Carbon Chemistry & Physiological Buffering —

Review of last lecture concepts

• pH, pKa, pKb, and buffering concepts: understanding how buffers resist pH change around their buffering ranges
• Carbonic acid ⇌ bicarbonate (HCO₃⁻) buffer as a major physiological buffer

Physiological buffering: the carbonic acid–bicarbonate system

• Key equilibrium: CO2 + H2O \rightleftharpoons H2CO3 \rightleftharrows H^+ + HCO_3^-
• Hydration of CO₂ forms carbonic acid (H₂CO₃); carbonic acid dissociates to bicarbonate and a proton
• pK_a values to remember:
• Carbonic acid (first dissociation): $pK_a \approx 3.8$
• Net buffering system for CO₂/HCO₃⁻ in body fluids: $pK_a^{net} \approx 6.2$
• Concept recap: when pH is around the pKa, the buffer is most effective; the ratio of conjugate base to acid shifts as pH moves away from pKa
• At a neutral pH (~7.0–7.4), the equilibrium is shifted toward bicarbonate (the conjugate base), making bicarbonate a relatively effective buffer near physiological pH
• Important takeaway: the buffering capacity against H⁺ is stronger near the pK_a values and weakens as pH moves far from them

Why the CO₂/bicarbonate system is physiologically important

• The system uses CO₂ produced by cellular metabolism and exhaled by the lungs as a way to regulate acidity
• CO₂ + H₂O forms carbonic acid, which can release H⁺, contributing to buffering
• The lungs provide a major route to remove CO₂, thereby helping regulate blood pH
• Conceptual takeaway: bicarbonate buffering ties together chemical equilibria with respiratory physiology

Real-world pH ranges and implications

• Stomach pH: $2 \sim 3$ (very acidic, aids protein hydrolysis in digestion)
• Blood (systemic) pH: typically around $7.35 \text{ to } 7.45$ (average ~7.4)
• Saliva pH: varies, often $6.4 \sim 7.2$; average around $6.8$; buffering in saliva helps protect teeth
• Enamel demineralization threshold: pH ≈ $5.5$; below this, enamel starts to dissolve
• Relationship to dentistry: lower salivary pH increases cavity risk; bicarbonate in saliva can diffuse into plaque to help buffer pH
• Nighttime saliva pH drops due to reduced breathing and CO₂ buildup in the mouth, which lowers pH and can promote cariogenic bacteria (e.g., lactobacilli, streptococci)
• Note on cariology: the buffering capacity of the carbonic acid–bicarbonate system helps counteract acidification, but extremes (low pH) still promote caries risk

Introduction to carbon chemistry (an overview for biochemistry)

• Carbon’s signature features: tetravalent, forms four bonds widely, enables diverse organic chemistry
• General example: methane, $CH_4$, with four single bonds to hydrogens (tetrahedral geometry)
• Chains and isomerism
• Linear/straight-chain alkanes: e.g., butane (C₄H₁₀)
• Branched isomers: e.g., isobutane (2-methylpropane), neopentane (2,2-dimethylpropane)
• For C₅H₁₂, isomers include n-pentane, isopentane (2-methylbutane), neopentane (2,2-dimethylpropane)
• Concept: isomers have the same molecular formula but different connectivity or arrangement
• Nomenclature basics
• Alkanes: saturated hydrocarbons ending in “-ane”; general formula $C<em>nH</em>{2n+2}$
• Alkenes: one or more carbon–carbon double bonds; general formula $C<em>nH</em>{2n}$; rotation about C=C is restricted (planar, no free rotation)
• Alkynes: triple bonds; general formula varies (noted as having two fewer hydrogens per multiple bond)
• Visualization and stereochemistry
• 2D representations (e.g., Fischer or wedge/dash) are shorthand for 3D geometry
• Tetrahedral carbon is the typical arrangement when a carbon forms four single bonds
• Rotation around C–C single bonds allows conformational flexibility (e.g., conformers around C–C in alkanes)
• Double bonds impose planarity and restrict rotation; cis/trans (E/Z) stereochemistry arises in alkenes with substituents on the double bond
• Aromatic systems
• Benzene ring: C₆H₆ with alternating double bonds, resonance, and delocalized π-electrons; historically described as aromatic due to stable ring systems and pleasant scent in many compounds
• Aromaticity arises from electron delocalization across the ring

Key chemical concepts that recur in biochemistry

• Oxidation states of carbon
• Defined loosely by how many oxygens are bonded to carbon and other heteroatoms
• Changes in oxidation state are common in metabolism, often enzyme-catalyzed in small-step transitions
• Functional groups (the reactive handles in biochemistry)
• Alcohols: functional group OH; general formula R–OH
• Aldehydes: carbonyl at the end of a carbon chain; R–CHO; typically ends with -al
• Ketones: carbonyl within the carbon chain; R–CO–R′; ends with -one
• Carboxylic acids: R–COOH; acidic proton; deprotonated form is carboxylate (R–COO⁻; ends with -oate when deprotonated)
• Amines: -NH₂ or -NH₃⁺; basic functional group; common in amino acids (R–NH₂ or R–NH₃⁺)
• Phosphate groups: phosphate-containing moieties common in energy biology (e.g., ATP) and phosphorylation
• Phenol: aromatic ring with single –OH substituent; e.g., tyrosine features a phenolic –OH
• Glycerol: 1,2,3-triol (propane-1,2,3-triol); important backbone in triglycerides and glycerophospholipids
• Carbohydrates and sugars
• Monosaccharides can be aldoses or ketoses
  • Glucose is an aldose (aldehyde group at the end of the chain)
  • Fructose is a keto sugar (ketone group within the chain)
• Sugars can exist in linear form or cyclize to form ring structures; equilibrium generally favors the cyclic form in solution
• Functional group focus: multiple hydroxyls (–OH) plus a carbonyl group (aldehyde or ketone)
• Amino acids and proteins
• Alpha amino acids: contain an amino group (–NH₂), a carboxyl group (–COOH), an alpha carbon, and a side chain (R group)
• The amino group and carboxyl group are attached to the same carbon (the alpha carbon); hence the term “alpha amino acid”
• The side chain (R group) determines identity and properties of the amino acid; there are 20 common amino acids used in biology
• Nomenclature and prefixes for hydrocarbons
• Linear prefixes: meth-, eth-, prop-, but-, pent-, hex-, hept-, oct-, non-, dec-
• Suffixes for hydrocarbon classes: -ane (alkane), -ene (alkene), -yne (alkyne)
• Branching nomenclature: isopentane (2-methylbutane) vs neopentane (2,2-dimethylpropane)
• The role of functional groups and isomerism in biochemistry
• Functional group isomerism: same molecular formula, different arrangement, leading to different functional groups (e.g., dimethyl ether vs dimethyl alcohol)
• Structural isomerism (constitutional isomers) vs stereoisomerism (cis/trans around double bonds, chiral centers)

Practical exam-oriented points

• Given several C and H compounds, identify which are isomers of each other by checking the connectivity and counts
• Recognize functional group names by suffixes and their typical reactivity (e.g., aldehydes end in -al, ketones in -one, carboxylic acids in -ic acid or -ate when deprotonated)
• Distinguish between alkanes, alkenes, and alkynes by presence of single, double, or triple bonds and note rotation restrictions for double bonds
• Identify cis/trans (E/Z) isomerism in alkenes when two different substituents are attached to the double bond
• Understand the quiz/test expectation: you’ll encounter typical examples of hydrocarbons, functional groups, and basic biomolecules; be ready to name, classify, or compare

Connections to broader biology and metabolism

• Biochemical pathways often proceed in small, enzyme-mediated steps, frequently altering oxidation state and functional group chemistry to move substrates through metabolic routes
• Lipids and fatty acids involve beta (β) nomenclature in chain oxidation and metabolism, with alpha (α), beta (β), gamma (γ), delta (δ) designations used to describe positions along carbon chains
• Fatty acids and related oxidation states are central to understanding energy production and lipid metabolism in subsequent lectures

Quick reference formulas and terms

• Carbonic acid hydration and buffering: CO2 + H2O \rightleftharpoons H2CO3 \rightleftharrows H^+ + HCO_3^-
• pK_a references:
• $pK<em>a(H</em>2CO_3) \approx 3.8$
• $pK<em>a^{net} (CO</em>2/ HCO_3^-) \approx 6.2$
• Buffer action around pH 7: bicarbonate predominates over carbonic acid when pH > pK_a(H₂CO₃)
• Biological pH values to remember:
• Gastric pH: $2 \sim 3$
• Saliva pH: $6.4 \sim 7.2$ (avg ≈ $6.8$)
• Blood pH: $7.35 \sim 7.45$ (avg ~7.4)
• Enamel demineralization threshold: $pH \approx 5.5$
• Common hydrocarbon formulas:
• Alkanes: $C<em>nH</em>{2n+2}$
• Alkenes: $C<em>nH</em>{2n}$ (double bond, no rotation around C=C)
• Structural concepts:
• Tetrahedral carbon typically forms four bonds; rotation around C–C single bonds; double bonds are planar and restrict rotation
• Aromatic benzene: ring with delocalized π-electrons; aromatic stability and property implications
• Functional groups (suffixes/prefixes):
• Alcohol: OH (R–OH)
• Aldehyde: suffix -al (R–CHO)
• Ketone: suffix -one (R–CO–R′)
• Carboxylic acid: suffix -ic acid or -ate when deprotonated (R–COOH or R–COO⁻)
• Amine: –NH₂ or –NH₃⁺
• Phosphate group: P–O bonds (phosphate esters, phosphorylation)
• Phenol: benzene ring with –OH substituent (e.g., tyrosine contains phenolic –OH)
• Sugar chemistry basics:
• Glucose: an aldehyde sugar (aldose)
• Fructose: a ketose
• Ring vs linear forms; ring forms predominate in solution
• Amino acids:
• Alpha amino acids: α-carbon bearing –NH₂ and –COOH groups, plus side chain R
• Twenty common amino acids with diverse R groups

Note on terminology and language used in biochemistry discussions

• Terms like alpha, beta, gamma, delta are used to describe positions along carbon chains (e.g., in fatty acids) and play a crucial role in oxidation pathways such as beta-oxidation
• The discussion ties core organic chemistry principles to their biological applications in metabolism, physiology, and biochemistry

Summary takeaway

• The carbonic acid–bicarbonate buffer is central to physiological pH regulation, linking chemistry to respiratory physiology
• Carbon chemistry concepts (bonding, geometry, isomerism, functional groups) form the foundation for understanding biomolecules (carbohydrates, lipids, amino acids) and metabolic pathways
• Mastery of these concepts prepares you for predicting reactivity, naming compounds, and understanding biochemical pathways in subsequent lectures