Prokaryotic Metabolism of Sugars

Caries (definition)

Progressive destruction of mineralized tooth tissues (enamel, dentin, or cementum) initiated by microbial activity on fermentable dietary carbohydrates at the tooth surface.

Classic caries triad (Agent-Host-Environment)

Caries requires the overlap of Agent, Host, and Environment.

Caries triad, restated for the mouth

Caries results from the overlap of cariogenic bacteria (in dental plaque), a substrate (fermentable carbohydrate), and a susceptible tooth surface.

Why does carbohydrate structure matter for caries?

Carbohydrate structure determines whether a given sugar is fermentable by oral bacteria.

Why do carbohydrates dominate (over protein/fat) in caries formation?

Carbohydrates act as the direct fuel source for oral bacteria, which ferment them into acids that dissolve tooth enamel — unlike proteins and fats.

Digestion in the oral cavity

Little digestion occurs in the mouth; it is not the main site of nutrient breakdown, though carbohydrate digestion (via salivary amylase) is an exception that starts there.

Where does most digestion occur?

The majority of digestion happens in the lower digestive system — the small and large intestine.

Average American diet — macronutrient breakdown (by calories)

Roughly 60% carbohydrate, 24% fat, 16% protein.

Nutrients absorbed directly without digestion

Water, inorganic salts, vitamins, and certain lipids.

Digestion (definition)

The hydrolysis of complex foodstuffs (proteins, carbohydrates, and lipids) into simpler components.

Absorption (definition)

The process by which products of digestion are transported from the intestinal lumen into intestinal epithelial cells (and ultimately into the circulatory system).

What determines which microbes colonize different parts of the digestive system?

The availability of fermentable nutrients in that region.

Saliva — pH and key functions

Close to neutral pH (6.4-7.3); moistens food (largely via mucins, glycoproteins ~60% carbohydrate by weight and very viscous) and contains amylase to begin starch/glycogen digestion.

Salivary amylase

Initiates hydrolysis of glycogen and starches by catalyzing hydrolysis of alpha-1,4 glycosidic bonds.

Why are simple carbohydrates especially cariogenic?

Simple carbohydrates (glucose, fructose, sucrose, lactose) can be directly absorbed/used by bacteria in the mouth, unlike complex carbohydrates that first require breakdown.

Role of salivary amylase in caries formation

It releases mono- and disaccharides from complex polysaccharides (starch and glycogen), making more fermentable sugar available to oral bacteria.

Why is sucrose particularly detrimental to dental health?

Sucrose is used by bacteria to synthesize exopolysaccharides, a key component of dental biofilms/plaque; higher sucrose intake correlates with more tooth decay.

S. mutans genome and carbohydrate metabolism

Genes involved in carbohydrate metabolism constitute a significant portion of the S. mutans genome, reflecting how central sugar handling is to this organism.

Glucosyltransferases (gtfB, gtfC, gtfD)

Convert n Sucrose → Glucan (glucose)n + n Fructose; the glucan produced is required for dental biofilm formation.

Fructosyltransferase (ftf)

Converts n Sucrose → Fructan (fructose)n + n Glucose.

Fructosidase (fruA)

Converts Fructan (fructose)n → n Fructose, releasing free fructose.

Purpose of secreted ftf and fruA enzymes

S. mutans may use them to store carbohydrates (as fructan) within the biofilm for later use.

Simple diffusion (nutrient transport)

Movement down a concentration gradient; requires neither a membrane transporter nor a source of energy.

Facilitated transport

Movement down a concentration gradient; requires a membrane transporter but not a source of energy.

Active transport

Movement against a concentration gradient; requires both a membrane transporter and a source of energy (e.g., ATP, PEP, or an ion gradient).

Do carbohydrates get absorbed by simple diffusion?

No — no carbohydrates are absorbed by simple diffusion.

Sugar Phosphotransferase System (PTS)

An active transport mechanism in S. mutans that couples sugar translocation with phosphorylation, transferring a phosphoryl group from phosphoenolpyruvate (PEP) through a relay (EI, HPr, EIIA, EIIB, EIIC) onto the sugar as it crosses the membrane.

ABC (ATP-binding cassette) transporters

Membrane transport systems that use ATP hydrolysis (via ATPases) to actively move sugars across the membrane.

Catabolic processes

Breakdown reactions that capture 'energy' in biochemical intermediates/carriers from fuel molecules (e.g., glucose).

Anabolic processes

Synthesis reactions that expend 'energy' from biochemical intermediates/carriers to build macromolecules (DNA, RNA, proteins, glycosaminoglycans, lipids).

ATP (basic role)

The universal short-term storage form of chemical energy in biology; consists of adenosine plus three phosphoryl groups.

Energetics of ATP synthesis vs. hydrolysis

ATP synthesis (ADP + Pi → ATP + H2O) requires significant free energy (ΔG°′ = +7.3 kcal/mol); ATP hydrolysis (ATP + H2O → ADP + Pi) yields significant free energy (ΔG°′ = −7.3 kcal/mol).

Redox (reduction-oxidation) reaction

A reaction involving a net transfer of electrons from one chemical species to another.

Reductant vs. Oxidant

Reductant = species that gives up electrons; Oxidant = species that takes up electrons. Oxidant + Reductant → reduced Oxidant + oxidized Reductant.

Mnemonic for oxidation/reduction

OIL RIG — Oxidation Is Loss (of electrons), Reduction Is Gain (of electrons).

Pyridine nucleotides

NAD+/NADH and NADP+/NADPH — electron carriers whose oxidized (NAD+) and reduced (NADH) forms differ by addition of H+ and 2 electrons from a substrate.

Difference between NAD+ and NADP+

NADP+ has an extra phosphate group on the ribose compared to NAD+; this difference determines which enzymes/pathways use NAD+ versus NADP+ (distinct roles in metabolism).

Overview: 4 stages from glucose to ATP (aerobic)

1) Glycolysis converts glucose to 2 pyruvate. 2) Pyruvate dehydrogenase complex converts pyruvate to Acetyl-CoA. 3) The Citric Acid Cycle oxidizes the acetyl group to CO2, generating NADH. 4) The Electron Transport Chain and Oxidative Phosphorylation pass electrons from NADH to oxygen to synthesize ATP.

Anaerobic glycolysis — net reaction

Glucose + 2 ADP + 2 Pi → 2 lactate + 2 ATP (ΔG°′ for hydrolysis of the ATP produced = 2 × −7.3 = −14.6 kcal/mol).

Complete oxidation of glucose — net reaction

Glucose + 6 O2 → 6 CO2 + 6 H2O, ΔG°′ = −686 kcal/mol.

Why does anaerobic glycolysis produce lactate?

Without oxidative phosphorylation, cells must regenerate NAD+ some other way; lactate dehydrogenase reduces pyruvate to lactate, which restores the NAD+ needed to keep glycolysis running (and lactate is excreted as lactic acid).

Phosphoglucoisomerase reaction

Interconverts glucose-6-phosphate and fructose-6-phosphate; it is reversible (ΔG°′ close to 0), so F-6-P is not irreversibly committed to the glycolytic pathway at this step.

Phosphofructokinase (PFK) reaction

Converts fructose-6-phosphate + ATP → fructose-1,6-bisphosphate + ADP + H+; this is the irreversible 'commitment' step of glycolysis.

PFK regulation

Stimulated allosterically by AMP and ADP; inhibited by ATP and citrate.

Pyruvate kinase reaction

Converts phosphoenolpyruvate (PEP) + ADP → pyruvate + ATP; irreversible (ΔG°′ = −7.5 kcal/mol), thermodynamically pulling the reactions from F-1,6-bisP to pyruvate forward.

Pyruvate kinase regulation

Activated by AMP, ADP, and fructose-1,6-bisphosphate; inhibited by ATP.

Common regulatory logic across PFK and pyruvate kinase

Both are activated by low-energy signals (AMP/ADP) and inhibited by high-energy signals (ATP), coupling glycolytic flux to the cell's energy state.