Comprehensive Biochemistry of Carbohydrates: Structure, Isomerism, and Metabolism

• General Introduction to Life and Learning

• Life Lessons and Adversity:

  • An empty pocket is described as teaching a person a million things in life.

  • Conversely, a full pocket is said to spoil an individual in "a million wars."

Definition and Classification of Carbohydrates

• Chemical Definition:

  • Carbohydrates are polyhydroxy aldehydes or ketones, or substances that yield these compounds upon hydrolysis.

  • Aldose: A carbohydrate containing an aldehyde group.

  • Ketose: A carbohydrate containing a ketone group.

• Empirical Formula:

  • Many simpler carbohydrates follow the empirical formula $(CH_2O)_n$, leading to the name "hydrate of carbon."

• Simplest Examples ($C_3H_6O_3$ or $(CH_2O)_3$):

  • Glyceraldehyde: An aldotriose containing an aldehyde group.

  • Dihydroxyacetone: A ketotriose containing a keto group.

• Classification by Number of Carbons:

  • Trioses (3 Carbons): Example: Glyceraldehyde.

  • Tetroses (4 Carbons): Example: Erythrose.

  • Pentoses (5 Carbons): Example: Ribose.

  • Hexoses (6 Carbons): Examples: Glucose, Fructose.

  • Heptoses (7 Carbons): Example: Sedoheptulose.

  • Nonoses (9 Carbons): Example: Neuraminic acid.

Polymerization and Complexity

• Monosaccharides: Single sugar units that cannot be hydrolyzed into simpler forms.

• Oligosaccharides:

  • Hydrolyzable polymers composed of $2$ to $6$ monosaccharides.

  • Disaccharides: Composed of exactly $2$ monosaccharides. Examples include Sucrose and Lactose.

• Polysaccharides:

  • Hydrolyzable polymers composed of more than $6$ monosaccharides.

  • Homopolysaccharides: Polymers consisting of a single type of monosaccharide unit. Examples: Glycogen, Cellulose, Starch.

  • Heteropolysaccharides: Polymers consisting of at least two different types of monosaccharide units or their derivatives. Example: Glycosaminoglycans (GAGs).

Structural Isomerism

• Definition: Compounds with the same molecular formula but different structural arrangements.

• Functional Group Isomers:

  • Isomers that possess different functional groups.

  • Example: Glyceraldehyde (aldehyde) and Dihydroxyacetone (ketone).

• Positional Isomers:

  • Isomers with substituent groups located on different carbon atoms.

  • Example: $2$-Phosphoglycerate (phosphate on the second carbon) and $3$-Phosphoglycerate (phosphate on the third carbon). The chemical structures involved include $COO^--CHOPO_3^--CH_2OH$ and $COO^--CHOH-CH_2OPO_3^-$.

Stereoisomerism and Conformation

• Definition: Compounds with the same molecular formula, functional groups, and positions of groups, but differing in their spatial conformation.

• Cis-trans Isomers:

  • Results from different conformations around double bonds.

  • Fumaric acid (trans): Stereoisomer where the carboxyl groups ($COOH$) are on opposite sides.

  • Maleic acid (cis): Stereoisomer where the carboxyl groups ($COOH$) are on the same side.

• Optical Isomers (Enantiomers):

  • Results from different conformations around chiral or asymmetric carbon atoms.

  • Asymmetric Carbon: A carbon atom bonded to four different groups (A, B, D, and E).

  • Mirror Images: These isomers are non-superimposable mirror images of each other.

  • Enantiomeric Pair: The two different compounds formed by the spatial arrangement of groups around a chiral center.

• Optical Activity:

  • Dextrorotatory (+): An isomer that rotates the plane of polarized light in a clockwise direction.

  • Levorotatory (-): An isomer that rotates the plane of polarized light in a counterclockwise direction.

Absolute Configuration and Reference Standards

• Glyceraldehyde Reference:

  • The simplest monosaccharide with an asymmetric carbon used as the reference for optical isomers.

  • D-Glyceraldehyde: Defined as the isomer with the hydroxyl group ($OH$) on the right when the aldehyde group is at the top in a Fischer projection. It is dextrorotatory, denoted as $D(+)$-Glyceraldehyde.

  • L-Glyceraldehyde: The isomer with the hydroxyl group on the left.

• Calculation of Optical Isomers:

  • If a compound has $n$ asymmetric carbon atoms, it has $2^n$ different optical isomers.

• Asymmetric Carbons and Isomer Counts:

  • Aldoses:

    • $3$ carbons: $1$ asymmetric carbon; $2$ isomers.

    • $4$ carbons: $2$ asymmetric carbons; $4$ isomers.

    • $5$ carbons: $3$ asymmetric carbons; $8$ isomers.

    • $6$ carbons: $4$ asymmetric carbons; $16$ isomers.

  • Ketoses:

    • $3$ carbons: $0$ asymmetric carbons; no optical isomerism.

    • $4$ carbons: $1$ asymmetric carbon; $2$ isomers.

    • $5$ carbons: $2$ asymmetric carbons; $4$ isomers.

    • $6$ carbons: $3$ asymmetric carbons; $8$ isomers.

• D and L Designations:

  • Designate the absolute configuration of the asymmetric carbon atom farthest from the aldehyde or ketone group.

  • Example Erythrose: $D$-Erythrose vs. $L$-Erythrose.

  • Example Threose: $D$-Threose vs. $L$-Threose.

Diastereomers, Epimers, and Anomers

• Diastereomers: Optical isomers that are not mirror images (enantiomers) of each other.

• Epimers:

  • Diastereomers that differ in configuration at only a single asymmetric carbon atom.

  • D-Glucose ($C_6H_{12}O_6$): Used as a baseline for comparison.

  • D-Mannose: The $C_2$ epimer of Glucose.

  • D-Galactose: The $C_4$ epimer of Glucose.

  • Note: $D$-Fructose is a ketose hexose ($C_6H_{12}O_6$) and $D$-Ribose is a pentose ($C_5H_{10}O_5$).

• Anomers and Ring Formation:

  • When carbohydrates form rings involving the aldehyde or ketone carbon, that carbon becomes asymmetric.

  • Anomeric Carbon: The newly asymmetric carbon atom.

  • Anomeric Hydroxyl Group: The hydroxyl group bound to the anomeric carbon.

  • $\alpha$-anomer: In Haworth formulas for $D$-pentoses/hexoses, the hydroxyl is below the ring plane.

  • $\beta$-anomer: The hydroxyl is above the ring plane.

  • Ring Types:

    • Pyranose: A $6$-membered ring.

    • Furanose: A $5$-membered ring.

• Mutarotation:

  • The spontaneous conversion between $\alpha$ and $\beta$ anomers in solution.

  • Equilibrium of D-Glucose: Approximately $36\%$ $\alpha$-anomer, $63\%$ $\beta$-anomer, and less than $1\%$ open-chain form.

Chemical Properties: Reducing Sugars

• Definition: Carbohydrates with a free or potentially free aldehyde or ketone group.

• Detection: Benedict's solution is used to identify reducing sugars.

• Reaction Mechanism:

  • Sugars like Glucose or Fructose in an alkaline medium form an Enediol intermediate.

  • The aldehyde group is oxidized to a carboxyl group (e.g., Glucose to Gluconic acid).

  • The reagent's cupric ions ($Cu^{2+}$) are reduced to cuprous ions ($Cu^+$), forming a precipitate of cuprous oxide ($Cu_2O$).

Glycosidic Bonds

• Definition: A bond formed between the anomeric carbon of a carbohydrate and another group.

  • O-glycosidic bond: Between the anomeric carbon and the hydroxyl oxygen of an alcohol.

  • N-glycosidic bond: Between the anomeric carbon and the nitrogen of an amine.

• Implications:

  • Glycosidic bonds link monosaccharides into oligosaccharides and polysaccharides.

  • Once the bond is formed, the ring involving the anomeric carbon is stabilized; it no longer has a potentially free aldehyde or keto group at that specific carbon.

• Reducing vs. Non-reducing sugars:

  • Reducing Sugars: Lactose, Glucose, and Isomaltose. They possess a non-reducing end and a reducing end.

  • Non-reducing Sugars: Sucrose (where the anomeric carbons of both glucose and fructose are involved in the bond).

Polysaccharide Structure and Function

• Starch:

  • Amylose: A linear polymer of glucose units linked by $\alpha(1\rightarrow 4)$ glycosidic bonds.

  • Amylopectin: A branched polymer of glucose. It contains linear $\alpha(1\rightarrow 4)$ bonds and branch points with $\alpha(1\rightarrow 6)$ glycosidic bonds.

• Glycogen:

  • The primary storage molecule in animals. It is highly branched and more compact than starch. It utilizes $\alpha(1\rightarrow 4)$ bonds for chains and $\alpha(1\rightarrow 6)$ bonds for branches.

• Cellulose:

  • A linear chain of $D$-glucose units connected by $\beta(1\rightarrow 4)$ glycosidic linkages. It is a major structural component in plants.

• Comparison of Polysaccharides:

  • Homopolysaccharides: Storage (starch, glycogen) or structural (cellulose) components consisting of one monosaccharide type.

  • Heteropolysaccharides: Composed of two or more distinct monosaccharide types, often including amino sugars or acidic sugars.

    • Glycosaminoglycans (GAGs): Linear, negatively charged molecules (e.g., Heparin, Hyaluronic acid) that act as lubricants.

    • Peptidoglycan: Structural component of bacterial cell walls.

    • Agar: Derived from seaweed, used for moisture retention.

Glycosaminoglycans (GAGs) and Proteoglycans

• Composition:

  • Large complexes of negatively charged heteropolysaccharides.

  • Repeating disaccharide units: $[acidic\,sugar\,-\,amino\,sugar]_n$.

  • Amino Sugar: Either $D$-glucosamine or $D$-galactosamine (usually acetylated).

  • Acidic Sugar: Either $D$-gluconic acid or $L$-iduronic acid.

  • Charge: Negative charge at physiological $pH$ due to carboxyl and sulfate groups.

• Proteoglycans: Formed when GAGs associate with a small amount of protein ($<5\%$).

• Physical Properties:

  • Ability to bind large amounts of water.

  • Forms a gel-like matrix.

  • Viscous, lubricating, and shock-absorbing.

Glycoproteins

• Function:

  • Cell-surface molecules serving as antigen determinants.

  • Mediators of cell-cell interaction.

  • Most serum proteins are glycosylated.

• Example: Erythropoietin:

  • Glycosylation enhances its stability in the blood.

• Building Blocks: Multi-sugar complexity involving Glucose, Galactose, Mannose, $N$-acetyl glucosamine, $N$-acetyl galactosamine, $N$-acetyl mannoseamine, Fucose, and $N$-acetylneuraminic acid.

Carbohydrate Digestion

• Dietary Sources:

  • Digestible: Starch, Sucrose, Glucose, Fructose, Lactose.

  • Non-digestible (by humans): Cellulose and other plant polysaccharides.

• Mechanism: Digestion involves the hydrolysis of polysaccharides and oligosaccharides into monosaccharides. Only monosaccharides are absorbed into the bloodstream.

• Key Digestive Enzymes:

  • $\alpha$-Amylase (Salivary gland/Pancreas): Acts on starch and glycogen to produce oligosaccharides.

  • Dextrinase (Small Intestine): Acts on oligosaccharides to produce glucose.

  • Isomaltase (Small Intestine): Acts on $\alpha(1\rightarrow 6)$ glucosides to produce glucose.

  • Maltase (Small Intestine): Acts on maltose to produce glucose.

  • Lactase (Small Intestine): Acts on lactose to produce galactose and glucose.

  • Sucrase (Small Intestine): Acts on sucrose to produce fructose and glucose.

• Pathology: Lactase deficiency results in Lactose Intolerance.

Absorption and Blood Glucose Regulation

• Absorption by Intestinal Mucosal Cells:

  • Glucose and Galactose: Enter mucosal cells from the intestinal lumen via active transport, coupled with the uptake of $Na^+$ ions.

  • Fructose: Enters via facilitated transport through the transporter protein GLUT-5.

  • Exit to Portal Circulation: All major monosaccharides exit the mucosal cells into the portal circulation via facilitated transport through the transporter GLUT-2.

• Blood Glucose Concentrations:

  • Measurements: Expressed in $mmol/L$ (or $mM$) or $mg/dL$.

  • Conversion: $1\,mM = 18\,mg/dL$.

  • Normal Levels: Roughly $3.9$ to $8.3\,mM$.

  • Hypoglycemia: Defined as blood glucose levels below $2.2\,mM$.

  • Diabetes:

    • Fasting levels above $7.0\,mM$.

    • Levels above $11.1\,mM$ measured $2$ hours after ingestion of $75\,g$ of glucose.