Biochemistry: Carbohydrates and Their Functions

Carbohydrates are essential for various biological functions: providing and storing energy, recognizing molecules, protecting cells, signaling, binding cells, lubricating, controlling protein movement, and maintaining structure.

A monosaccharide is a simple sugar molecule that cannot be further broken down by hydrolysis. It is the basic building block of complex carbohydrates.

A disaccharide is a carbohydrate formed by the union of two monosaccharides by a glycosidic linkage. Examples include maltose and sucrose.

A polysaccharide is a complex carbohydrate composed of many monosaccharide units linked together by glycosidic bonds. Examples include starch, glycogen, and cellulose.

An aldose is a monosaccharide containing an aldehyde group. It has a carbonyl group at the end of the carbon chain.

A ketose is a monosaccharide containing a ketone group. It has a carbonyl group within the carbon chain.

Enantiomers are stereoisomers that are mirror images of each other and are nonsuperimposable. They differ in the spatial arrangement of atoms around a chiral center.

D-enantiomers are the most important naturally occurring saccharides. They are assigned based on the configuration of the chiral carbon farthest from the carbonyl group.

Two molecules are mirror images and cannot be superimposed on one another.

A system that assigns absolute stereochemical configuration based on a set of rules. Groups are ranked by priority (SH>OR>OH>NH2>CO2H...).

Isomers differing in orientation about one or more chiral carbons, but not mirror images.

In molecules with more than one chiral carbon, this prefix refers to the configuration of the carbon farthest from the carbonyl group.

The carbon derived from the carbonyl group in open chain form. It's the site of anomeric configuration in cyclic forms.

Two cyclic forms of monosaccharides (alpha & beta) that differ in the orientation of the hydroxyl group at the anomeric carbon.

Cyclic forms of monosaccharides (five-membered rings) are called furanose. An example is Ribose in RNA.

Cyclic forms of monosaccharides (six-membered rings) are called pyranose, an example is glucose.

A bond formed between two monosaccharides, resulting in the elimination of a water molecule.

Sucrose is a common disaccharide composed of glucose and fructose, linked by a glycosidic bond between the carbon 1 of glucose and the carbon 2 of fructose.

Maltose is a disaccharide composed of two glucose molecules linked by an alpha-1,4 glycosidic bond.

Lactose is a disaccharide composed of galactose and glucose, linked by a beta-1,4 glycosidic bond.

Amylose is a linear polysaccharide composed of many glucose molecules linked by alpha-1,4 glycosidic bonds.

Amylopectin is a branched polysaccharide composed of many glucose molecules linked by alpha-1,4 and alpha-1,6 glycosidic bonds.

Glycogen is a branched polysaccharide composed of many glucose molecules linked by alpha-1,4 and alpha-1,6 glycosidic bonds. It's the primary way that animals (and fungi) store glucose, and it's mainly found in the liver and muscles.

Two monosaccharides differing in configuration around only one chiral carbon

A cyclic ester formed by reaction between the carboxyl group at C1 and the hydroxyl group at C5 of an aldonic acid

A derivative of a sugar where the carbonyl group is reduced to a hydroxyl group

An isomer where the configuration differs due to bond rotation, not breaking/forming bonds

A sugar molecule with an aldehyde group at the end of the carbon chain

A sugar with a phosphate group attached, important in energy metabolism

A derivative of a sugar where the carbonyl group at C6 is oxidized

An organic compound formed by reacting the anomeric hydroxyl of a cyclic monosaccharide with the hydroxyl group of another compound

Amylopectin is a branched polymer of glucose, similar to glycogen but with less frequent and shorter branches. It is a major component of starches, serving as an energy storage molecule in plants.

Amylose is a linear polymer of glucose units linked by (α1→4) glycosidic bonds. Its helical structure creates a large interior core that stores glucose. This structure makes it ideal for energy storage.

Cellulose is a linear polymer of glucose units linked by (β1→4) glycosidic bonds. Its rigid, planar structure provides structural support in plant cell walls.

Chitin, a structural polysaccharide found in the exoskeletons of arthropods and the cell walls of fungi, is similar to cellulose but with a nitrogen-containing group attached to each glucose unit.

Glycosaminoglycans (GAGs) are complex, highly charged polysaccharides composed of repeating disaccharide units. They act as structural components in connective tissues and play a role in various biological processes.

Heparin is a highly sulfated GAG that acts as a natural anticoagulant. It binds to antithrombin III, inhibiting blood clotting enzymes.

Peptidoglycans are complex polysaccharides cross-linked with short peptides, providing structural support to bacterial cell walls.

Gram-positive bacteria have a thick layer of peptidoglycan in their cell walls, while Gram-negative bacteria have a thin layer of peptidoglycan and an outer lipid membrane.

The process of converting glucose-6-phosphate to UDP-N-acetylglucosamine involves several enzymatic steps. It begins with the conversion of glucose-6-phosphate to glucosamine-6-phosphate by the enzyme glutamine:fructose-6-phosphate amidotransferase. Then, glucosamine-6-phosphate is phosphorylated to glucosamine-1-phosphate by phosphoglucomutase. Next, glucosamine-1-phosphate reacts with UTP (uridine triphosphate) to form UDP-glucosamine. Finally, UDP-glucosamine is acetylated by UDP-N-acetylglucosamine pyrophosphorylase to yield UDP-N-acetylglucosamine.

N-acetylneuraminic acid (sialic acid) is synthesized from UDP-N-acetylglucosamine through a series of enzymatic reactions. The process begins with the epimerization of UDP-N-acetylglucosamine to UDP-N-acetylmannosamine by the enzyme UDP-N-acetylglucosamine 2-epimerase. Then, UDP-N-acetylmannosamine reacts with pyruvate in a condensation reaction catalyzed by N-acetylmannosamine kinase. The resulting product, N-acetylneuraminic acid 9-phosphate, is then dephosphorylated to yield N-acetylneuraminic acid.

A pentasaccharide core is commonly found in all N-linked oligosaccharides. This core structure consists of three mannose residues, one N-acetylglucosamine residue, and one GlcNAc residue. The pentasaccharide core serves as a foundation for the further elaboration of the N-linked oligosaccharides into various structures.

The biosynthesis of the lipid-linked oligosaccharide intermediate begins with the assembly of a dolichol phosphate-linked precursor in the endoplasmic reticulum (ER). This precursor is sequentially modified by the addition of sugar residues, including N-acetylglucosamine, mannose, and glucose, from various sugar donors, such as UDP-GlcNAc, GDP-mannose, and dolichol phosphate mannose. Once the full lipid-linked oligosaccharide intermediate is assembled, it is transferred to an asparagine residue on a nascent polypeptide chain in the ER lumen.

The oligosaccharide processing on newly synthesized glycoproteins involves a series of enzymatic modifications that occur in the ER and Golgi apparatus. The initial processing step involves the removal of glucose residues from the lipid-linked oligosaccharide intermediate. Subsequently, mannose residues may be removed or added, and the oligosaccharide can be further glycosylated with various sugar residues, such as N-acetylglucosamine, galactose, sialic acid, or fucose. This processing results in the generation of diverse oligosaccharide structures with specific functions.

Peptidoglycan, a major component of bacterial cell walls, is synthesized by the sequential addition of N-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG) units. The synthesis proceeds in the cytoplasm, where UDP-NAM and UDP-NAG are activated. The activated NAM and NAG units are then transferred to a lipid carrier, undecaprenyl phosphate, forming a lipid-linked disaccharide. This disaccharide is further modified by the addition of a pentapeptide tail and translocated to the outer leaflet of the plasma membrane. Finally, the disaccharide-pentapeptide units are incorporated into the growing peptidoglycan polymer.

Penicillin, a well-known antibiotic, inhibits the synthesis of peptidoglycan by targeting the transpeptidase enzyme, which is responsible for cross-linking peptidoglycan chains. Penicillin resembles the natural substrate of the transpeptidase enzyme, allowing it to bind to the enzyme's active site and form an inactive complex, effectively preventing the cross-linking of peptidoglycan chains and inhibiting bacterial cell wall synthesis.

The repeating oligosaccharide unit of the O antigen of Salmonella typhimurium is synthesized by a series of enzymatic steps. The initial reactions occur within the inner membrane, where the oligosaccharide unit is assembled. The assembled unit is then transferred to the outer leaflet of the outer membrane, where it is incorporated into the growing polysaccharide chain. The O antigen is a major virulence factor for Salmonella, contributing to the bacterium's ability to evade the host's immune system.