"Carbohydrate"

Carbohydrates are essential biomolecules composed of carbon (C), hydrogen (H), and oxygen (O), typically in the ratio of (CH₂O)n. They serve as a primary energy source, structural components, and signaling molecules in biological systems.

 

Classification of Carbohydrates

Carbohydrates are classified based on their structure and complexity:

Monosaccharides (Simple Sugars)

• The basic building blocks of carbohydrates.
• Glucose, fructose, galactose
• Classified based on:
• Number of carbon atoms: Triose (C₃), Tetrose (C₄), Pentose (C₅), Hexose (C₆), Heptose (C₇)
• Functional group:
• Aldoses (contain an aldehyde group, -CHO) → e.g., Glucose, Galactose
• Ketoses (contain a ketone group, -CO) → e.g., Fructose

Examples:

• Glucose (C₆H₁₂O₆) – Primary energy source
• Fructose – Found in fruits, sweetest monosaccharide
• Galactose – Part of lactose in milk
• Ribose & Deoxyribose – Sugar components of nucleotides (RNA, DNA)

Health Impact

• Rapidly absorbed, causing blood sugar spikes.
• Excess consumption → Insulin resistance, metabolic syndrome, fatty liver.

Disaccharides (Two Monosaccharides Linked)

Formed by glycosidic bonds through a condensation reaction (loss of water).

Sucrose (glucose + fructose), lactose (glucose + galactose), maltose (glucose + glucose)

Examples:

• Sucrose (Glucose + Fructose) – Table sugar
• Lactose (Glucose + Galactose) – Found in milk
• Maltose (Glucose + Glucose) – Produced during starch breakdown

Oligosaccharides (3-10 Monosaccharides)

• Play roles in cell signaling and glycoprotein formation.
• Examples: Raffinose, Stachyose (found in legumes - fermented by gut microbiota).

Polysaccharides (Complex Carbohydrates)

Polymers of hundreds to thousands of monosaccharides.

• Starch: Amylose (linear) vs. Amylopectin (branched, digested faster).
• Fiber: Soluble (pectin, β-glucans) vs. Insoluble (cellulose, lignin).

Health Benefits

• Slower digestion → More stable blood glucose levels.
• Fiber improves gut microbiome, lowers cholesterol, reduces colon cancer risk.

 

Types:

Storage Polysaccharides – Energy reserves

• Starch (plants) – Composed of amylose (linear) and amylopectin (branched)
• Glycogen (animals, fungi) – Highly branched for rapid glucose release

Structural Polysaccharides – Provide strength and support

• Cellulose (plants) – β(1→4) linked glucose, indigestible in humans
• Chitin (fungi, arthropod exoskeletons) – Similar to cellulose but with N-acetylglucosamine units
• Peptidoglycan (bacterial cell walls) – Made of sugar-peptide complex

 

Biochemical Importance of Carbohydrates

• Energy Production: ATP synthesis via glucose oxidation.
• Structural Role: Cell walls (plants, bacteria), exoskeletons (arthropods).
• Cell Signaling: Glycoproteins, glycolipids (cell-cell recognition).
• Genetic Material: Ribose (RNA), deoxyribose (DNA).

 

Structural & Functional Biochemistry of Carbohydrates

Anomeric Forms & Mutarotation

• α & β anomers of glucose differ at C1 hydroxyl position  (anomeric carbon).
• Mutarotation: Interconversion between α and β forms in aqueous solutions (via open-chain form).

Enzymology of Glycosidic Bonds: Formation & Hydrolysis

• α(1→4) & α(1→6) bonds in starch & glycogen.
• β(1→4) bonds in cellulose (undigestible by humans).
• Hydrolysis: Glycosidases break glycosidic bonds (e.g., amylase, lactase).
• Formation: Glycosyltransferases build glycans for glycoproteins/lipids.

Advanced Insights into Polysaccharides

• Amylose: Linear α(1→4) bonds.
• Amylopectin: Branched α(1→4), α(1→6) bonds.
• Cellulose: β(1→4) bonds, structural role in plants.
• Chitin (β-1,4 ): In fungi/insects. Modified cellulose with N-acetylglucosamine.
• Glycosaminoglycans (GAGs): Hyaluronic acid, heparin (cartilage, blood clotting).

 

Carbohydrate Metabolism

Glycolysis (Breakdown of Glucose)

• Converts glucose into pyruvate, generating ATP and NADH.
• Occurs in the cytoplasm.
• Net yield: 2 ATP, 2 NADH, 2 Pyruvate per glucose.

Glycolysis: The Breakdown of Glucose

Location: Cytoplasm
Purpose: Converts glucose (C₆H₁₂O₆) into pyruvate (C₃H₄O₃), generating ATP and NADH.

Key Steps:

1. Glucose → Glucose-6-phosphate (G6P) (Hexokinase/Glucokinase, ATP used)
2. G6P → Fructose-6-phosphate (F6P) (Phosphoglucose isomerase)
3. F6P → Fructose-1,6-bisphosphate (F1,6BP) (Phosphofructokinase-1, ATP used, rate-limiting step)
4. Cleavage into G3P + DHAP (Aldolase)
5. DHAP ↔ G3P (Triose phosphate isomerase)
6. G3P → 1,3-BPG (G3P dehydrogenase, NADH formed)
7. 1,3-BPG → 3PG (Phosphoglycerate kinase, ATP produced)
8. 3PG → 2PG → PEP (Mutase, enolase)
9. PEP → Pyruvate (Pyruvate kinase, ATP produced)

Regulation of Glycolysis:

• Hexokinase/Glucokinase (HK/GK) (EC 2.7.1.1)
• Catalyzes glucose → G6P, preventing glucose efflux.
• Glucokinase (liver/pancreas) has low affinity (high Km, sigmoidal curve), allowing regulation by glucose levels.
• Hexokinase (muscles/brain) has high affinity (low Km) for rapid phosphorylation.
• Inhibition: Hexokinase is inhibited by G6P (feedback inhibition).
• Phosphofructokinase-1 (PFK-1) (EC 2.7.1.11) (Rate-limiting step)
• Converts F6P → F1,6BP.
• Allosteric regulation:
• Activated by: AMP, Fructose-2,6-bisphosphate (F2,6BP) (insulin-mediated).
• Inhibited by: ATP, Citrate, H⁺ (lactic acidosis).
• Pyruvate Kinase (PK) (EC 2.7.1.40)
• Converts PEP → Pyruvate (final ATP-producing step).
• Regulation:
• Activated by: F1,6BP (feedforward activation).
• Inhibited by: ATP, Alanine, cAMP (glucagon-mediated phosphorylation in liver).

Fates of Pyruvate:

• Aerobic conditions: Converted into Acetyl-CoA for the TCA cycle.
• Anaerobic conditions: Reduced to lactate (via lactate dehydrogenase).

Mitochondrial ATP Generation from Carbohydrate Oxidation

• Pyruvate → Acetyl-CoA (Pyruvate dehydrogenase, PDH complex) → Enters TCA cycle → Generates NADH, FADH₂ → Electron Transport Chain (ETC) → Oxidative phosphorylation (ATP synthesis via ATP synthase).

 

Citric Acid Cycle (TCA/Krebs Cycle)

• Pyruvate enters mitochondria and is converted into Acetyl-CoA.
• Produces NADH, FADH₂, ATP, and CO₂.

 

Oxidative Phosphorylation

• Electrons from NADH & FADH₂ drive ATP synthesis via the Electron Transport Chain (ETC).
• Generates ~34 ATP per glucose.

Pentose Phosphate Pathway (PPP): Nucleotide & NADPH Synthesis

Location: Cytoplasm
Purpose: Produces NADPH (for biosynthesis, antioxidant defense) and ribose-5-phosphate (for nucleotide synthesis).

Key Phases:

• Oxidative Phase:
• G6P → 6-Phosphogluconate → Ribulose-5-phosphate (NADPH produced for fatty acid synthesis, antioxidant defense)
• Non-Oxidative Phase:
• Interconverts sugars (Ribose-5-phosphate ↔ F6P, G3P) (nucleotide synthesis).

Regulation:

• Glucose-6-phosphate dehydrogenase (G6PD): Rate-limiting enzyme, inhibited by NADPH.

• Deficiency: G6PD deficiency → Hemolytic anemia (oxidative stress).

 

Glycogenesis & Glycogenolysis

• Glycogenesis: Converts glucose to glycogen (storage form).
• Glycogenolysis: Breaks down glycogen back into glucose.

Glycogen Metabolism: Storage & Mobilization

Glycogenesis (Glycogen Synthesis)

1. Glucose → G6P (Hexokinase/Glucokinase)
2. G6P → G1P (Phosphoglucomutase)
3. G1P + UDP → UDP-glucose (UDP-glucose pyrophosphorylase)
4. UDP-glucose → Glycogen (Glycogen synthase, branching enzyme)
5. Glycogen synthase (GS) catalyzes α(1→4) glycosidic bond formation.
6. Branching enzyme (1,6 transferase): Creates α(1→6) linkages for branching.

Glycogenolysis (Glycogen Breakdown)

1. Glycogen → G1P (Glycogen phosphorylase)
2. G1P → G6P (Phosphoglucomutase)
3. G6P → Glucose (Glucose-6-phosphatase, liver only)
4. Glycogen phosphorylase: Cleaves α(1→4) bonds (releases G1P).
5. Debranching enzyme: Removes α(1→6) branches.

Glycogen Storage Diseases (GSDs)

• Von Gierke’s Disease (Type I): Glucose-6-phosphatase deficiency (severe fasting hypoglycemia).
• Pompe’s Disease (Type II): Lysosomal α-glucosidase deficiency (cardiomyopathy).
• McArdle’s Disease (Type V): Muscle phosphorylase deficiency (exercise intolerance).

Regulation:

• Glycogen synthase (synthesis): Activated by insulin
• Glycogen phosphorylase (breakdown): Activated by glucagon, epinephrine

 

Gluconeogenesis

• The synthesis of glucose from non-carbohydrate sources (e.g., amino acids, lactate).
• Occurs mainly in the liver.

Gluconeogenesis: Synthesis of Glucose

Location: Liver, kidneys
Purpose: Converts non-carbohydrate precursors (lactate, amino acids, glycerol) into glucose.

Bypassing Irreversible Steps of Glycolysis:

1. Pyruvate → Oxaloacetate (OAA) (Pyruvate carboxylase) (mitochondrial enzyme, requires biotin).
2. OAA → PEP (PEP carboxykinase) (rate-limiting, upregulated in diabetes).
3. F1,6BP → F6P (Fructose-1,6-bisphosphatase, rate-limiting) (opposes PFK-1).
4. G6P → Glucose (Glucose-6-phosphatase, only in liver/kidneys)

Regulation of Gluconeogenesis:

• Activated by glucagon, cortisol (increase PEPCK).
• Inhibited by insulin (lowers PEPCK expression).

 

Carbohydrate Digestion & Absorption

Enzymatic Breakdown

1. Salivary amylase: Begins starch digestion in mouth → Maltose, maltotriose.
2. Pancreatic amylase: Continues digestion in small intestine.
3. Brush border enzymes: Maltase, lactase, sucrase → Break disaccharides into monosaccharides.
4. Absorption: Glucose & galactose (SGLT1, Na⁺-dependent); Fructose (GLUT5, passive transport).

Carbohydrates & Energy Metabolism

• Glucose → ATP via Glycolysis, TCA Cycle, and Oxidative Phosphorylation.
• Glycemic Index (GI): Measures carbohydrate impact on blood sugar:
• High GI (70+): White bread, rice, sugary drinks → Rapid spikes.
• Low GI (<55): Whole grains, legumes, non-starchy vegetables → Sustained energy.

 

Carbohydrates in Health & Disease

• Diabetes Mellitus: Impaired carbohydrate metabolism due to insulin resistance or deficiency.
• Type 1 Diabetes: Autoimmune β-cell destruction.
• Type 2 Diabetes: Insulin resistance, linked to high carbohydrate intake & obesity.
• Insulin action: GLUT4 translocation (muscles, adipose tissue).
• Diabetes (T1D/T2D): Failure of insulin signaling.
• Lactose Intolerance: Deficiency of lactase enzyme leads to lactose malabsorption.
• Glycogen Storage Diseases: Genetic disorders affecting glycogen metabolism (e.g., McArdle’s disease).
• Von Gierke’s Disease (GSD Type I): Glucose-6-phosphatase deficiency, severe hypoglycemia.
• Pompe’s Disease (GSD Type II): Lysosomal α-glucosidase deficiency, muscle weakness.
• Obesity & Metabolic Syndrome: Excessive carbohydrate intake contributes to fat storage and insulin resistance.

Carbohydrate Metabolism in Cancer (Warburg Effect)

• Aerobic glycolysis in cancer cells (favoring lactate production despite O₂ presence).
• Hexokinase-2 upregulation enhances glucose uptake.

Carbohydrate-Glycan Interactions in Infections

• Influenza: Hemagglutinin binds sialic acid receptors on host cells.
• H. pylori: Binds gastric mucins via Lewis antigens.

 

Carbohydrate-Based Biomolecules & Therapeutics

Glycosylation & Immune Response

• Glycosylation of antibodies affects their function.
• HIV, cancer cells evade immune detection by altering glycosylation.

Glycobiology in Antibodies & Vaccines

• Monoclonal antibodies (mAbs) require glycoengineering for optimal function.

Carbohydrate-Based Biomaterials & Nanotechnology

• Heparin: Sulfated polysaccharide anticoagulant.
• Glycan-coated nanoparticles: Used in drug delivery.

 

Carbohydrate-Based Biomolecules & Therapeutics

4.1 Glycosylation in Monoclonal Antibody Engineering

• Fc glycosylation in IgG: Modifies immune response (e.g., enhances ADCC).
• Therapeutic mAbs: Need glycoengineering for optimal efficacy.

4.2 Synthetic Glycobiology for Vaccines

• Glycan-based vaccines (e.g., Pneumococcal, MenACWY meningococcal vaccines).
• HIV envelope glycans: A target for broadly neutralizing antibodies.

4.3 Carbohydrate-Based Drug Delivery & Nanotechnology

• Chitosan nanoparticles for targeted drug release.
• PEGylation (polyethylene glycol modification) enhances drug stability.

 

Advanced Topics

Carbohydrate Chemistry

• Anomeric forms: α and β anomers of glucose.
• Mutarotation: Interconversion between α and β forms in solution.
• Maillard Reaction: Reaction of sugars with amino acids leading to browning (food chemistry).

Glycobiology

• Glycosylation: Attachment of carbohydrates to proteins/lipids for function.
• Lectins & Glycan Binding: Critical in immune response, infection, and cancer.

Carbohydrate-Based Drug Development

• Heparin (anticoagulant): Sulfated polysaccharide.
• Glycomimetics: Drugs mimicking carbohydrate structures to target diseases.

 

Future Perspectives

• Synthetic Biology & Carbohydrate Engineering: Designer polysaccharides with tailored properties.
• Carbohydrate Nanotechnology: Carbohydrate-coated nanoparticles for drug delivery.
• AI-Driven Carbohydrate Research: Predicting carbohydrate interactions for precision medicine.