Medicinal and Pharmaceutical Chemistry: Carbohydrates II

Carbohydrates Overview

• Definition: Carbohydrates are organic compounds consisting of carbon, hydrogen, and oxygen, usually with a hydrogen-oxygen atom ratio of 2:1.

• Key Types of Carbohydrates:

  • Monosaccharides: Single sugar units (e.g., glucose, fructose).

  • Disaccharides: Two monosaccharides linked together (e.g., sucrose, lactose, maltose).

  • Polysaccharides: Long chains of monosaccharide units (e.g., starch, glycogen, cellulose).

Learning Outcomes for MEDCHEM.22

• Explain the concept of mutarotation.

• Recall reactions of monosaccharides including oxidation and glycoside formation.

• Define glycosidic linkage and its importance in carbohydrates.

• Identify the structures of disaccharides like maltose, cellobiose, lactose, and sucrose.

• Understand the biochemical implications of lactose intolerance and galactosemia.

• Recognize the structures of ribose, 2’-deoxyribose, and glucosamine, and their biological significance.

• Explain carbohydrate roles in cell recognition processes.

D-Glucose Anomers

• Anomers: Two diastereomers of D-Glucose, $ ext{α}$ and $ ext{β}$, exhibit different physical/optical properties:

  • α-D-Glucose:

  • Melting Point: 150°C

  • Specific Rotation: +19°

  • β-D-Glucose:

  • Melting Point: 146°C

  • Specific Rotation: +112°

Mutarotation

• Definition: The interconversion between α- and β-anomers of a sugar when in solution.

• Unique states:

  • Each anomer is stable in solid form, but, in solution, they can equilibrate through ring opening to the linear structure.

  • Equilibrium Ratio: At equilibrium with a 50:50 anomer ratio, a specific rotation of 65.5° is observed (actual: 52.2°). The β-form is favored due to more stable anomeric hydroxyl position.

Reactions of Monosaccharides

• Oxidation:

  • Aldoses (like glucose) can be oxidized to carboxylic acids (aldonic acids).

• Oxidizing Agents:

  • Tollen's Reagent: Ag+ in ammonia, produces metallic silver.

  • Fehling's Reagent: Copper (Cu²⁺) producing a reddish precipitate of Cu₂O.

  • Benedict's Reagent: Similar to Fehling's, detects glucose in diabetes tests.

Glycoside Formation

• Hemiacetals react with alcohols in the presence of acid catalysts to yield stable acetals called glycosides.

• Glycosidic bonds form between anomeric carbon of one sugar and hydroxyl of another.

Disaccharides

• Disaccharides consist of two monosaccharides linked by glycosidic links. Most notably:

  • Maltose (B1-(1→4)-glycoside bond): Composed of two α-D-glucose.

  • Cellobiose (B2-(1→4)-glycoside bond): Composed of two β-D-glucose.

  • Lactose (B2-(1→4)-linkage): Composition of galactose and glucose.

Lactose Intolerance

• Occurs due to low levels of lactase leading to undigested lactose, causing fermentation by bacteria in the intestine resulting in discomfort.

Galactosemia

• Genetic disorder resulting in the buildup of galactose, which can cause significant organ damage due to metabolic dysfunctions.

Sucrose

• Common table sugar is a disaccharide consisting of glucose and fructose linked by an $ ext{α-(1→2)-β}$ glycosidic bond. It is a non-reducing sugar.

• Plays a role in dental health due to bacterial activity forming dental plaque and subsequent tooth decay.

Polysaccharides

• Types:

  • Starch (energy storage in plants) - composed of amylose and amylopectin.

  • Glycogen (energy storage in animals).

  • Cellulose (structural component in plants).

Cellulose

• Consists of D-glucose linked by β-(1→4)-glycosidic bonds, providing rigidity to plant cell walls. Cannot be digested by humans without cellulase enzyme.

Starch Structure

• Amylose: Linear structure with a-(1→4)-linkages.

• Amylopectin: Branched structure with both a-(1→4)- and a-(1→6)-linkages.

Glycogen Structure

• Similar to amylopectin but more branched, effectively serving as a glucose reserve in animals.

Carbohydrates are essential organic compounds primarily composed of carbon, hydrogen, and oxygen, which typically adhere to the empirical formula with a hydrogen-oxygen atom ratio of 2:1. They serve as a primary energy source in many organisms, playing critical roles in various biological functions and processes.

Key Types of Carbohydrates:

• Monosaccharides: These are the simplest forms of carbohydrates, consisting of single sugar units. Examples include glucose, known for its crucial role in energy metabolism, and fructose, found primarily in fruits. Monosaccharides have unique structural configurations that can exist in linear and cyclic forms.

• Disaccharides: Formed by the glycosidic linkage of two monosaccharides, disaccharides include sucrose (common table sugar), lactose (the sugar in milk), and maltose (found in malted foods). Each disaccharide has functional and physiological significance, such as providing quick energy.

• Polysaccharides: These complex carbohydrates consist of long chains of monosaccharide units, enabling them to perform various functions, including energy storage and providing structural integrity. Notable examples include starch and glycogen, which serve as energy reserves, and cellulose, which forms a protective barrier in plant cell walls.

Learning Outcomes for MEDCHEM.22:

• Ability to explain the concept of mutarotation, which is the change in optical activity due to the interconversion of anomers.

• Recall the reactions of monosaccharides, including oxidation and glycoside formation. For instance, aldoses can undergo oxidation to form carboxylic acids, influencing their reactivity.

• Define a glycosidic linkage: a covalent bond formed between a carbohydrate and another group, critical for the structure and function of disaccharides and polysaccharides.

• Identify structural representations of important disaccharides like maltose, cellobiose, lactose, and sucrose, which have implications in digestion and metabolism.

• Understand the biochemical implications of conditions such as lactose intolerance, where a deficiency of the enzyme lactase leads to gastrointestinal issues, and galactosemia, a genetic disorder characterized by the inability to metabolize galactose.

• Recognize the structures of key sugars like ribose and 2’-deoxyribose, which are foundational in nucleic acids, and glucosamine, vital for joint health.

• Explain the roles of carbohydrates in cell recognition processes, emphasized by their involvement in glycoproteins and glycolipids on cell surfaces that mediate cell-cell interactions.

D-Glucose Anomers:

• Anomers are a special type of stereoisomer that arise due to the difference in configuration at the anomeric carbon in cyclic forms of monosaccharides. In the case of D-Glucose, the two anomers, α-D-glucose and β-D-glucose, exhibit distinct chemical and physical properties:

  • α-D-Glucose: Melting Point: 150°C; Specific Rotation: +19°. It is characterized by the hydroxyl group on the anomeric carbon being in the axial position.

  • β-D-Glucose: Melting Point: 146°C; Specific Rotation: +112°. In this isomer, the hydroxyl group is positioned equatorially, resulting in greater stability and a higher specific rotation.

Mutarotation:

• Definition: Mutarotation refers to the interconversion between the α- and β-anomers of a sugar in solution, an important aspect that affects sugar reactivity and interaction.

• Unique States: Each anomer remains stable in solid form; however, in aqueous solutions, they can interconvert into one another through the temporary formation of a linear chain.

• Equilibrium Ratio: The equilibrated state shows a 50:50 mix of anomers, and the observed specific rotation of the mixture is 65.5°, reflecting the average activity; the actual measured is +52.2°. The β-anomer is sterically more favorable and thus predominates in solution.

Reactions of Monosaccharides:

• Oxidation: Aldoses, such as glucose, can be oxidized, resulting in the formation of carboxylic acids known as aldonic acids, which play roles in energy metabolism and pathway regulation.

• Oxidizing Agents:

  • Tollen's Reagent: Comprising Ag+ in ammonia, it produces metallic silver, serving as a qualitative test for aldehydes.

  • Fehling's Reagent: Contains Cu²⁺ ions, which can be reduced to form a reddish precipitate of Cu₂O, used to detect reducing sugars in clinical tests.

  • Benedict's Reagent: It functions similarly to Fehling's reagent, being widely used in urine glucose tests for diabetes monitoring.

Glycoside Formation:

• Glycosides are formed when hemiacetals react with alcohols in the presence of acid catalysts, producing stable acetals.

• Glycosidic Bonds: These pivotal connections form between the anomeric carbon of a sugar and the hydroxyl group of another molecule, fundamentally altering the sugar’s properties and reactivity.

Disaccharides:

• Disaccharides consist of two monosaccharides linked via glycosidic bonds and include:

  • Maltose: Composed of two α-D-glucose units linked by an α-1,4-glycosidic bond; important in energy generation.

  • Cellobiose: Composed of two β-D-glucose units linked by a β-1,4-glycosidic bond; relevant in the degradation of cellulose.

  • Lactose: Comprised of galactose and glucose linked via a β-1,4-linkage; critical in milk digestion.

Lactose Intolerance:

• This condition arises from insufficient production of the enzyme lactase, leading to the accumulation of undigested lactose in the gut. The resultant fermentation processes by intestinal bacteria can cause abdominal pain, bloating, and diarrhea.

Galactosemia:

• An inherited disorder characterized by the body's inability to metabolize galactose, resulting in the toxic buildup of galactose-1-phosphate that can cause severe health complications, including liver damage and neurological impairment.

Sucrose:

• Commonly known as table sugar, sucrose is a disaccharide formed from glucose and fructose linked by an α-(1→2)-β glycosidic bond. This non-reducing sugar’s relevance extends to its role in nutrition, sweetness, and energy supply.

• Its metabolism is crucial; however, excessive sugar consumption contributes to dental caries through bacterial acid production linked to tooth decay.

Polysaccharides:

• Types:

  • Starch: The primary energy storage polysaccharide in plants, composed of amylose (linear chains) and amylopectin (branched chains).

  • Glycogen: The energy storage form in animals, characterized by its highly branched structure, optimizing glucose reserve availability.

  • Cellulose: A polymer made up of β-D-glucose units linked by β-(1→4)-glycosidic bonds, vital for plant cell wall integrity, but indigestible by human enzymes, signifying dietary fiber.

Cellulose:

• Comprising long chains of D-glucose linked by β-(1→4)-glycosidic bonds, cellulose provides rigidity to plant cell walls, essential for structural support. Humans lack the cellulase enzyme needed to digest cellulose, thus it acts as an important source of dietary fiber promoting gut health.

Starch Structure:

• Amylose: Characterized by a predominantly linear structure formed by α-(1→4)-linkages.

• Amylopectin: A branched structure containing both α-(1→4)- and α-(1→6)-linkages, facilitating rapid glucose release when energy is needed.

Glycogen Structure:

• Similar in composition to amylopectin but exhibits a greater degree of branching, which optimizes its function as a dense glucose reserve in animals, allowing for quick mobilization during energy-demanding situations.

1. Explain the concept of mutarotation:
   Mutarotation is the phenomenon where a specific sugar, when dissolved in solution, can interconvert between its anomeric forms (α and β). This change in configuration occurs because the cyclic form of the sugar can revert to its linear form, allowing the anomeric carbon to adopt two different orientations. The specific rotation of the sugar changes as the mixture of α and β anomers reaches equilibrium, displaying optical activity changes. This concept is crucial for understanding sugar reactivity and behavior in biochemical pathways.

2. Recall reactions of monosaccharides including oxidation and glycoside formation:
   Monosaccharides can undergo oxidation, whereby aldoses like glucose are converted to carboxylic acids, termed aldonic acids, influencing metabolic processes. Glycoside formation occurs when hemiacetals react with alcohol under acidic conditions to produce glycosides, which are stable acetals and play important roles in biochemistry by altering sugar solubility and reactivity. These processes are fundamental for carbohydrate metabolism and function.

3. Define glycosidic linkage and its importance in carbohydrates:
   A glycosidic linkage is a covalent bond formed between the anomeric carbon of a sugar and the hydroxyl group of another molecule, typically a sugar. This bond is vital for the structure and function of polysaccharides and disaccharides, determining their digestibility, solubility, and biological roles. For example, the nature of the glycosidic bond affects how sugars are linked in starch, glycogen, and cellulose, impacting energy storage and structural integrity.

4. Identify the structures of disaccharides like maltose, cellobiose, lactose, and sucrose:
   Maltose consists of two α-D-glucose units linked by an α-1,4-glycosidic bond, providing quick energy. Cellobiose is formed from two β-D-glucose units linked by a β-1,4-glycosidic bond, significant in the breakdown of cellulose. Lactose, a sugar in milk, includes a β-1,4-linkage between galactose and glucose, which is important for lactation. Sucrose, common table sugar, comprises glucose and fructose linked by an α-(1→2)-β glycosidic bond, functioning as a major energy source without reducing properties. Understanding these structures is key to assessing their functional roles in biological systems.

5. Understand the biochemical implications of lactose intolerance and galactosemia:
   Lactose intolerance occurs when the body lacks sufficient lactase, the enzyme needed to break down lactose, resulting in undigested lactose that ferments in the intestine, causing symptoms like bloating and diarrhea. Galactosemia is a genetic disorder leading to an inability to metabolize galactose, causing its accumulation, which can lead to severe health issues, including liver damage and development of cataracts. Both conditions underscore the importance of proper carbohydrate metabolism.

6. Recognize the structures of ribose, 2’-deoxyribose, and glucosamine, and their biological significance:
   Ribose is a five-carbon sugar essential for RNA structure, facilitating genetic information transfer. 2’-deoxyribose, the sugar in DNA, is crucial for hereditary material storage. Glucosamine is an amino sugar critical for glycosaminoglycan synthesis, playing a vital role in maintaining joint health and structural integrity of cartilage. Understanding these sugars is paramount in molecular biology and biochemistry.

7. Explain carbohydrate roles in cell recognition processes:
   Carbohydrates, primarily in the form of glycoproteins and glycolipids on cell surfaces, are essential for cell recognition processes. They mediate interactions between cells, enabling immune response, tissue development, and signaling pathways. The specificity of these interactions can influence cellular behavior and are fundamental in processes such as fertilization and pathogen recognition. Understanding these roles can offer insights into various diseases and therapeutic strategies.