Carbohydrate metabolism

1. Carbohydrate metabolism 糖 代 谢

2. Section 1 Overview

4. Carbohydrates in general are polyhydroxy aldehydes or ketones or compounds which yield these on hydrolysis.

5. Biosignificance of Carbohydrates Carbohydrates are the most abundant biomolecules on earth and have multiple roles in all forms of life. • Carbohydrates serve as energy stores (e.g., starch in plants, glycogen in animals), fuels (e.g., glucose), and metabolic intermediates (e.g., ATP, many coenzymes辅酶). • Carbohydrates serve as structural elements in cell walls of plants (cellulose) or bacteria (peptidoglycans), exoskeletons of arthropods (chitin), and extracellular matrixes of vertebrate animals (proteoglycans).

6. Carbohydrates serve as recognition signals in glycoproteins and glycolipids determining cell-cell recognition, intracellular location, and metabolic fates of proteins (thus sugars, like nucleic acids and proteins, are also information rich! But codes unknown). • Carbohydrates (ribose and deoxyribose) form part of the structural framework of RNA and DNA.

7. Cells Have Choice among Alternative Substrates, but Glucose Is more Important for Their Needs • The most important fuctions of carbohydrates • Generation of metabolic energy • Maintenance of a normal blood glucose level • Supply of specialized monosaccharides as biosynthetic precursors • Some sugar derivates are important bioactive compounds

8. Carbohydrates can be categorized into monosaccharides, oligosaccharides, and polysacchrides. • Monosacchrides单糖 are simple sugars consisting of a single polyhydroxyl aldehyde or ketone unit (e.g., glyceraldehyde, dihydroxyacetone, ribose, glucose, galactose, ribulose, and fructose). • Oligosaccharides低聚糖 contain two (disaccharides) or a few monosaccharides joined by glycosidic bonds (e.g., lactose, sucrose, maltose, some covalently linked sugars in glycoproteins and glycolipids).

9. Polysaccharides多糖 contain long chains of (hundreds to thousands) monosaccharide units joined by glycosidic bonds (e.g., glycogen, starch, cellulose, chitin, and glycosaminoglycans).

10. Monosacchrides contain one carbonyl group and two or more hydroxyl groups. Monosacchrides can be divided into two families: aldoses醛糖and ketoses酮糖. • Aldoses have their carbonyl groups at the ends of the carbon chains, thus being an aldehyde. • Ketoses have their carbonyl groups at places other than the ends, thus being ketones. • The simplest aldose is glyceraldehyde, and the simplest ketose is dihyoxyacetone, both being triose丙糖或三糖.

12. Monosacchrides containing four, five, and six carbon atoms in their backbones are called tetroses, pentoses (e.g., ribose and deoxyribose), and hexoses (e.g., glucose and fructose), respectively. • Hexoses are the most common monosacchrides in nature, including D-glucose, D-mannose, D-galactose, D-fructose.

15. Glyceraldehyde is conventionally used as the standard for defining D and L configurations: D-glyceraldehyde has the -OH group on the right, L-glyceraldehyde has the -OH group on the left.

16. For sugars with more than one asymmetric carbon atom, the D- and L- symbols refer to the absolute configuration of the asymmetric carbon farthest to the carbonyl group (e.g., in D-fructose, the -OH on C-5 has the same configuration as the asymmetric carbon in D-glyceraldehyde, therefore, D- and L- glucoses are not enantiomers but stereoisomers!)

18. The forms of monosaccharides predominate in nature, just as L-amino acids do.

20. Most of the monosaccharides found in living organisms are the D-isomers (e.g., D-ribose, D-glucose, D-galactose, D-mannose, D-fructose) • Each stereoisomer has a different conventional name, ending with “-ose” suffix. • Ketoses are often named by inserting an “ul” into the name of the corresponding aldoses (e.g., aldopentose is named as ribose, the ketopentose is named as ribulose.

25. Two sugars differing in configuration at a single asymmetric carbon is called epimers to each other (e.g., D-glucose and D-mannose are epimers at C-2; D-glucose and D-galactose are epimers at C-4).

26. An aldehyde can react with one alcohol to form a hemiacetal (two alcohol to form acetal), a ketone with an alcohol to form a hemiketal. • In the open chain form of glucose, the aldehyde group at C-1 and the hydroxyl group at C-5 react to form two six-membered pyran-like cyclic stereoisomers: the a-D-glucopyranose (the -OH group attached to C-1 locates on a different side from the C-6 atom) and the β-D-glucospyranose (-OH of C-1 on the same side of the plane as C-6), thus being specifically called anomers to each other.

27. Anomeric carbon

30. Monosaccharide units can link with each other through O-glycosidic bonds to form oligo- and polysaccharides. • Disaccharides consist of two monosaccharides linked through an O-glycosidic bond. • Sucrose, lactose and maltose are the most abundant disaccharides in nature. • In sucrose (common table sugar), the anomeric carbon of one a-D-glucose is joined to the hydroxyl oxygen atom on C-2 of an β-D-fructose.

33. Sucrose, lactose, and maltose can be abbreviated as Glc(α1-2β)Fru, (or Fru(β2-1a)Glc), Gal(β1-4)Glc, and Glc(α1-4)Glc, respectively. • Both lactose and maltose have a free anomeric carbon (not involved in glycosidic bond) that can be oxidized, thus being reducing sugars. • The end of an oligo- and polysaccharide having a free anomeric carbon is called the reducing end. • Sucrose does not have a reducing end (the anomeric carbons of both saccharide units are involved in glycosidic bond).

34. The three disaccharides can be hydrolyzed into two monosaccharide units by specific sucrase (also called invertase), lactase (β-galactosidase in bacteria), and maltase existing on the outer surface of epithelial cells lining of the small intestines. (milk allergy过敏 is due to lack of lactase in the intestines).

35. Glycogen and starch are mobilizable stores of glucose in animals and plants respectively. • Glycogen (mainly in liver and skeleton muscles) is a polymer of (a1-4) linked glucose units with (a1-6) linked branches (occurring about once every 10 glucose residues). • Starch can be linear or branched polymers of glucose, called amylose直链淀粉 and amylopectin支链淀粉, respectively. • Amylose consists of D-glucose residues in (a1-4) linkage. • Amylopectin has about one (a1-6) branch per 30 (a1-4) linkages. • Amylopectin is like glycogen except for its lower degree of branching.

36. Each amylose has one nonreducing one and one reducing one, but each amylopectin and glycogen has one reducing end and many nonreducing ends. • Starch and glycogen ingested in the diet are hydrolyzed by α-amylase (present in saliva and intestinal juice) that break the a1,4 glycosidic linkages between glucose units. (starting from the nonreducing ends). The end of an oligo- and polysaccharide having a free anomeric carbon is called the reducing end.

43. Cellulose and chitin are structural homopolysaccharides同聚多糖 with similar composition and structures. • Cellulose, like amylose, is a linear homopolysaccharide of 10,000 or 15,000 D-glucose residues, but with (β1-4) linkages. • Chitin is a linear homopolysaccharide composed of N-acetyl-D-glucosamine residues also with (β1-4) linkages. • The only chemical difference between cellulose and chitin is the replacement of a hydroxyl group at C-2 with an acetylated amino group.

44. Most animals lack enzymes to hydrolyze cellulose but some (like termites and ruminant animals) can use cellulose because of the cellulase secreted by symbiotic microorganisms. • The (β1-4) linkage allow the polysaccharide chains of cellulose and chitin to take an extended conformation forming parallel fibers through intrachain and interchain hydrogen bond.

48. Glucose Is the Principal Transported Carbohydrate in human • The most abundant monosaccharide in dietary carbohydrates is glucose. • Glucose Can be transported by blood • Glucose Cannot be stored in cells, only if it can be converted to glycogen • Blood glucose level

49. Intestinal epithelium cells SGLT Intestinalcavity of small intestine portal GLUT Various tissue cells Systemic circulation liver Glucose Uptake into the Cells Is Regulated • Glucose transporter • The glucose were absorbed by sodium-dependent glucose transporter (SGLT) • And then, they were take up by muscle, adipose tissue, brain and other tissue cells through glucose transporter(GLUT)

50. Glucose transporters (GLUT) • GLUT1~5 GLUT1: RBC GLUT4: adipose tissue, muscle