Biochemistry - Lecture 1: Carbohydrates of Biological Importance

Chemical Nature and Biomedical Importance of Carbohydrates

• Chemical Nature of Carbohydrates:

  • Definition: Carbohydrates are polyhydroxyalcohols containing a carbon chain rich in hydroxyl groups ($-OH$) paired with either a functional aldehyde group or a functional ketone group.

  • Functional Groups:

    • Aldehyde group ($-CHO$): Located on the first carbon ($C_1$).

    • Keto group ($C=O$): Located on the second carbon ($C_2$).

  • Empirical Formula: Derived from carbon and water as $C_n(H_2O)_n$.

  • Representative Formula Example: Glucose is $C_6H_{12}O_6$, representing $6\,\text{C} + 6\,\text{H}_2\text{O}$.

  • Structural Comparison:

    • Glucose: Contains an aldehyde group on $C_1$.

    • Fructose: Contains a keto group on $C_2$.

• Biomedical Importance:

  • Carbohydrates are the most abundant and widely utilized organic molecules found in biological nature.

  • Dietary Energy Source: Provide a massive fraction of dietary calories for most living organisms.

  • Energy Storage: Stored internally within tissues (e.g., as glycogen) to meet future metabolic energy demands.

  • Cell Membrane Structure & Communication: Form structural membrane complexes by combining with proteins to yield glycoproteins.

  • Intercellular Signaling: Oligosaccharide chains extend outward from cell membranes like sugar "antennae," facilitating cell-to-cell recognition, adhesion, and communication.

Classification of Carbohydrates

• Classification Hierarchy based on Sugar Units:

  • Monosaccharides: Consist of a single ($1$) sugar unit. Examples include Glucose, Fructose, and Galactose.

  • Disaccharides: Composed of two ($2$) linked monosaccharide units. Examples include Maltose, Sucrose, and Lactose.

  • Oligosaccharides: Consist of short chains ranging from three to ten ($3\text{--}10$) sugar units.

  • Polysaccharides: Composed of long polymers exceeding ten ($> 10$) sugar units. Examples include Starch, Glycogen, and Cellulose.

Monosaccharides Overview and Classification

• General Definition: Monosaccharides are the simplest carbohydrate units. They cannot be hydrolyzed further into smaller simple sugars.

• Primary Classification Criteria:

  1. Number of Carbon Atoms:

     • Trioses: $3\,\text{carbons}$ ($3\,\text{C}$)

     • Tetroses: $4\,\text{carbons}$ ($4\,\text{C}$)

     • Pentoses: $5\,\text{carbons}$ ($5\,\text{C}$)

     • Hexoses: $6\,\text{carbons}$ ($6\,\text{C}$)

  2. Functional Group Type:

     • Aldehyde group ($-CHO$) $\rightarrow$ Aldoses

     • Ketone group ($C=O$) $\rightarrow$ Ketoses

  3. Combined System Naming Examples:

     • Aldehyde group + $5\,\text{C}$ = aldopentose

     • Aldehyde group + $6\,\text{C}$ = aldohexose (e.g., Glucose)

Aldoses (I – Aldoses)

• Structural Characteristics of Aldoses:

  • Contain an aldehyde functional group ($-CHO$) positioned specifically on C_1$.\n * **Mother Compound:** The parent compound from which all aldoses are derived is the aldotriose **glyceraldehyde**.\n* **Stereochemistry and Optical Isomerism (\text{D-}$and$\text{L-} Configurations):**\n * **Penultimate Carbon Rule:** Determined by examining the configuration around the carbon located directly above the terminal -CH_2OH group (the carbon preceding the last carbon atom).\n * **\text{D-}$Sugar:** Hydroxyl group ($-OH) on the penultimate carbon points to the **right**.\n * **\text{L-}$Sugar:** Hydroxyl group ($-OH) on the penultimate carbon points to the **left**.\n * **Biological Prevalence:** The vast majority of monosaccharides found naturally in human biochemistry and living organisms exist in the **\text{D-} configuration**.\n* **Aldotrioses (3\,\text{C}):**\n * \text{D-Glyceraldehyde}$: Hydroxyl group on$C_2 points to the right.\n * \text{L-Glyceraldehyde}$: Hydroxyl group on$C_2 points to the left.\n\n\n\n* **Subclassification of Aldoses by Carbon Length:**\n * **Aldotrioses (3\,\text{C}):** Glyceraldehyde.\n * **Aldotetroses (4\,\text{C}$):**$\text{D-Erythrose}$($-OH$groups on$C_2$and$C_3 both point to the right).\n * **Aldopentoses (5\,\text{C}):**\n * \text{D-Ribose}$: Hydroxyl groups on$C_2$,$C_3$, and$C_4 all point to the right.\n * \text{D-Xylose}$: Hydroxyl group on$C_3$points to the left, while$C_2$and$C_4 point to the right.\n * **Aldohexoses (6\,\text{C}):**\n * \text{D-Glucose}$: Hydroxyl group orientation pattern from$C_2$to$C_5$is **Right • Left • Right • Right** ($\text{R} \cdot \text{L} \cdot \text{R} \cdot \text{R}).\n * \text{D-Mannose}$: Inversion at$C_2$relative to glucose ($-OH$on$C_2$points left). Mannose is the **$C_2 epimer of glucose**.\n * \text{D-Galactose}$: Inversion at$C_4$relative to glucose ($-OH$on$C_4$points left). Galactose is the **$C_4 epimer of glucose**.\n\n\n\n* **Epimer Relationship Rules:**\n * **Definition:** Epimers are two stereoisomers that differ in chemical configuration around **only one specific asymmetric carbon atom** (excluding the anomeric carbon).\n * **Important Distinctions:**\n * Glucose and Mannose are C_2 epimers.\n * Glucose and Galactose are C_4 epimers.\n * **Crucial Exam Note:** Mannose and Galactose are **NOT epimers** of each other because they differ in configuration at two carbon positions (C_2$and$C_4).\n* **Fischer Projection Drawing Conventions:**\n * The continuous vertical line represents the central carbon backbone (C_1 = -CHO$drawn at the top;$-CH_2OH at the bottom).\n * Each horizontal intersection (cross) denotes a central carbon atom bound to a hydrogen atom (-H$) and a hydroxyl group ($-OH) on its left and right sides.\n\n# Ketoses (II – Ketoses)\n\n* **Structural Characteristics of Ketoses:**\n * Contain a carbonyl keto group (C=O$) embedded internally within the carbon chain, specifically at position$C_2$.

  • Simplest Ketose: Dihydroxyacetone (DHA), a three-carbon ketotriose.

  • Absence of Chirality in DHA: Dihydroxyacetone possesses no asymmetric carbon atom; consequently, it cannot exist in $\text{D-}$ or $\text{L-}$ optical forms.

• Nomenclature Rule:

  • The systematic names of ketose sugars typically end with the suffix "-ulose" (e.g., ribulose, xylulose, erythrulose, sedoheptulose).

  • Exception: Fructose is an exception to the "-ulose" naming convention.

• Subclassification of Ketoses by Carbon Length:

  • Ketotrioses ($3\,\text{C}$): Dihydroxyacetone (DHA).

  • Ketotetroses ($4\,\text{C}$): $\text{D-Erythrulose}$.

  • Ketopentoses ($5\,\text{C}$): $\text{D-Ribulose}$, $\text{D-Xylulose}$.

  • Ketohexoses ($6\,\text{C}$): $\text{D-Fructose}$.

  • Ketoheptoses ($7\,\text{C}$): $\text{D-Sedoheptulose}$ ($7\,\text{carbons}$).

• Key Distinction Between Aldoses and Ketoses:

  • Aldose: Carbonyl group ($C=O$) is terminal, positioned at C_1$.\n * **Ketose:** Carbonyl group (C=O$) is internal, positioned at$C_2$.

  • Cautionary Distinction: Ribose is an aldose, whereas Ribulose is a ketose. The inclusion of the two letters "ul" marks the presence of a ketone group.

Forms of Isomerism in Monosaccharides

• General Definition of Isomers: Isomers are chemical compounds that possess identical molecular formulas but differ in structural linkage or spatial (steric) arrangement.

  • Structural Isomers: Atoms are connected in a different order or bond arrangement.

    • Example: Glyceraldehyde (an aldose) and Dihydroxyacetone (a ketose) both share the molecular formula $C_3H_6O_3$, but glyceraldehyde carries an aldehyde group while dihydroxyacetone carries a ketone group.

  • Stereoisomers: Feature identical atom connectivity and bond arrangements but differ in 3D spatial orientation (analogous to left and right hands).

• Four Major Types of Monosaccharide Isomerism:

  1. Optical Isomers ($\text{D-}$ and $\text{L-}$ Forms):

     • $\text{D-}$ and $\text{L-}$ forms represent non-superimposable mirror images of one another (enantiomers), such as $\text{D-glyceraldehyde}$ and $\text{L-glyceraldehyde}$.

  2. Epimers:

     • Two sugars that differ in stereochemical configuration around only one carbon atom (excluding the anomeric carbon).

     • Examples: Glucose and Mannose (differ at $C_2$); Glucose and Galactose (differ at $C_4$).

  3. Anomers (Cyclization Isomers):

     • Mechanism of Cyclization: When open-chain monosaccharides convert into cyclic ring structures, the former planar carbonyl carbon ($C=O$) undergoes nucleophilic attack to form a ring.

     • Anomeric Carbon Creation: This reaction turns the carbonyl carbon into a new asymmetric center called the anomeric carbon ($C_1$ in cyclic aldoses; $C_2$ in cyclic ketoses).

     • Configuration Types ($\alpha$ and $\beta$):

       • $\alpha$ Anomer: Hydroxyl group ($-OH$) on the anomeric carbon points down (trans / opposite side relative to the $-CH_2OH$ group).

       • $\beta$ Anomer: Hydroxyl group ($-OH$) on the anomeric carbon points up (cis / same side as the $-CH_2OH$ group).

       • Mnemonic Trick: $\beta$ = aBove $\uparrow$.

     • Anomers act as epimers specifically at $C_1$ for cyclic aldoses and $C_2$ for cyclic ketoses.

  4. Aldose-Ketose Isomers (Functional Group Isomerism):

     • Molecules sharing identical molecular formulas but differing in functional group identity (aldehyde vs. ketone).

     • Example: Glucose ($C_6H_{12}O_6$, an aldehyde) and Fructose ($C_6H_{12}O_6$, a ketone). Fructose is a functional-group isomer of glucose, galactose, and mannose.

• Summary of the Four Isomerisms at a Glance:

  • Optical: $\text{D-}$ and $\text{L-}$ enantiomers are non-superimposable mirror images.

  • Epimers: Differ in configuration at a single non-anomeric carbon.

  • Anomers: Differ in configuration exclusively at the anomeric carbon following ring cyclization.

  • Aldose-Ketose: Differ in functional group classification (aldehyde vs. ketone).

Biologically Important Monosaccharides

• Trioses ($3\,\text{C}$):

  • Glyceraldehyde 3-phosphate and Dihydroxyacetone phosphate: Key phosphorylated metabolic intermediates generated during intermediate stages of intracellular glucose oxidation (glycolysis).

• Tetroses ($4\,\text{C}$):

  • Erythrose 4-phosphate: Phosphorylated intermediate generated during cellular glucose oxidation (pentose phosphate pathway).

• Pentoses ($5\,\text{C}$):

  • $\text{D-Ribose}$: Essential structural monomer in nucleosides, nucleotides, and ribonucleic acid (RNA).

  • $\text{2-Deoxyribose}$: Core structural monosaccharide component of deoxyribonucleic acid (DNA).

• Hexoses ($6\,\text{C}$):

  • $\text{D-Glucose}$ ("Grape Sugar"):

    • Serves as the primary monosaccharide present in blood.

    • Abundantly present across all animal and plant cells, honey, and natural fruits.

    • Acts as the fundamental building block for key disaccharides and structural/storage polysaccharides.

  • $\text{D-Fructose}$ ("Fruit Sugar"):

    • Naturally found in honey, fruits, and seminal fluid (providing primary metabolic energy for sperm motility).

    • Constituent component of sucrose (table sugar) and inulin.

  • $\text{D-Galactose}$:

    • Constituent monomer of lactose (milk sugar present in dairy).

    • Integral structural component of glycosaminoglycans (GAGs), glycolipids, and glycoproteins.

Monosaccharide Derivatives

• 1. Sugar Acids:

  • Produced via the oxidation of terminal carbon groups on monosaccharides into carboxylic acid groups ($-COOH$).

  • Aldonic Acid:

    • Site of Oxidation: First carbon / aldehyde group ($C_1$: $-CHO \rightarrow -COOH$).

    • Example: Gluconic acid (derived from glucose).

  • Uronic Acid:

    • Site of Oxidation: Terminal primary alcohol group (last carbon: $-CH_2OH \rightarrow -COOH$), while maintaining the top aldehyde group intact.

    • Examples: Glucuronic acid (GlcUA, from glucose), Galacturonic acid (GalUA, from galactose).

  • Aldaric Acid:

    • Site of Oxidation: Simultaneous oxidation at both ends (aldehyde group at $C_1$ and primary alcohol at the last carbon are both oxidized to $-COOH$).

    • Example: Glucosaccharic acid (derived from glucose).

  • Memory Tip: Aldonic derived from Aldehyde ($C_1$), Uronic derived from Under (bottom carbon), and Aldaric derived from All/Both ends.

*   **$\text{L-Ascorbic Acid}$ (Vitamin C):**
    *   Synthesized from glucose oxidation in animals, but **humans cannot synthesize it** due to a lack of the required enzymatic machinery. Therefore, Vitamin C is an essential dietary requirement for humans.

• 2. Sugar Alcohols (Polyols):

  • Formed when the functional carbonyl group ($C=O$ or $-CHO$) of a sugar is reduced ($+\text{H}_2$) into an alcohol group ($-OH$), yielding a polyhydroxy molecule where every carbon carries a hydroxyl group.

  • Nomenclature: Chemical names end with the suffix "-itol".

  • Reduction Reactions:

    • Glucose $+\text{H}_2 \xrightarrow{\text{aldose reductase}}$ Sorbitol

    • Galactose $+\text{H}_2 \rightarrow$ Dulcitol

    • Mannose $+\text{H}_2 \rightarrow$ Mannitol

    • Ribose $+\text{H}_2 \rightarrow$ Ribitol

    • Glyceraldehyde or Dihydroxyacetone (DHA) $+\text{H}_2 \rightarrow$ Glycerol

    • Fructose $+\text{H}_2 \rightarrow$ Sorbitol + Mannitol

  • Mnemonic for Substrates and Polyols:

    • Sorbitol $\leftarrow$ Glucose

    • Dulcitol $\leftarrow$ Galactose

    • Mannitol $\leftarrow$ Mannose

*   **Mechanism for Dual Alcohol Yield from Fructose:**
    *   Fructose contains an internal planar carbonyl double bond ($C=O$) at C_2$.\n        *   Reduction (+\text{H}_2$) across this planar carbonyl group generates a **new asymmetric carbon atom** at position$C_2$.
    *   Hydrogen addition can occur from either side of the plane:
        *   If the newly created $-OH$ group points to the **right** $\rightarrow$ **$\text{D-Sorbitol}$** (matching reduced glucose stereochemistry).
        *   If the newly created $-OH$ group points to the **left** $\rightarrow$ **$\text{D-Mannitol}$** (matching reduced mannose stereochemistry).
    *   Aldoses do not form a new asymmetric center upon terminal $C_1$ reduction, producing only a single polyol product.
*   **Biologically Important Sugar Alcohols:**
    *   **Glycerol:** Polyol derived from glyceraldehyde or DHA. Represents the primary structural backbone of triacylglycerols (fats) and major phospholipids.
    *   **Ribitol:** Polyol derived from ribose reduction. Constituent component of riboflavin (**Vitamin $\text{B}_2$**).

• 3. Deoxysugars:

  • Defined as sugars in which a hydroxyl group ($-OH$) is replaced by a hydrogen atom ($-H$), resulting in a loss of oxygen ("deoxy").

  • Key Representative: $\text{2-Deoxyribose}$ (specifically $\text{2-deoxy-}\beta\text{-D-ribofuranose}$).

  • Structural Difference: Position $C_2'$ possesses $-H$ instead of $-OH$.

  • $\text{2-Deoxyribose}$ forms the carbohydrate backbone of DNA (deoxyribonucleic acid), while unsubstituted ribose forms RNA.

• 4. Aminosugars:

  • Formed by substituting an amino group ($-NH_2$) for the hydroxyl group ($-OH$) located at $C_2$.\n * **Nomenclature:** Names consistently terminate with the suffix **"-amine"**.\n * **Examples:** Glucosamine ($\text{GluN}$), Galactosamine ($\text{GlaN}$), Mannosamine (\text{ManN}$).\n\n\n\n * **Biological Function:** Crucial structural components in glycosaminoglycans (GAGs), complex glycolipids, and glycoproteins. Aminosugar moieties are present in numerous antibiotics and are critical for their antimicrobial mechanism.\n\n* **5. Ester Formation (Phosphate Esters):**\n * Formed via an esterification reaction between a sugar hydroxyl group (-OH$) and an acid (e.g., phosphoric acid,$-PO_3H_2$), releasing a water molecule ($-H_2O).\n * **Key Intermediates:**\n * **Glucose 1-phosphate (\text{G-1-P}$):** Phosphate esterified at$C_1$.</p><ul><li><p><strong>Glucose 6-phosphate ($\text{G-6-P}$): Phosphate esterified at $C_6$ ($-CH_2O-P$).