BIOCHEMISTRY - Textbook - Ostapchenko L. I. - 2012

Chapter 11. STRUCTURE AND PROPERTIES OF CARBOHYDRATES

11.1. Monosaccharides

Monosaccharides (simple sugars, monoses) are white, crystalline, hygroscopic, sweet-tasting substances that are highly soluble in Water. Their solutions are neutral in reaction, optically active, and capable of mutarotation.

Based on the number of carbon atoms in the molecule, monosaccharides are classified into trioses, tetroses, pentoses, hexoses, heptoses, etc. Chemically, monosaccharides are polyhydroxy aldehydes or polyhydroxy ketones. Depending on THE POSITION OF the oxo group, monoses are referred to as aldoses or ketoses:

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Monosaccharides exhibit optical stereoisomerism due to the presence of asymmetric carbon atoms in their molecules (an asymmetric atom, or chiral center, is a carbon atom whose four valencies are bonded to four different atoms or groups). The number of optical isomers of a monose is 2^п (where n is the number of chiral centers in the sugar molecule). The simplest monosaccharide, glyceraldehyde, contains one asymmetric carbon atom and therefore can exist as two stereoisomers: D-glyceraldehyde and L-glyceraldehyde. The letters D and L designate the absolute configuration of the atoms around the asymmetric carbon:

The D- and L-stereoisomers of glyceraldehyde serve as configurational standards used to determine the relative configuration of other monoses by comparing the tetrahedral configuration of the penultimate carbon atom of the monosaccharide molecule with one or the other stereoisomer of glyceraldehyde.

Most naturally occurring monosaccharides possess the D-configuration and are essentially diastereomers—that is, stereoisomers that differ in the configuration of the tetrahedra of one or more asymmetric carbon atoms. They form the D-series of sugars, whose members can be viewed as derivatives of D-glyceraldehyde containing its asymmetric carbon atom. This represents the last chiral center in the carbon chain of D-series monosaccharide molecules.

Each aldose and ketose of the D-series corresponds to an L-series stereoisomer, which is the mirror image of the respective D-form. Such "mirror-image" stereoisomers are called enantiomers.

Monosaccharide stereoisomers that differ in the configuration of the tetrahedron at only one of the asymmetric carbon atoms are called epimers:

Monosaccharides exist in two molecular forms: acyclic (linear) and cyclic (hemiacetal):

The cyclic form is generated via an intramolecular reaction between the carbonyl and hydroxyl groups. In this process, the hydrogen atom of the hydroxyl group approaches the carbonyl oxygen, forming a ring through the linkage of the carbonyl carbon and the hydroxyl oxygen. This creates a new chiral center and a new hydroxyl group at the carbon atom that was previously part of the carbonyl group.

The most stable hemiacetals are formed involving the hydroxyl groups at the fourth and fifth carbon atoms of the sugar molecule. Consequently, these rings can be either five- or six-membered.

The five-membered ring of monosaccharides is called a γ-oxide ring and structurally corresponds to the heterocyclic compound tetrahydrofuran:

The six-membered ring of monoses is called a δ-oxide ring and corresponds to The Structure of tetrahydropyran:

Following the proposal of W. N. Haworth, monoses with a γ-oxide ring are termed furanoses, and those with a δ-oxide ring are termed pyranoses. The cyclic forms of monosaccharides are depicted in a way that clearly shows the spatial arrangement of hydrogen atoms and hydroxyl groups relative to the plane of the ring. According to Haworth, the rings are positioned such that the ring oxygen atoms are located furthest from the observer, while the carbon-carbon bonds closest to the observer are represented by bold lines:

Substituents at the carbon atoms that appear on the left in B. Tollens' formulas are positioned above the ring, whereas those on the right are located below the plane of the ring. In Haworth projection formulas, the sixth carbon atom in the carbon chain of a D-stereoisomer monose (Tollens' formulas) lies above the plane of the ring, whereas for the L-stereoisomer, it lies below the ring. The unusual positioning of hydrogen at C5 in these formulas is due to the spatial orientation of the C5 hydroxyl group, which becomes favorable for ring formation after the fifth tetrahedron rotates around the C4-C5 bond.

The position of the hydroxyl group relative to the anomeric carbon (C1) formed during cyclization determines whether the sugar is an α- or β-anomer. The simultaneous presence of α- and β-anomers of monoses in both furanose and pyranose forms is a manifestation of ring-chain Tautomerism:

Tautomeric forms of Monoses exist in a state of dynamic equilibrium and, depending on conditions, mutarotate from one tautomeric form into another.

At equilibrium in neutral aqueous solutions of D-glucose at 20 °C, pyranoses predominate: about 64 % β-D-glucopyranose and 36 % a-D-glucopyranose. In an aqueous solution of D-fructose under these conditions, the share of β-D-fructofuranose is 76.4 %, and that of a-D-fructofuranose is 19.5 %.

According to structural studies of hexose molecules, pyranose rings can exist in the form of eight conformational isomers (configurations) with different energy levels — two chair and six boat forms:

Natural saccharides are typically characterized by two most energetically favorable chair configurations of pyranose rings, which are usually depicted as spatial projection formulas:

When designating chair conformers according to Reeves' nomenclature, the number of the carbon atom located above the ring plane is placed as a superscript before the letter C (from chair), and the number of the carbon atom located below the ring plane is placed as a subscript after the letter.

This method of depicting monosaccharide molecules as conformational isomers allows for a better understanding of the reactivity of hydroxyl groups. For instance, pyranose hydroxyls located in the equatorial (e) plane of the formula are more reactive than those in the axial (a) position.

The hydroxyl at the anomeric carbon atom is more reactive compared to other hydroxyl groups. This hemiacetal (glycosidic) hydroxyl readily reacts with alcohols to form ethers (acetals) called Glycosides:

Depending on which anomer reacted with the alcohol, the resulting glycoside is called an a- or β-glycoside.

In the molecules of glycosides — which are Monosaccharide Derivatives in which the hydrogen atom of the hemiacetal hydroxyl is replaced by an alkyl or another radical — the substituent is called the aglycone. Depending on the atom connecting the aglycone to the monose residue, glycosides are classified into O-, N-, and S-glycosides. Among the most common O- and N-glycosides in nature (plant pigments, Flavonoids, Alkaloids, etc.), β-forms predominate, such as adenosine, which is formed in the reaction between D-ribose and adenine:

The chemical properties of monosaccharides are determined by the presence of glycosidic and alcoholic hydroxyls. The glycosidic hydroxyl is capable of interacting with the hydroxyl groups of other monoses to form a glycosidic bond, which is involved in building the molecules of oligo- and Polysaccharides:

Methylating Reagents replace the hydrogen atoms in all hydroxyl groups of monoses with methyl radicals:

In addition to ether formation, alcoholic hydroxyls participate in acylation reactions:

Both the hemiacetal hydroxyl and the primary alcoholic hydroxyl of aldoses can be easily oxidized to carboxyl groups. Oxidation of the aldehyde group with weak oxidizing agents (copper hydroxide, bromine water) yields monobasic aldonic acids. Stronger oxidizing agents (concentrated nitric acid) oxidize both the aldehyde and the primary alcohol groups to form dibasic hydroxy acids known as aldaric acids. With prior Protection of the aldehyde group, oxidation of only the primary alcohol group is possible, yielding alduronic acids:

Reduction of the aldehyde group yields the corresponding polyhydric alcohols — alditols:

Thiohemiacetals are also formed with the participation of the anomeric carbon atom:

The oxo groups of monosaccharides react with hydroxylamine to form oximes that are soluble in water and alcohols:

The interaction of monosaccharides with phenylhydrazine leads to The formation of osazones, which crystallize as yellow crystals. This reaction is used for the isolation and identification of monoses, since both aldoses and ketoses yield the same product, namely an osazone.

In a reaction with benzaldehyde, osazones are converted into ozones:

In a mildly acidic medium, the aldehyde group of ozones is reduced to a primary alcohol group, thereby completing the transition from aldoses through osazones and ozones to ketoses:

In a mildly alkaline medium, monosaccharides undergo epimeric transformations driven by the enolization of monoses:

In an acidic medium in the presence of mineral acids, an intramolecular dehydration reaction of monoses takes place, leading to the formation of furfural and 5-hydroxymethylfurfural. These compounds are capable of condensing with various phenols to form characteristic colored products, which serves as the basis for numerous identification reactions for monoses.

Biologically important monosaccharides. Although hexoses such as glucose, fructose, and galactose make up the vast majority of naturally occurring monoses, other monosaccharides also play vital roles in metabolic processes either as structural units within oligo- and polysaccharides or as independent active substances.

Trioses (СзНбОз). Two important trioses, D-glyceraldehyde-3-phosphate and dihydroxyacetone phosphate, function in the Cells of microorganisms, plants, and animals as intermediates in carbohydrate and Lipid METABOLISM:

Tetroses (С4ШО4). An important tetrose is D-erythrose-4-phosphate, which is generated in the Reactions of the Pentose Phosphate Pathway of Carbohydrate Catabolism:

Pentoses (С5Н10О5). Naturally occurring pentoses include aldoses such as D-xylose, D-ribose, and L-arabinose, as well as ketoses such as D-ribulose and D-xylulose.

D(+)-Xylose can exist in both furanose and pyranose forms as a component of plant polysaccharides known as pentosans (Xylan), most commonly in the form of β-(+)-xylopyranose:

As part of xylan, it is found in straw, wood, seed husks, and other plant Materials. Xylose is readily soluble in water, undergoes mutarotation between its forms, and is an optically active compound with a specific rotation angle at tautomeric dynamic equilibrium of +18°. Xylose can be oxidized to xylonic and trihydroxyglutaric acids, and upon reduction, it yields the pentahydric alcohol xylitol:

Xylose is used in the food industry as a sweetener, while its derivative, trihydroxyglutaric acid, serves as a substitute for citric acid.

D(+)-Ribose can exist in both cyclic and acyclic forms, but In aqueous solutions, it occurs predominantly as D-ribofuranose:

The specific rotation angle of its aqueous solution is [a]D° = 23,7^o. D-ribose is an essential component of NUCLEOTIDES, Coenzymes, and Nucleic Acids. It can be formed from D-glucose via its oxidation in The pentose phosphate pathway. The oxidation of ribose yields monobasic ribonic acid, while its reduction produces the pentahydric alcohol ribitol.

D(+)-Deoxyribose, much like D-ribose, is a building block of nucleotides and nucleic acids (DNA). It can exist in both acyclic and cyclic (furanose) forms:

L(+)-Arabinose is quite widespread in nature, occurring as a component of glycosides, Oligosaccharides, and polysaccharides (such as pectin, hemicellulose, gum arabic, and arabinans) in both pyranose and furanose forms:

Arabinose can be oxidized to monobasic arabonic acid and reduced to yield the polyhydric alcohol arabitol.

The ketopentoses D(+)-xylulose and D(+)-ribulose, in the form of their phosphate derivatives, are known as intermediate metabolites of the pentose phosphate pathway of glucose oxidation (see Chapter 12, Section 12.1.4).

Hexoses (C₆H₁₂O₆) are the most common monosaccharides found in free and bound states within PLANT AND ANIMAL Tissues, as well as serving as monomers in natural oligo- and polysaccharides. These include aldohexoses such as glucose, mannose, and galactose, and the ketohexose fructose:

The aldohexoses differ from one another only in the configurations at carbon atoms 2 and 4: glucose and mannose are C-2 epimers, whereas glucose and galactose are C-4 epimers. The ketohexose fructose differs from the other hexoses in the position of its anomeric carbon atom.

All hexoses are sweet-tasting, crystalline substances that are readily soluble in water, crystallizing from solutions as mono- and hemihydrates. They are sparingly soluble in methanol, ethanol, and pyridine, and poorly soluble or insoluble in ether and Hydrocarbons.

α-D(+)-Glucose (dextrose, grape sugar) is chemically an aldohexose that can exist in both acyclic and cyclic forms. Glucose is highly soluble in water and soluble in pyridine, methanol, and ethanol.

It crystallizes from solutions as a monohydrate, with a specific rotation angle of [α]_D²⁰ = 52,5^o. Glucose is the most widespread monosaccharide in nature, found in a free state in large quantities in seeds, flowers, fruits, and leaves of plants. It is a component of animal Body Fluids (Blood, lymph) and serves as a monomer in the molecules of oligo- and polysaccharides, primarily sucrose, lactose, starch, Glycogen, and Cellulose. Starch and cellulose serve as the natural raw materials from which glucose is obtained via enzymatic and acid Hydrolysis. This is precisely how crystalline hydrated (M = 198) and anhydrous (M = 18°) glucose is produced for use in the food and pharmaceutical industries, particularly in the synthesis of ascorbic acid.

D(-)-Fructose (levulose, fruit sugar) belongs to the ketohexoses. In its free state, fructose is found in fruits and bee honey (up to 45%). It is the sweetest of all sugars, being 2.5 times sweeter than glucose. Fructose is a monomeric component of oligosaccharides such as sucrose, raffinose, and kestose, as well as the polysaccharide inulin.

In animal cells, it is present primarily in the form of phosphate esters—fructose-6-phosphate and fructose-1,6-diphosphate—which are intermediate metabolites of Glucose Catabolism.

Fructose is readily soluble in water; the specific rotation angle of its solution is -92.5°. It crystallizes as a hemihydrate (C₆H₁₂O₆)₂·H₂O, with a melting point of 102.5–103.5 °C. In industry, fructose is obtained by the hydrolysis of sucrose or inulin and is utilized in the food industry and in diabetic dietary products.

D(+)-Galactose (cerebrose) belongs to the aldohexoses.

In a state of equilibrium between the acyclic and anomeric forms, the specific rotation of its aqueous solution is [α]_D²⁰ = 81°.

Anhydrous α-D(+)-galactopyranose has a melting point of 169 °C. In nature, it occurs both in a free state and as a component of oligosaccharides (raffinose, melibiose, stachyose) and polysaccharides (Agar-agar, galactans, gum arabic, etc.). In animal tissues, galactose is found within the molecules of the oligosaccharide lactose and its derivatives, Glycoproteins, and cerebrosides. It is used in the microbiological and confectionery industries and is obtained through the hydrolysis of lactose or galactans.

D(+)-Mannose is an aldohexose. In aqueous solutions, in a state of dynamic equilibrium between the acyclic form and the α- and β-anomers, it has a specific rotation angle of +14.5°.

Free mannose is found in barley and orange peel and is a component of plant polysaccharides known as Mannans. Mannose has also been detected in animal biological fluids, including blood, saliva, mucus, and synovial fluid. It is produced either through the isomerization of glucose or the hydrolysis of mannans.

Monosaccharide derivatives. Alongside simple monosaccharides, various derivatives of monoses—such as amino sugars, sugar acids, and sialic acids—play a vital role in the metabolic processes of living organisms.

Amino sugars. These monosaccharide derivatives are formed when a hydroxyl group on one of the carbon atoms is replaced by an amino group.

Widely distributed in nature are the 2-aminoaldohexoses: D-glucosamine, D-galactosamine, and D-mannosamine, which typically occur in plant and animal tissues as their N-acetyl derivatives—N-acetyl-α-D-glucosamine, N-acetyl-α-D-galactosamine, and N-acetyl-α-D-mannosamine:

N-acetyl derivatives of amino sugars are key Structural components of Chitin (the primary polysaccharide forming the exoskeleton of insects, Mollusks, and crustaceans), Blood Plasma polysaccharides, glycoproteins, chondroitin sulfates, and certain Sphingolipids.

Along with N-acetyl derivatives, N-methylated and phosphorylated amino sugar derivatives also occur naturally. In animal organisms, amino sugars and their derivatives perform specialized Functions as constituents of the vitreous humor, synovial fluid, mucous secretions, and other biological substances.

Sugar acids are formed through the oxidation of the aldehyde group, the hydroxymethyl group, or both of these groups simultaneously within an aldose molecule.

These include aldonic, alduronic, and aldaric acids:

The oxidation of D-glucose yields D-gluconic, D-glucuronic, and D-glucaric acids. These are strong acids that form soluble, neutral salts. Glucuronic acid is the most widespread in nature; it occurs in a free state and is a component of blood glycoproteins, Connective Tissue polysaccharides, xylans, and plant Gums.

In the Human and Animal body, free glucuronic acid plays a crucial role in the detoxification and elimination of various toxic substances—including xenobiotics and metabolic end-products—by converting them into glucuronide conjugates. This occurs through the formation of glycosidic bonds (with phenols or Steroids) or ester bonds (with bilirubin). Galacturonic acid, the oxidation product of galactose, is present in pectic substances, plant tissues, and certain microbial polysaccharides.

Sugar acids can form internal esters, or lactones, featuring five- or six-membered rings. For instance, the aerobic oxidation of glucose mediated by glucose oxidase from the mold Penicillium notatum leads to the formation of δ-gluconolactone:

This specific oxidation reaction of D-glucose forms The basis of the glucose oxidase method for the Quantitative determination of glucose in solutions.

Sialic acids are acyl derivatives of 3,5-dideoxy-5-aminononulosonic acid (neuraminic acid). Neuraminic acid can be viewed as a Condensation product of D-mannosamine and Pyruvate. Several N- and O-acyl as well as glycolyl derivatives of this acid are known, which are formed by attaching an acetyl or glycolyl group to the amino or hydroxyl groups of neuraminic acid:

Sialic acids serve as structural components of glycoproteins and Glycolipids in the Plasma Membranes of animal cells. As part of gangliosides, they also play a key role in the functioning of The Nervous system.