BIOCHEMISTRY: A TEXTBOOK FOR UNIVERSITIES - E. S. Severin - 2004

CHAPTER 7. CARBOHYDRATE METABOLISM

CARBOHYDRATES are essential components of living organisms, which, alongside Proteins, Lipids, and Nucleic Acids, determine the Specificity of their Structure and function. They encompass a diverse group of compounds with varied and often vastly different Functions. Carbohydrates participate in numerous metabolic processes, but first and foremost, they serve as the primary source of energy. They account for approximately 75% of the daily human diet by mass and over 50% of the required daily caloric intake. However, it is a mistake to reduce the function of carbohydrates solely to providing energy for vital bodily processes. Their structural role is also noteworthy. For instance, in the form of glycosaminoglycans, carbohydrates are constituents of the Extracellular matrix. A vast number of proteins (Enzymes, transport proteins, receptor proteins, and Hormones) are Glycoproteins, where the carbohydrate moiety enhances their specificity. For example, variations in The structure of oligosaccharide fragments in the erythrocyte Cell membrane determine Blood group specificity. During METABOLISM, A large number of Organic compounds are formed from carbohydrates, serving as initial substrates for the synthesis of lipids, Amino Acids, and NUCLEOTIDES. Carbohydrate derivatives, such as glucuronides, are involved in the detoxification of xenobiotics and the inactivation of endogenous substances. Carbohydrates can also be synthesized within the Organism from other metabolites, such as Certain amino acids, glycerol, and lactic acid. While carbohydrates cannot be strictly considered essential dietary components, their complete exclusion from the diet can lead to hypoglycemia, which the body compensates for by breaking down proteins and lipids. Thus, carbohydrates are mandatory dietary components because, beyond their primary energy function (serving as cellular fuel), they participate in numerous metabolic processes within The Cell.

I. Structure of Carbohydrates

The term "carbohydrates," coined in the 19th century, was based on the assumption that all carbohydrates consist of two components—carbon and Water—and their elemental composition could be expressed by the general formula C_m(H₂O)_n. Although there are exceptions to this rule and it is not absolute, this definition still offers the simplest way to characterize the Class of carbohydrates as a whole. Furthermore, an attempt by the Commission on Chemical Nomenclature to replace the term "carbohydrates" with "glycides" was unsuccessful. The new term failed to gain widespread acceptance, whereas "carbohydrates" became firmly established and universally recognized.

Based on the number of monomer units they contain, carbohydrates can be divided into three main groups: Monosaccharides, Oligosaccharides, and Polysaccharides.

A. Monosaccharides

Monosaccharides are derivatives of polyhydric alcohols containing a carbonyl group. Depending on THE POSITION OF the carbonyl group within the molecule, monosaccharides are classified as aldoses or ketoses.

Aldoses contain a functional aldehyde group -HC = O, whereas ketoses contain a ketone group > C = O. The name of a monosaccharide depends on the number of carbon atoms it contains, for example, aldotrioses, ketotrioses, aldohexoses, ketohexoses, etc.

In terms of structure, monosaccharides are classified as simple carbohydrates because they do not undergo Hydrolysis during Digestion, unlike complex carbohydrates, which break down into simple sugars upon hydrolysis. The STRUCTURE OF THE principal monosaccharides is shown in Fig. 7-1.

Fig. 7-1. Major monosaccharides.

Human food (fruits, honey, juices) contains small amounts of monosaccharides, primarily glucose and fructose.

Glucose is an aldohexose. It can exist in both open-chain (linear) and cyclic forms. The thermodynamically favored cyclic form dictates The chemical properties of glucose. Like all hexoses, glucose possesses four asymmetric carbon atoms, which give rise to stereoisomers. Theoretically, 16 stereoisomers can be formed, the most important of which are D- and L-glucose. These types of isomers are mirror images of each other (Fig. 7-2).

Fig. 7-2. D- and L-isomers of glucose.

The orientation of the H and OH groups relative to the fifth carbon atom determines whether glucose belongs to the D- or L-series. In mammalian organisms, monosaccharides occur in the D-configuration because the enzymes catalyzing their transformations are specific to this form of glucose. When the cyclic form of a monosaccharide is established in solution, two additional isomers (α- and β-isomers) are formed, known as anomers, which represent specific Conformations of the H and OH groups relative to C₁ (Fig. 7-3). In α-D-glucose, the OH group is located below the plane of the ring, whereas in β-D-glucose, it is located above the plane of the ring.

Fig. 7-3. α- and β-anomers of D-glucose.

Fructose is a ketohexose (its keto group is located at the second carbon atom). Much like glucose, fructose exists in a cyclic form, forming α- and β-anomers (Fig. 7-4).

Fig. 7-4. α- and β-anomers of D-fructose.

B. Reactions of Monosaccharides

The presence of hydroxyl, aldehyde, and ketone groups enables monosaccharides to undergo reactions characteristic of alcohols, aldehydes, or ketones. These reactions are quite numerous. This section will describe only a subset of them, focusing primarily on those of the greatest biological significance.

In this section, the Main reactions of monosaccharides are examined using D-glucose as an example (Fig. 7-5), although it should be noted that other MONOSACCHARIDES AND THEIR derivatives also participate in Carbohydrate Metabolism.

Fig. 7-5. Monosaccharide reactions.

Mutarotation, or anomerization, is the interconversion of the α- and β-anomeric forms of monosaccharides, which exist in an aqueous solution in a state of equilibrium. Mutarotation occurs upon reaching this equilibrium through the opening and closing of the pyranose ring, which alters the spatial arrangement of the H and OH groups at the anomeric carbon of the monosaccharide.

Glycoside formation. The glycosidic bond is of critical biological importance as it is responsible for the covalent linkage of monosaccharides in oligo- and polysaccharides. During glycosidic bond formation, the anomeric OH group of one monosaccharide reacts with the OH group of another monosaccharide or an alcohol. This reaction involves the elimination of a water molecule and The formation of an O-glycosidic bond. All linear oligomers (except Disaccharides) and polymers consist of monomeric residues involved in two glycosidic bonds, with the exception of terminal residues, which form only a single glycosidic bond. Certain glycosidic residues can form three glycosidic bonds, a characteristic feature of branched oligo- and polysaccharides. Oligo- and polysaccharides may possess a terminal monosaccharide residue with a free, unreacted anomeric OH group. In this case, ring opening can yield a free carbonyl group capable of oxidation. Such oligo- and polysaccharides exhibit reducing properties and are therefore referred to as reducing sugars (Fig. 7-6).

Fig. 7-6. Structure of a polysaccharide. A. Formation of α-1,4- and α-1,6-glycosidic bonds. B. Structure of a linear polysaccharide: 1 — α-1,4-glycosidic bonds between monomers; 2 — non-reducing end (formation of a free carbonyl group at the anomeric carbon is impossible); 3 — reducing end (ring opening with the formation of a free carbonyl group at the anomeric carbon is possible).

The anomeric OH group of a monosaccharide can also react with the NH₂ group of Other Compounds, leading to the formation of an N-glycosidic bond. Such bonds are found in nucleotides and glycoproteins (Fig. 7-7).

Fig. 7-7. Formation of O- and N-glycosidic bonds in glycoproteins. 1 — N-glycosidic bond between the amide group of asparagine and the OH group of the monosaccharide; 2 — O-glycosidic bond between the OH group of Serine and the OH group of the monosaccharide.

Esterification. This is the reaction in which an ester bond is formed between the OH groups of monosaccharides and various acids. Phosphoesters—esters of monosaccharides and phosphoric acid—play a vital role in carbohydrate metabolism. Glucose 6-phosphate occupies a particularly prominent place in glucose metabolism. The formation of glucose 6-phosphate occurs via an ATP-dependent reaction mediated by Kinases. In this reaction, ATP serves as the phosphate group donor. Monosaccharide phosphoesters can also be formed without the involvement of ATP; for instance, glucose 1-phosphate is produced from Glycogen in the presence of H₃PO₄. The physiological significance of monosaccharide phosphoesters lies in the fact that they represent metabolically active structures. The phosphorylation of monosaccharides is also crucial for metabolism because cell membranes are largely impermeable to these compounds, meaning the cell retains monosaccharides specifically by keeping them in a phosphorylated state.

Oxidation and reduction. The oxidation of the Terminal Groups of glucose, -CHO and -CH₂OH, yields three distinct derivatives. Oxidation of the -CHO group produces gluconic acid. When the terminal -CH₂OH group is oxidized, glucuronic acid is formed. If both terminal groups undergo oxidation, saccharic acid (containing two carboxyl groups) is produced. Reduction of the first carbon atom results in the Formation of the sugar alcohol sorbitol.

B. Oligosaccharides

Oligosaccharides contain several (from two to ten) monosaccharide residues linked by glycosidic bonds. Disaccharides are the most common oligomeric carbohydrates found in a free form, i.e., not bound to other compounds. Chemically, disaccharides are Glycosides that contain two monosaccharides joined by a glycosidic bond in either the α- or β-configuration. Dietary disaccharides mainly include sucrose, lactose, and maltose (Fig. 7-8).

Fig. 7-8. Dietary disaccharides.

Sucrose is a disaccharide composed of α-D-glucose and β-D-fructose linked by an α,β-1,2-glycosidic bond. In sucrose, both anomeric hydroxyl groups of the glucose and fructose residues are involved in forming the glycosidic bond. Consequently, sucrose is a non-reducing sugar. Sucrose is a sweet-tasting, soluble disaccharide. Plants serve as the source of sucrose, particularly sugar beets and sugar cane, which explains its common name, "cane sugar."

Lactose, or milk sugar, is the principal disaccharide found in mammalian milk. Cow's milk contains up to 5% lactose, while human milk contains up to 8%. In lactose, the anomeric OH group of the first carbon atom of the D-galactose residue is linked by a β-glycosidic bond to the fourth carbon atom of D-glucose (a β-1,4 linkage). Since the anomeric carbon atom of the glucose residue is not involved in the glycosidic bond formation, lactose is a reducing sugar.

Maltose is ingested through foods containing partially hydrolyzed starch, such as malt and beer. Maltose is also produced during The breakdown of starch in the intestine. It consists of two D-glucose residues joined by an α-1,4-glycosidic bond.

Isomaltose is an intermediate product formed during the intestinal breakdown of starch. It consists of two D-glucose residues, but these monosaccharides are connected by an α-1,6-glycosidic bond.

G. Polysaccharides

Structural differences among polysaccharides are determined by:

✵ the structure of the monosaccharides making up the chain;

✵ the type of glycosidic bonds linking the monomers in the chain;

✵ The sequence of monosaccharide residues in the chain.

Depending on the structure of their monosaccharide residues, polysaccharides can be divided into Homopolysaccharides (all monomers are identical) and Heteropolysaccharides (monomers are different). Both types of polysaccharides can have either a linear or branched arrangement of monomers.

Depending on their functions, polysaccharides can be divided into 3 main groups:

✵ Reserve Polysaccharides, which perform an energetic function. These polysaccharides serve as a source of glucose, utilized by the organism as needed. The reserve function of these carbohydrates is ensured by their polymeric nature. Polysaccharides are less soluble than monosaccharides; consequently, they do not affect osmotic pressure and therefore can accumulate within the cell—for instance, starch in PLANT Cells AND glycogen in animal cells;

✵ structural polysaccharides, which provide mechanical strength to cells and Organs (see Section 15);

✵ polysaccharides that are Components of the extracellular matrix, participating in tissue formation as well as in cell proliferation and differentiation. Extracellular matrix polysaccharides are water-soluble and highly hydrated (see Section 15).

Human diets mainly contain polysaccharides of plant origin, such as starch and Cellulose. Glycogen, an animal polysaccharide, is ingested in smaller amounts.

Starch — the most important carbohydrate component of the human diet. It is a plant reserve polysaccharide found in the greatest amounts (up to 45% of dry weight) in cereal grains (wheat, corn, rice, etc.), as well as in plant bulbs, stems, and tubers (approximately 65% in potatoes). Starch is a branched polysaccharide consisting of glucose residues (a homoglycan). It occurs in plant cells as granules and is practically insoluble in water.

Starch consists of amylose and amylopectin (Fig. 7-9). Amylose is an unbranched polysaccharide comprising 200 — 300 glucose residues linked by α-1,4-glycosidic bonds. Due to the α-configuration of the glucose residue, the polysaccharide chain adopts a helical conformation. The blue color produced upon adding iodine to a starch solution is due to the presence of this helix. Amylopectin has a branched structure. At the branch points, glucose residues are joined by α-1,6-glycosidic bonds. The linear segments contain approximately 20 — 25 glucose residues. This forms a tree-like structure containing only one anomeric OH group. Starch is a high-molecular-weight compound comprising hundreds of thousands of glucose residues, with a molecular mass on the order of 10⁵ — 10⁸ Da.

Fig. 7-9. Structure of starch.

Cellulose (dietary fiber) — the primary structural polysaccharide of plants. It is the most abundant organic compound on Earth, accounting for 40 — 50% of Plant Cell Walls. Cellulose has a molecular mass on the order of 10⁶ Da, and its molecules can reach a length of 6 — 8 µm.

Cellulose — a linear homoglycan polysaccharide built from glucose residues interconnected by β-1,4-glycosidic bonds. The human Digestive System lacks enzymes capable of hydrolyzing the β-bonds in polysaccharides. Therefore, cellulose is a non-nutritive carbohydrate, yet this dietary component is essential for normal digestive processes.

Glycogen — a polysaccharide found in animals and humans. Much like starch in plants, glycogen performs a reserve function in animal cells; however, because foods contain only small amounts of glycogen, it has no significant nutritional value.

Glycogen is a structural analog of starch, but it has a higher degree of branching: roughly one α-1,6-glycosidic bond occurs for every 10 glucose residues.