Biomedically Glucose Is The Most Important Monosaccharide

The Structure of Glucose Can Be Represented in Three Ways

The straight-chain structural formula (aldohexose; Figure 13—1A) can account for some of the properties of glucose, but a cyclic structure is favored on thermo-dynamic grounds and accounts for the remainder of its chemical properties. For most purposes, the structural formula is represented as a simple ring in perspective as proposed by Haworth (Figure 13-1B). In this representation, the molecule is viewed from the side and above the plane of the ring. By convention, the bonds nearest to the viewer are bold and thickened. The six-mem-bered ring containing one oxygen atom is in the form of a chair (Figure 13-1C).

Sugars Exhibit Various Forms of Isomerism

Glucose, with four asymmetric carbon atoms, can form 16 isomers. The more important types of isomerism found with glucose are as follows.

(1) D and L isomerism: The designation of a sugar isomer as the D form or of its mirror image as the L form

Table 13-1. Classification of important sugars.

Aldoses

Ketoses

Trioses (C3H6O3) Tetroses (C4H8O4) Pentoses (C5H10O5) Hexoses

Glycerose Erythrose Ribose Glucose

Dihydroxyacetone Erythrulose Ribulose Fructose

6CH2OH

HOCH2

HO OH

HOCH2

H OH

HO-4

Figure 13-1. D-Glucose. A: straight chain form. B: a-D-glucose; Haworth projection. C: a-D-glucose; chair form.

Figure 13-1. D-Glucose. A: straight chain form. B: a-D-glucose; Haworth projection. C: a-D-glucose; chair form.

Pyran

Furan

Furan

HOCH2

a-D-Glucopyranose

HOCH 2

H OH

H OH a-D-Glucofuranose

Figure 13-3. Pyranose and furanose forms of glucose.

HO-2C-H

L-Glycerose (L-glyceraldehyde)

CH2OH

D-Glycerose (D-glyceraldehyde)

HOCH2

HO H HO OH

OH H a-D-Fructopyranose

HO H HO

ß-D-Fructopyranose

HO 2C H

H 3C OH

D-Glucose

Figure 13-2. d- and L-isomerism of glycerose and glucose.

HOCH2

HOCH2

LhJ M3

OH H

a-D-Fructofuranose

HOCH2

4HH3CoH

OH H H2 ß-D-Fructofuranose

Figure 13-4. Pyranose and furanose forms of fructose.

3CH2OH

Alpha Glycerose

is determined by its spatial relationship to the parent compound of the carbohydrates, the three-carbon sugar glycerose (glyceraldehyde). The L and D forms of this sugar, and of glucose, are shown in Figure 13-2. The orientation of the —H and — OH groups around the carbon atom adjacent to the terminal primary alcohol carbon (carbon 5 in glucose) determines whether the sugar belongs to the Dor L series. When the —OH group on this carbon is on the right (as seen in Figure 13-2), the sugar is the D-isomer; when it is on the left, it is the L-isomer. Most of the monosaccharides occurring in mammals are D sugars, and the enzymes responsible for their metabolism are specific for this configuration. In solution, glucose is dextrorotatory— hence the alternative name dextrose, often used in clinical practice.

The presence of asymmetric carbon atoms also confers optical activity on the compound. When a beam of plane-polarized light is passed through a solution of an optical isomer, it will be rotated either to the right, dextrorotatory (+); or to the left, levorotatory (—). The direction of rotation is independent of the stereochemistry of the sugar, so it may be designated D(—), d(+), l(—), or l(+). For example, the naturally occurring form of fructose is the D(—) isomer.

(2) Pyranose and furanose ring structures: The stable ring structures of monosaccharides are similar to the ring structures of either pyran (a six-membered ring) or furan (a five-membered ring) (Figures 13-3 and 13-4). For glucose in solution, more than 99% is in the pyranose form.

(3) Alpha and beta anomers: The ring structure of an aldose is a hemiacetal, since it is formed by combination of an aldehyde and an alcohol group. Similarly, the ring structure of a ketose is a hemiketal. Crystalline glucose is a-D-glucopyranose. The cyclic structure is retained in solution, but isomerism occurs about position 1, the carbonyl or anomeric carbon atom, to give a mixture of a-glucopyranose (38%) and P-glucopyra-nose (62%). Less than 0.3% is represented by a and P anomers of glucofuranose.

(4) Epimers: Isomers differing as a result of variations in configuration of the — OH and —H on carbon atoms 2, 3, and 4 of glucose are known as epimers. Biologically, the most important epimers of glucose are mannose and galactose, formed by epimerization at carbons 2 and 4, respectively (Figure 13—5).

(5) Aldose-ketose isomerism: Fructose has the same molecular formula as glucose but differs in its structural formula, since there is a potential keto group in position 2, the anomeric carbon of fructose (Figures 13-4 and 13-7), whereas there is a potential aldehyde group in position 1, the anomeric carbon of glucose (Figures 13-2 and 13-6).

Many Monosaccharides Are Physiologically Important

Derivatives of trioses, tetroses, and pentoses and of a seven-carbon sugar (sedoheptulose) are formed as metabolic intermediates in glycolysis and the pentose phosphate pathway. Pentoses are important in nucleotides,

CHO I

CH2OH D-Glycerose

CHO I

CHO I

CHO CHO

CH2OH

(D-glyceraldehyde) D-Erythrose ch2oh

D-Lyxose ch2oh

D-Xylose

CHO CHO

CH2OH D-Arabinose ch2oh

D-Ribose ch2oh

D-Galactose

Figure 13-6. Examples of aldoses of physiologic significance.

CHO I

CH2OH D-Mannose

CH2OH D-Glucose

Table 13-2. Pentoses of physiologic importance.

Sugar

Where Found

Biochemical Importance

Clinical Significance

D-Ribose

Nucleic acids.

Structural elements of nucleic acids and coenzymes, eg, ATP, NAD, NADP, flavo-proteins. Ribose phosphates are intermediates in pentose phosphate pathway.

D-Ribulose

Formed in metabolic processes.

Ribulose phosphate is an intermediate in pentose phosphate pathway.

D-Arabinose

Gum arabic. Plum and cherry gums.

Constituent of glycoproteins.

D-Xylose

Wood gums, proteoglycans, glycosaminoglycans.

Constituent of glycoproteins.

D-Lyxose

Heart muscle.

A constituent of a lyxoflavin isolated from human heart muscle.

L-Xylulose

Intermediate in uronic acid pathway.

Found in urine in essential pentosuria.

nucleic acids, and several coenzymes (Table 13-2). Glucose, galactose, fructose, and mannose are physiologically the most important hexoses (Table 13-3). The biochemically important aldoses are shown in Figure 13-6, and important ketoses in Figure 13-7.

In addition, carboxylic acid derivatives of glucose are important, including D-glucuronate (for glucuronide formation and in glycosaminoglycans) and its metabolic derivative, L-iduronate (in glycosaminoglycans) (Figure 13-8) and L-gulonate (an intermediate in the uronic acid pathway; see Figure 20-4).

Sugars Form Glycosides With Other Compounds & With Each Other

Glycosides are formed by condensation between the hy-droxyl group of the anomeric carbon of a monosaccharide, or monosaccharide residue, and a second compound that may—or may not (in the case of an aglycone)—be another monosaccharide. If the second group is a hy-droxyl, the O-glycosidic bond is an acetal link because it results from a reaction between a hemiacetal group (formed from an aldehyde and an — OH group) and an

Table 13-3. Hexoses of physiologic importance.

Sugar

Source

Importance

Clinical Significance

D-Glucose

Fruit juices. Hydrolysis of starch, cane sugar, maltose, and lactose.

The "sugar" of the body. The sugar carried by the blood, and the principal one used by the tissues.

Present in the urine (glycosuria) in diabetes mellitus owing to raised blood glucose (hyper-glycemia).

D-Fructose

Fruit juices. Honey. Hydrolysis of cane sugar and of inulin (from the Jerusalem artichoke).

Can be changed to glucose in the liver and so used in the body.

Hereditary fructose intolerance leads to fructose accumulation and hypoglycemia.

D-Galactose

Hydrolysis of lactose.

Can be changed to glucose in the liver and metabolized. Synthesized in the mammary gland to make the lactose of milk. A constituent of glycolipids and glycoproteins.

Failure to metabolize leads to galactosemia and cataract.

D-Mannose

Hydrolysis of plant mannans and gums.

A constituent of many glycoproteins.

ch2oh I

ch2oh

ch2oh

c = o

ho — c — h

c = o

I

ch2oh

ho — c — h

h — c — oh

h — c — oh

h — c — oh

c = o

h — c — oh

h — c — oh

h — c — oh

h — c — oh

ch2oh

ch2oh

ch2oh

ch2oh

ch2oh

Dihydroxyacetone

D-Xylulose

D-Ribulose

D-Fructose

D-Sedoheptulose

Figure 13-7. Examples of ketoses of physiologic significance.

other —OH group. If the hemiacetal portion is glucose, the resulting compound is a glucoside; if galactose, a galactoside; and so on. If the second group is an amine, an N-glycosidic bond is formed, eg, between adenine and ribose in nucleotides such as ATP (Figure 10-4).

Glycosides are widely distributed in nature; the agly-cone may be methanol, glycerol, a sterol, a phenol, or a base such as adenine. The glycosides that are important in medicine because of their action on the heart (cardiac glycosides) all contain steroids as the aglycone. These include derivatives of digitalis and strophanthus such as ouabain, an inhibitor of the Na+-K+ ATPase of cell membranes. Other glycosides include antibiotics such as streptomycin.

Deoxy Sugars Lack an Oxygen Atom

Deoxy sugars are those in which a hydroxyl group has been replaced by hydrogen. An example is deoxyribose (Figure 13-9) in DNA. The deoxy sugar L-fucose (Figure 13-15) occurs in glycoproteins; 2-deoxyglucose is used experimentally as an inhibitor of glucose metabolism.

Amino Sugars (Hexosamines) Are Components of Glycoproteins, Gangliosides, & Glycosaminoglycans

The amino sugars include D-glucosamine, a constituent of hyaluronic acid (Figure 13-10), D-galactosamine (chondrosamine), a constituent of chondroitin; and D-mannosamine. Several antibiotics (eg, erythromycin) contain amino sugars believed to be important for their antibiotic activity.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

Get My Free Ebook


Post a comment