3.1 Metabolism, Enzymes & Oral Biochemistry

3.1 Metabolism, Enzymes & Oral Biochemistry

Quick Answer: Cells extract energy mainly by oxidizing glucose through glycolysis → pyruvate oxidation → Krebs (TCA) cycle → electron transport chain (ETC) with oxidative phosphorylation. Oral hard tissues are mineralized composites: enamel is nearly pure apatite; dentin/bone/cementum use type I collagen as the organic scaffold. Fluoride stabilizes apatite as fluorapatite and favors remineralization. Enzymes accelerate every step—from salivary digestion to matrix metalloproteinase (MMP)–mediated collagen breakdown.

Applied biomedical sciences are about 20 ± 5% of the AFK blueprint. Biochemistry items rarely ask for obscure pathways; they test whether you can link ATP production, collagen defects, enamel/dentin composition, and fluoride chemistry to caries, periodontal disease, developmental defects, and biomaterial interfaces covered later.

Cellular Energy Metabolism

Glycolysis (cytosol)

Glycolysis converts one glucose (C₆) to two pyruvate (C₃) molecules and yields a net of 2 ATP plus 2 NADH under aerobic conditions (or lactate under anaerobic conditions).

Key teaching points for AFK:

• Occurs in the cytosol; does not require oxygen
• Investment phase uses 2 ATP; payoff phase produces 4 ATP → net 2 ATP
• Rate-limiting / highly regulated steps classically include hexokinase/glucokinase, phosphofructokinase-1 (PFK-1), and pyruvate kinase
• Anaerobic fate: pyruvate → lactate (regenerates NAD⁺ so glycolysis can continue)—relevant to ischemic pulp tissue and muscle fatigue concepts
• Aerobic fate: pyruvate enters mitochondria → acetyl-CoA via the pyruvate dehydrogenase complex (links to TCA)

Dental link: Cariogenic plaque bacteria ferment dietary carbohydrates to organic acids (especially lactic acid), dropping local pH and dissolving enamel mineral. That is microbial carbohydrate metabolism applied to the tooth surface—not human glycolysis, but the same chemical theme of sugar → acid.

Krebs (Citric Acid / TCA) Cycle

Acetyl-CoA (2-carbon) condenses with oxaloacetate (4-carbon) to form citrate; through the cycle, two CO₂ are released and high-energy electron carriers are generated.

Per acetyl-CoA (approximate exam-level products):

The cycle sits in the mitochondrial matrix. Intermediates also supply biosynthetic precursors (e.g., for amino acids), so the TCA cycle is both catabolic and anaplerotic/amphibolic.

Electron Transport Chain and Oxidative Phosphorylation

The ETC is a series of complexes in the inner mitochondrial membrane:

1. NADH and FADH₂ donate electrons
2. Electrons flow through complexes I–IV to O₂, forming H₂O (oxygen is the terminal electron acceptor)
3. Proton pumping creates an electrochemical gradient across the inner membrane
4. ATP synthase uses proton re-entry to phosphorylate ADP → ATP (oxidative phosphorylation)

Rough complete aerobic yield from one glucose is classically taught near ~30–32 ATP (textbook values vary with shuttle systems); the key AFK contrast is that aerobic metabolism yields far more ATP than anaerobic glycolysis alone.

Clinical biochemistry hooks: cyanide and some toxins block cytochrome oxidase; uncouplers dissipate the proton gradient as heat; ischemia/hypoxia force anaerobic metabolism → lactate and limited ATP—relevant to pulp under deep caries or trauma when microcirculation fails.

Other Fuels (Exam-Level Only)

• β-oxidation of fatty acids yields acetyl-CoA for the TCA cycle
• Amino acid carbon skeletons enter as pyruvate, acetyl-CoA, or TCA intermediates
• Gluconeogenesis (mainly liver/kidney) makes glucose from non-carbohydrate precursors during fasting—know that it is not a simple reverse of glycolysis at all steps

Enzymes: Principles with Oral Examples

Enzymes are proteins (mostly) that lower activation energy and accelerate reactions without being consumed. They show specificity for substrates and are regulated by pH, temperature, cofactors, and inhibitors.

Oral and craniofacial enzyme examples:

• Salivary α-amylase (ptyalin): begins starch digestion to maltose/limit dextrins
• Lingual lipase: lipid digestion start (especially important in neonates)
• Carbonic anhydrase: CO₂ ⇌ HCO₃⁻ chemistry; also relevant to salivary buffering models
• Alkaline phosphatase: associated with mineralization activity in bone/cementum contexts
• Matrix metalloproteinases (MMPs) and bacterial collagenases: degrade collagen; elevated in periodontitis and involved in hybrid-layer degradation after adhesive dentistry
• Lysozyme: antimicrobial hydrolysis of bacterial cell walls in saliva

pH optima matter: enamel demineralization accelerates as plaque pH falls below the critical pH (~5.5 for hydroxyapatite; lower for fluorapatite)—an acid–mineral equilibrium concept, not an enzyme optimum, but frequently tested beside metabolic acid production.

Collagen Synthesis and Periodontal/Dentin Matrix

Type I collagen is the principal structural protein of dentin, cementum, bone, and periodontal ligament (PDL). Type III is prominent in more compliant tissues and early wound matrix; type IV is basement membrane—know type I as the hard-tissue workhorse.

Synthesis pathway (high-yield sequence)

1. Transcription/translation of α chains (pre-pro-collagen) on rough ER ribosomes
2. Hydroxylation of selected proline and lysine residues — requires vitamin C, Fe²⁺, O₂, and α-ketoglutarate
3. Glycosylation of some hydroxylysines
4. Triple-helix assembly of pro-collagen (registration peptides help alignment)
5. Secretion; extracellular cleavage of pro-peptides → tropocollagen
6. Cross-linking (lysyl oxidase, copper-dependent) → fibrils and fibers with tensile strength

Scurvy (vitamin C deficiency) impairs hydroxylation → unstable collagen → bleeding gums, poor healing, tooth mobility historically described—classic oral biochemistry–nutrition bridge (detail in 3.2).

Dentin organic matrix: odontoblasts secrete collagen-rich predentin that mineralizes. Non-collagenous proteins (e.g., dentin phosphoproteins/sialoproteins in broader teaching) regulate crystal placement—AFK level: collagen scaffold + controlled apatite deposition.

Periodontium: PDL collagen fiber bundles (principal fibers) embed as Sharpey fibers into cementum and alveolar bone. Chronic periodontitis involves host MMPs and bacterial proteases destroying this collagen architecture—biochemistry of attachment loss.

Enamel and Dentin Biochemistry

Hydroxyapatite chemistry

Tooth mineral is primarily hydroxyapatite, idealized as:

Ca₁₀(PO₄)₆(OH)₂

(Sometimes written Ca₅(PO₄)₃OH per formula unit.)

Biological apatite is carbonated and impure (substitutions with carbonate, Mg²⁺, Na⁺, F⁻, etc.), which affects solubility. Carbonate substitution generally increases solubility (more acid-vulnerable); fluoride substitution decreases solubility.

Demineralization–remineralization (D–R) balance:

• When oral fluid is undersaturated with respect to apatite (low pH, low Ca²⁺/PO₄), mineral dissolves
• When supersaturated at favorable pH with available Ca²⁺ and phosphate, ions redeposit (remineralization), especially with fluoride present
• Saliva supplies calcium, phosphate, and bicarbonate buffer—ties physiology (3.3 salivary) to biochemistry

Enamel matrix development (bridge to histology)

Ameloblasts secrete enamel matrix proteins (amelogenins, enamelins, ameloblastins in standard teaching). After mineralization, most protein is removed; mature enamel is protein-poor. Defects in matrix or maturation pathways contribute to amelogenesis imperfecta patterns—know the concept that organic matrix guides crystal growth then is largely lost.

Dentinogenesis: collagenous predentin → mineralized dentin; odontoblasts leave processes in tubules. Peritubular dentin is more mineralized than intertubular dentin—relevant to bonding and sensitivity physiology.

Fluoride Chemistry and Mineralization

Mechanisms of fluoride action

1. Systemic (developing teeth): F⁻ incorporates into forming apatite → fluorapatite Ca₁₀(PO₄)₆F₂ (or mixed fluorohydroxyapatite), more resistant to acid dissolution
2. Topical (erupted teeth—most important clinically): F⁻ adsorbs to crystal surfaces, promotes remineralization of early lesions, and forms a fluoridated surface layer; also has antimicrobial effects on plaque metabolism at sufficient concentrations
3. Critical pH effect: fluorapatite remains stable to lower pH than hydroxyapatite (often taught ~4.5 vs ~5.5), so fluoride-treated enamel tolerates acid challenges better

Fluoride does not “harden” teeth like metal tempering in a vague sense—it changes apatite chemistry and D–R kinetics. That wording precision wins AFK items.

Mineralization vs demineralization clinically

• Early caries: subsurface enamel demineralization with intact surface zone → white-spot lesion; still reversible if D–R balance restored
• Cavitation: surface collapses; restoration may be needed
• Root caries: cementum/dentin critical pH behavior and collagenous matrix make exposed roots vulnerable in older adults with recession

Integrating Biochemistry for AFK Stems

Practice connecting mechanisms:

1. Why does plaque sugar cause cavities? Bacterial fermentation → organic acids → local pH drop → apatite dissolution when undersaturated.
2. Why does fluoride help? Forms/stabilizes fluorapatite, favors remineralization, lowers effective critical pH for dissolution.
3. Why does scurvy affect gingiva? Collagen hydroxylation fails → fragile connective tissue and vessels.
4. Why is pulp sensitive to deep caries? Odontoblast/process injury plus inflammatory mediators; vital dentin is cellularly supported tissue, not inert mineral.
5. Why do MMPs matter after etching/bonding? Host enzymes can degrade exposed collagen in the hybrid layer, contributing to bond degradation over time.

AFK Study Checklist for This Section

• Trace glucose → pyruvate → acetyl-CoA → TCA → ETC → ATP; state net glycolytic ATP and role of O₂
• Define enzyme, cofactor, competitive inhibition; list three oral enzymes
• Sequence collagen synthesis and name the vitamin C step
• Recite enamel vs dentin % mineral/organic and the hydroxyapatite formula idea
• Explain fluorapatite, critical pH concept, and topical vs systemic fluoride roles

Master energy metabolism and matrix/mineral chemistry here; the next section maps vitamins and minerals onto the oral signs you will recognize in medicine and pathology stems.