Carbohydrate Structure and Function

Monosaccharides and Their Classification

Carbohydrates are essential biomolecules that serve as energy sources, structural components, and recognition elements in cells. The simplest carbohydrates are monosaccharides, which can be classified based on the number of carbon atoms and the type of carbonyl group present.

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

• Oligosaccharides: Short chains of monosaccharides (2-10 units).

• Polysaccharides: Long chains, e.g., starch, glycogen, cellulose.

• Homopolysaccharides: Composed of one type of monosaccharide.

• Heteropolysaccharides: Composed of different monosaccharides.

• Glycan: General term for oligo- and polysaccharides.

The general formula for carbohydrates is .

Classification by Carbonyl Group

• Aldose: Contains an aldehyde group (e.g., glyceraldehyde).

• Ketose: Contains a ketone group (e.g., dihydroxyacetone).

Chirality and Stereochemistry

• Monosaccharides often have chiral centers, leading to D and L isomers.

• Fischer projections are used to represent stereochemistry.

• D isomers are predominant in biological systems.

Ring Formation and Anomers

• Monosaccharides cyclize to form rings (pyranose: 6-membered, furanose: 5-membered).

• Ring closure creates a new chiral center (anomeric carbon), resulting in alpha and beta anomers.

• Alpha: OH on anomeric carbon is down; Beta: OH is up.

Isomer Types

• Enantiomers: Mirror images (D vs. L).

• Diastereomers: Not mirror images.

• Anomers: Differ at the anomeric carbon (alpha vs. beta).

• Epimers: Differ at one carbon other than the anomeric carbon.

Monosaccharide Derivatives and Modifications

• Phosphorylation: Addition of phosphate (e.g., glucose-6-phosphate) for metabolic regulation.

• Oxidation: Forms acids (e.g., gluconic acid, glucuronic acid).

• Reduction: Forms sugar alcohols (e.g., sorbitol).

• Amino sugars: Addition of amino groups (e.g., N-acetylglucosamine).

• O-glycosides: Formation of glycosidic bonds via dehydration.

Disaccharides and Glycosidic Bonds

Disaccharides are formed by joining two monosaccharides via a glycosidic bond.

• Bond specificity: Defined by the carbons involved and the alpha/beta configuration.

• Examples:

  • Maltose: Alpha-1,4 bond between two glucoses.

  • Sucrose: Alpha-1,2 bond between glucose and fructose.

  • Lactose: Beta-1,4 bond between galactose and glucose.

  • Cellobiose: Beta-1,4 bond between two glucoses (not digestible by humans).

• Reducing vs. Non-reducing sugars: If a free anomeric carbon is present, the sugar is reducing.

Polysaccharides: Structure and Function

• Starch: Plant storage polysaccharide; consists of amylose (linear, alpha-1,4) and amylopectin (branched, alpha-1,6).

• Glycogen: Animal storage polysaccharide; highly branched (alpha-1,4 and alpha-1,6).

• Cellulose: Structural polysaccharide in plants; beta-1,4 linkages, forms strong fibers.

• Chitin: Structural polysaccharide in arthropods; beta-1,4 linkages of N-acetylglucosamine.

Metabolic Pathways: Overview

Metabolism: Catabolism and Anabolism

Metabolism encompasses all chemical reactions in the cell, divided into:

• Catabolism: Breakdown of molecules for energy (e.g., glycolysis, citric acid cycle).

• Anabolism: Synthesis of molecules (e.g., gluconeogenesis, fatty acid synthesis).

Central metabolic pathways funnel into the citric acid cycle, which connects carbohydrate, fat, and protein metabolism.

Glycolysis

Overview and Phases

Glycolysis is the anaerobic breakdown of glucose to pyruvate, generating ATP and NADH. It occurs in the cytoplasm and is common to both aerobic and anaerobic organisms.

• Phase 1 (Energy Investment): Uses 2 ATP to phosphorylate glucose and fructose intermediates.

• Phase 2 (Energy Payoff): Produces 4 ATP and 2 NADH per glucose (net gain: 2 ATP, 2 NADH).

Key Steps and Enzymes

• Hexokinase: Phosphorylates glucose to glucose-6-phosphate.

• Phosphofructokinase (PFK): Phosphorylates fructose-6-phosphate to fructose-1,6-bisphosphate; major regulatory point.

• Aldolase: Cleaves fructose-1,6-bisphosphate into DHAP and GAP.

• Glyceraldehyde-3-phosphate dehydrogenase: Generates NADH.

• Phosphoglycerate kinase and pyruvate kinase: Generate ATP via substrate-level phosphorylation.

Regulation of Glycolysis

• Regulated at hexokinase, PFK, and pyruvate kinase steps.

• Allosteric effectors include ATP (inhibitor), AMP/ADP (activators), citrate (inhibitor), and fructose-2,6-bisphosphate (activator).

• Hormonal regulation via insulin and glucagon affects PFK2 and fructose-2,6-bisphosphate levels.

Fermentation Pathways

• Lactic acid fermentation: Pyruvate reduced to lactate; regenerates NAD+.

• Alcoholic fermentation: Pyruvate converted to ethanol and CO2 (in yeast).

Gluconeogenesis

Overview

Gluconeogenesis is the synthesis of glucose from non-carbohydrate precursors (e.g., lactate, amino acids, glycerol), primarily in the liver.

• Shares most steps with glycolysis, but bypasses the three irreversible steps using unique enzymes:

• Hexokinase replaced by glucose-6-phosphatase.

• Phosphofructokinase replaced by fructose-1,6-bisphosphatase.

• Pyruvate kinase replaced by pyruvate carboxylase and PEP carboxykinase.

Energy cost: 4 ATP, 2 GTP, 2 NADH per glucose synthesized.

Regulation

• Reciprocal regulation with glycolysis; regulated by energy status and hormones.

• Insulin inhibits gluconeogenesis; glucagon promotes it.

Citric Acid Cycle (Krebs Cycle)

Overview and Steps

The citric acid cycle is a central pathway in aerobic metabolism, oxidizing acetyl-CoA to CO2 and generating NADH, FADH2, and GTP/ATP. It occurs in the mitochondrial matrix.

• Acetyl-CoA (2C) + Oxaloacetate (4C) → Citrate (6C)

• Two decarboxylations per cycle; returns to oxaloacetate.

• Per acetyl-CoA: 3 NADH, 1 FADH2, 1 GTP/ATP.

• Per glucose (2 acetyl-CoA): 6 NADH, 2 FADH2, 2 GTP/ATP.

Key Enzymes and Cofactors

• Pyruvate dehydrogenase complex: Converts pyruvate to acetyl-CoA; requires TPP, lipoamide, CoA, NAD+, FAD.

• Alpha-ketoglutarate dehydrogenase: Similar mechanism to PDH.

Regulation

• Regulated by energy status: ATP, NADH, acetyl-CoA inhibit; ADP, pyruvate activate.

• Product inhibition and phosphorylation control PDH activity.

Electron Transport Chain and Oxidative Phosphorylation

Overview

The electron transport chain (ETC) is a series of protein complexes (I-IV) embedded in the inner mitochondrial membrane, responsible for transferring electrons from NADH and FADH2 to oxygen, generating a proton gradient used by ATP synthase (complex V) to produce ATP.

• Complex I: Accepts electrons from NADH.

• Complex II: Accepts electrons from FADH2 (tethered from citric acid cycle).

• Coenzyme Q (ubiquinone): Lipid-soluble electron carrier between complexes I/II and III.

• Complex III: Transfers electrons to cytochrome c.

• Cytochrome c: Soluble electron carrier to complex IV.

• Complex IV: Transfers electrons to oxygen, forming water.

• ATP Synthase (Complex V): Uses proton gradient to synthesize ATP.

Mechanism

• Electron transfer is driven by increasing reduction potential; oxygen is the ultimate electron acceptor.

• Protons are pumped into the intermembrane space, creating a gradient.

• Proton flow through ATP synthase induces conformational changes, producing ATP.

Energetics

• Each NADH yields ~2.5 ATP; each FADH2 yields ~1.5 ATP.

• Overall, complete oxidation of glucose yields ~32 ATP.

Key Equations

• Relationship between reduction potential and free energy:

• Where = number of electrons, = Faraday constant, = difference in reduction potential.

Pentose Phosphate Pathway

Overview

The pentose phosphate pathway (PPP) is an alternative pathway for glucose metabolism, generating NADPH and ribose-5-phosphate for biosynthetic reactions.

• Oxidative phase: Generates NADPH.

• Non-oxidative phase: Produces ribose-5-phosphate for nucleotide synthesis.

Regulation and Integration of Metabolism

Regulatory Mechanisms

• Metabolic pathways are regulated by allosteric effectors, covalent modification (phosphorylation), and hormones (insulin, glucagon).

• Reciprocal regulation prevents futile cycles (e.g., glycolysis vs. gluconeogenesis).

• Key regulatory enzymes are often at pathway branch points or energy-consuming steps.

Summary Table: Key Carbohydrate Metabolic Pathways

Key Terms and Concepts

• ATP: Main energy currency; hydrolysis releases energy ( kJ/mol).

• NADH/FADH2: Electron carriers; deliver electrons to ETC.

• Reduction potential: Determines electron flow direction.

• Allosteric regulation: Enzyme activity modulated by effectors binding at sites other than the active site.

• Hormonal regulation: Insulin and glucagon control blood glucose and metabolic pathway activity.

Example: During fasting, gluconeogenesis is activated in the liver to supply glucose to the brain; during feeding, glycolysis is promoted to utilize incoming glucose.

Additional info: This guide expands on the original notes with definitions, pathway summaries, regulatory mechanisms, and key equations to provide a comprehensive overview suitable for biochemistry exam preparation.