as ribose ,hexose (C6) as glucose ,galactose ,fructose ,as well as mannose ; and heptose (C7) . • CHO CHO CH2OH CHO CHO • HCOH HCOH C=O HCOH HCH • HOCH HOCH OHCH HCOH HCOH • HCOH HOCH HCOH HCOH HCOH • HCOH HCOH HCOH CH2OH CH2OH • CH2OH CH2OH CH2OH • Glucose Galactose FructoseRibose Deoxyribose • H E X O S E S P E N T O S E S

5. Monosaccharide derivatives • a- Deoxy-sugar, in which C-2 is devoid of oxygen, e.g. deoxyribose. • b- Sugar alcohol, in which the carbonyl group (aldehyde or ketone) are reduced into alcoholic group. • c- Amino-sugar, e.g. glucosamine. • d- Aminosugar acid, the aminosugar is linked to pyruvic or lactic acid, neuraminic acid. • e- Uronic acid, the terminal -OH group of C-6 is oxidized to –COOH,e.g. glucuronic acid. • f- Aldonic acid, the aldehyde group of C-1 is oxidized to -COOH, e.g. gluconic acid • g- Aldaric acid, both the -OH of terminal carbon and -CHO of C-1 are oxidized to -COOH, e,g. Glucaric acid.

6. Cyclic Configuration • The cyclic configuration may be in a vertical or a horizontal ring. In either condition it is 5-C ring that is closed with oxygen bridge, called pyranose. • A 4-C ring with oxygen bridge is another form called furanose. All forms are inter-changeable. • Essentially the carbonyl group should be involved in formation of oxygen bridge. It is the anomeric carbon. • As the ring is formed the anomeric carbon becomes asymmetric carbon.

7. Cyclic Configuration • According to the position of OH – group the sugar is α – or β- . • The α – sugar of vertical assigned ring, the OH- group is oriented on the right of the anomeric carbon but in horizontal ring the orientation this OH is below the plane of the ring. Vice versa for β-sugar. • Similarly all carbons involved in the ring formation; i.e., what's on the right of the straight chain is below the plane of the horizontal ring. An exception is 4th.C in furanose and 5th. C in pyranose structure because of rotation associated with ring closure.

8. Properties of monosuccharides • Optical activity: • The optically active compound contains at least one asymmetric carbon atom (the four valances are satisfied by four different atoms or groups. • The plane-polarized light (PPL) is that passed through a calcite (CaCO3) prism. The vibrations of the electromagnetic waves are unified in one plane instead of being in three perpendicular planes. • As PPL passes through an optically active material it deviates either in clock-wise direction (right-handed or dextrorotation, signed "+" ) or anti-clock-wise direction (left-handed or levorotatory, signed "-" ) . • Deviation of light path depends on the number of asymmetric carbons per molecule.

9. Optical activity • Glucose is dextrorotatory, it is called dextrose , whereas fructose is levorotatory , levulose. • Specific angle of rotation; considering the pH, concentration , temperature , and other dissolved materials in solution. • The angle of rotation value is preceded by the symbol (+) or (-) depending on the direction of rotation. The angle is measured by an instrument called Polarisoscope or Polarimeter. • D- or-L sugar depends on orientation of the -OH group in the penultimate carbon atom, assuming the aldehyde or ketonic group is oriented "up“. Right handed position of this –OH, the sugar is in D- form, whereas left-sided position it is in L- form.

10. Optical activity • D- and L- nomination does not indicate the direction of rotation of the PPL. • α- and β- are so. • Mutarotation, (change of the specific angle of rotation of a recently prepared sugar solution). Although both α- and β- are in the same direction of rotation of PPL, yet they have different values. • The D- sugar is a mirror image of the L-form of the same sugar , both are called enantiomorphs , antimers , or stereo-isomers. Both have the same specific angle of rotation but on reversed direction.

11. Optical activity • Other form of isomerism is the similarity in number and distribution of groups around the asymmetric carbon except one carbon ; e.g., glucose and galactose are aldohexoses identical in structure except the -OH attached to C-4 is on the right-side in glucose and on the left-side in galactose. Both sugars are epimers in C-4. • If an equimolar amount of the D-form and L-form of the same sugar are mixed together, they will lose their optical activity, i.e. no deviation of PPL as it passes through this mixture. The mixture of this character is called racemic mixture. Deviation of light path to either side by the D- form is corrected by the other form by the same angle but on the other side.

12. Other monosacchride properties • monosaccharides are reducing agents in alkaline media .Cupric ions of Fehling or Benedicts solutions • Monosacchrides can be oxidized into the corresponding aldonic, uronic or aldaric acids (in vitro ) depending on the strength • Glucose is oxidized to gluconic acid, glucuronic acid or to glucaric (saccharic acid). Galactose is similarly oxidized to mucic acid. • Monosaccharides are reduced to the corresponding alcohol; i.e. glucose to sorbitol. • The primary alcoholic group of C1 or terminal carbon can be esterified by phosphorylation. Glucose-6-phosphate, fructose-1-phosphate and ribulose-5-phosphate are examples.

13. Oligosaccharides • Oligosaccharides are two-monosaccharide units per molecule. The units are joined together with a glycosidic bond. • Glycosidic bond binds the carbonyl group of one molecular unit with either an alcoholic group of C-4 of the other unit (as in lactose and maltose), or with the carbonyl group of the other unit (as in sucrose). In the latter occasion the sugar loses the properties due to the free carbonyl group as reduction of metallic ions and interchange of the α- and β- forms. • Disaccharides are oligosaccharides containing two monosaccharide residues. • Lactose is the milk sugar. It is composed of glucose and galactose moles linked by β-glycosidic bond .

14. Oligosaccharides • Maltoseis barely sugar made of two moles of glucose linked by α-glucosidic bond. Sucrose is cane sugar that is made of one mole of glucose and another of fructose linked by β-glycosidic linkage. • Hydrolysis of the disaccharide to the parent monosaccharides changes the angle of rotation of PPL. In case of sucrose the change affects the angle magnitude and direction. Sucrose is dextrorotatory, on hydrolysis whether enzymatic or acidic, the hydolysate is inverted into strong levoroitatory mixture of glucose and fructose. Hence, sucrose is known as invert sugar and sucrase, the enzyme hydrlysing sucrose, is called invertase.

15. Polysaccharides • Carbohydrates containing 10 or more monosacchride units per molecule. • If the monosaccharide unit is of one-type, it is homopolysaccharide (both starchand glycogen are made of hundreds of glucose units, glucosans or glucans) . Dextrin, is similar to starch but of fewer glucosyl units, lower molecular weight and it is less branched. Cellulose is another homopolysaccharide but cannot be digested in human gastrointestinal tract (GIT) due to absence of the specific digesting enzyme (β-glucosidase). • Starch is plant in origin. It is a mixture of amylopectin (branched-chain glucosan, represents 80-90 % of starch molecule) and amylose (straight-chain glucosan represents 10–20 % of starch mole). • Acid hydrolysis of starch results in mixture of dextrins of different molecular weights, maltose and free glucose depending on the pH, temperature, and duration of hydrolysis process.

16. Polysaccarides • Glycogen is of animal origin. It is similar in structure to amylopectin but more highly branched. • Inulin is a plant fructosan that is not digested and thus unutilizable. It is present in garlic ,onion and artichoke. • Agar is sulfated galactosan present in sea-weeds. It makes gels and sols depending on the prevailing temperature and concentration. It is used in preparation of bacterial cultures in the clinical laboratory. • Pectins are sugar-acid polymers. They are present in citrus fruits, apple, carrots and beets. They make a jelly-like substance when soluble in water. They have pharmaceutical and food industrial applications. • Gum acacia and gum Arabic are homo-polysaccharides that, also have pharmaceutical and industrial uses.

17. Hetero-polysaccarides • Heteropolysaccharides are glucosaminoglycans (GAGS), or mucopolysaccharides. • complex macromolecules, repetitive units of disaccharides • A monomer consists of uronic acid(D-glucuronic acid or its C-5 epimer L-iduronic acid) and amino sugar(hexosamines as glucosamine or galactosamine). • They are either sulfate-free as hyaluronic acid (N-acetylglucosamine +glucuronic acid) or • sulfated glucosaminoglycans as: heparine , chondroitin sulfate , dermatan sulfate and heparan sulfate.

19. Acetyl CoA oxaloacetate 2 CO2 3 (NADH+H+) FADH2 Citric acid Succinate GTP GDP Succinyl CoA Intermediates Krebs’ Cycle (Tricarboxylic acid cycle,TCA)

20. Glycogen metabolism

21. Lipogenesis