Carbohydrates

Carbohydrates, often referred to as hydrates of carbon, are the most abundant biomolecules on Earth and are chemically defined as polyhydroxy aldehydes or polyhydroxy ketones, or compounds that can be hydrolyzed into them. In most carbohydrates, hydrogen and oxygen are present in the same 2:1 ratio found in water. They are broadly classified based on their size and products of hydrolysis: monosaccharides are the simplest single units; oligosaccharides contain two to ten monosaccharide units joined by glycosidic linkages (with disaccharides being the most common); and polysaccharides are massive polymers containing hundreds or thousands of units, which do not taste sweet and are thus called non-sugars.

Monosaccharides are colorless, crystalline solids that dissolve easily in water but are insoluble in non-polar solvents. They typically follow the general formula CnH2nOn, with D-glucose being the most abundant in nature. They are categorized both by their functional groups and their number of carbon atoms. Aldoses contain an aldehyde group (like glyceraldehyde or glucose), while ketoses contain a ketone group (like dihydroxyacetone or fructose). Based on carbon count, they are named with the suffix -ose, such as trioses (3 carbons), tetroses (4), pentoses (5), and hexoses (6).

The three-dimensional stereochemistry of sugars is highly complex. Except for dihydroxyacetone, all monosaccharides contain one or more chiral carbon atoms, allowing them to exist as non-superimposable mirror images called enantiomers. The absolute configuration is defined by the chiral center furthest from the carbonyl carbon, using glyceraldehyde as the reference point. If the hydroxyl (-OH) group on this reference carbon is on the right in a Fischer projection, it is a D-isomer; if on the left, it is an L-isomer. Almost universally, the D-forms of monosaccharides predominate in nature, reflecting the stereospecificity of the evolutionary enzymes that synthesize them. Sugars that differ in stereochemistry at only a single chiral center are known as epimers. For instance, D-glucose and D-mannose are C-2 epimers, while D-glucose and D-galactose are C-4 epimers.

In aqueous environments, monosaccharides with five or six carbons predominantly fold into cyclic structures due to the low angle and eclipsing strain of these rings. This occurs when the carbonyl group reacts intramolecularly with a hydroxyl group, forming a hemiacetal (from an aldose) or a hemiketal (from a ketose). Six-membered sugar rings are called pyranoses (resembling pyran), while five-membered rings are called furanoses (resembling furan). Cyclization turns the former carbonyl carbon into a new chiral center known as the anomeric carbon, producing two diastereoisomers called anomers. If the hydroxyl group on the anomeric carbon is below the plane of the ring, it is the alpha-anomer; if it is above the plane, it is the beta-anomer. In solution, pure alpha or beta forms will slowly undergo mutarotation—opening and re-closing the ring until they reach a stable equilibrium mixture of both forms.

Monosaccharides can be modified into various derivatives:

• Glycosides: Formed when the hemiacetal reacts with an alcohol to produce an acetal. The anomeric hydroxyl group condenses with another compound, creating a glycoside (e.g., a glucoside or galactoside). This modification is found in antibiotics like streptomycin and active compounds like ouabain.
• Sugar Acids: Oxidation of the aldehyde group produces an aldonic acid (e.g., gluconic acid or Vitamin C); oxidation of the terminal hydroxyl produces a uronic acid (e.g., glucuronic acid); and oxidation of both ends yields an aldaric acid.
• Sugar Alcohols (Alditols): The carbonyl group is reduced to a hydroxyl group, producing linear molecules like sorbitol and xylitol that cannot cyclize.
• Amino Sugars: A hydroxyl group is replaced by an amino or acetylamino group, forming crucial structural components like glucosamine, N-acetylglucosamine (NAG), and N-acetylmuramic acid (NAM).

When two monosaccharides link together via an O-glycosidic bond, a disaccharide is formed. This bond connects the anomeric carbon of one sugar to a hydroxyl oxygen of another, locking the participating anomeric carbon’s configuration in the alpha or beta position. Important disaccharides include:

• Maltose: Two glucose molecules linked by an α-(1→4) glycosidic bond, derived from starch and glycogen.
• Lactose: Galactose and glucose linked by a β-(1→4) glycosidic bond, serving as a major animal energy source.
• Sucrose (Table Sugar): Glucose and fructose linked by an α-(1→2)-β glycosidic bond. Because the anomeric carbons of both sugars participate in the bond, sucrose has no free anomeric carbon and is classified as a non-reducing sugar. When sucrose is hydrolyzed by dilute acid or the enzyme invertase, it yields an equimolar mixture of glucose and fructose; this is called invert sugar because the optical rotation of the solution shifts from dextrorotatory to levorotatory during the process.

Sugars that maintain a free anomeric carbon (like all monosaccharides, maltose, and lactose) are capable of acting as reducing agents and are termed reducing sugars.

Polysaccharides (Glycans) provide structural support and energy storage, divided into homopolysaccharides and heteropolysaccharides. Homopolysaccharides contain only one type of monomer:

• Starch: The plant storage form of glucose. It is a mixture of linear amylose (alpha 1→4 bonds, forming a helical structure that turns deep blue with iodine) and highly branched amylopectin (branching via alpha 1→6 bonds every 25-30 residues, turning reddish-purple with iodine).
• Glycogen: The animal storage form of carbohydrate, similar to amylopectin but much more densely branched (every 8 to 10 residues).
• Cellulose: A linear, unbranched structural plant polysaccharide made of glucose joined by beta 1→4 bonds. It is the most abundant organic compound in the biosphere, though human enzymes cannot hydrolyze it.
• Chitin: The second most abundant carbohydrate, structurally identical to cellulose except the monomer is N-acetylglucosamine. It forms fungal cell walls and arthropod exoskeletons.

Heteropolysaccharides contain multiple monomer types:

• Glycosaminoglycans (GAGs): Unbranched, negatively charged chains made of repeating disaccharide units typically containing an acidic sugar (like glucuronic acid) and an amino sugar (like NAG or N-acetylgalactosamine). With the exception of hyaluronic acid, GAGs (like chondroitin sulfate, keratin sulfate, and heparin) contain sulfate groups and are covalently attached to core proteins to form proteoglycans.
• Peptidoglycan (Murein): Forms eubacterial cell walls via alternating residues of NAG and NAM linked by beta1→4 bonds, heavily cross-linked by short peptides.

Finally, carbohydrates often covalently attach to proteins to form glycoproteins, which are a type of glycoconjugate. In these complexes, the carbohydrate chain is either attached to the amide nitrogen of an asparagine side chain (an N-linkage) or to the oxygen atom in the side chain of serine or threonine (an O-linkage).