Chapter Notes: Introduction to the Chemistry of Life

Atoms, molecules and compounds

Learning outcomes

• Define the following terms: atomic number, atomic weight, isotope, molecular weight, ion, electrolyte, pH, acid and alkali.
• Describe the structure of an atom.
• Discuss the types of bond that hold molecules together.
• Outline the concept of molar concentration.
• Explain the importance of buffers in the regulation of pH.

All matter is made of particles called atoms. An element contains only one type of atom (for example, carbon, hydrogen or oxygen). Substances containing two or more different atoms chemically combined are called compounds (for example, water, H₂O). Although there are many naturally occurring elements, the chemical composition of living tissues is dominated by carbon, hydrogen, oxygen and nitrogen; smaller but important amounts of sodium, potassium, calcium and phosphorus are also present.

Atomic structure

Atoms consist of a tiny central nucleus of protons and neutrons surrounded by electrons occupying energy levels (often represented as shells). Protons carry a positive electric charge, electrons a negative charge, and neutrons are electrically neutral. In a neutral atom the number of protons equals the number of electrons, so there is no net charge.

Electrons occupy discrete energy levels around the nucleus. The maximum number of electrons in the first four shells is 2, 8, 18 and 32 respectively. Electrons in the outermost shell (valence electrons) determine an atom's chemical reactivity: atoms with incomplete outer shells tend to gain, lose or share electrons to reach a stable configuration.

Atomic number and atomic weight

The atomic number of an element is the number of protons in the nucleus and uniquely identifies the element. For example, hydrogen has atomic number 1, oxygen 8 and sodium 11. The atomic weight (more precisely, relative atomic mass) of an atom is the sum of the numbers of protons and neutrons in its nucleus (that is, the mass of the nucleus in atomic mass units). Because naturally occurring elements are mixtures of isotopes, tabulated atomic weights are averages weighted by isotopic abundance.

Isotopes

Isotopes are atoms of the same element that differ in neutron number and therefore in atomic mass. Isotopes have the same chemical behaviour (same proton and electron numbers) but different masses. Examples of hydrogen isotopes are:

• Protium (most common): 1 proton, 0 neutrons.
• Deuterium: 1 proton, 1 neutron.
• Tritium: 1 proton, 2 neutrons.

Because isotopes differ in mass, average atomic weights (as quoted in tables) are fractional values (for example, hydrogen ≈ 1.008; chlorine ≈ 35.5 because of a mixture of 35Cl and 37Cl isotopes).

Molecules and compounds

A molecule is two or more atoms chemically bonded. If the atoms are of different elements the molecule is also a compound. Compounds containing carbon and hydrogen are generally called organic; most biological macromolecules are organic, while many other important substances (salts, acids, bases) are inorganic.

Covalent and ionic bonds

Chemical bonds between atoms are mainly of two kinds in biological chemistry:

• Covalent bonds - atoms share one or more pairs of electrons. Covalent bonds are strong and form the backbone of most biological molecules. Example: in a water molecule each hydrogen atom shares an electron pair with oxygen so that oxygen attains an octet (eight electrons) in its outer shell while each hydrogen attains a duet (two electrons).
• Ionic bonds - one atom transfers an electron to another, producing oppositely charged ions that attract each other. Example: when sodium (Na) transfers an electron to chlorine (Cl), sodium becomes Na⁺ and chloride becomes Cl^-; the electrostatic attraction between Na⁺ and Cl^- yields sodium chloride (table salt).

Electrolytes

An electrolyte is a substance that dissociates into ions when dissolved in water and therefore conducts electricity. Electrolytes are essential for:

• conducting electrical impulses for nerve and muscle function;
• exerting osmotic effects that help distribute water between body compartments;
• acting as chemical buffers that resist changes in pH.

Measurement of substances in body fluids

Concentrations in body fluids may be expressed in units of mass (mg, µg), molar concentration (mol·L^-1, mmol·L^-1), or as milliequivalents per litre (mEq·L^-1) when ionic charge is important. Some hormones and biologicals are measured by activity units (for example, international units, IU).

Acids, bases and pH

Hydrogen ion concentration and the pH scale

The acidity or alkalinity of a solution is determined by its hydrogen ion concentration, [H⁺], and is expressed on the pH scale, which ranges from 0 to 14 with pH 7 as neutral (pure water). pH < 7="" is="" acidic="" (higher="">⁺]) and pH > 7 is alkaline (lower [H⁺]). Each unit change in pH represents a tenfold change in hydrogen ion concentration (for example, pH 5 has ten times more H⁺ than pH 6).

Acids, bases and salts

An acid donates H⁺ in solution. A base accepts H⁺, often releasing OH^-. A salt yields other cations and anions when dissolved (for example, NaCl yields Na⁺ and Cl^-).

Strong and weak acids/bases

Strong acids (for example, hydrochloric acid, HCl) dissociate almost completely into H⁺ and their anions. Weak acids (for example, carbonic acid, H₂CO₃) dissociate only partially; hence [H⁺] measures the dissociated (ionised) portion rather than total acid present. Similarly, bases may be strong or weak according to their degree of dissociation.

pH of body fluids

Most body fluids are close to neutral because physiological processes require tightly controlled pH ranges. Saliva ranges about pH 5.4-7.5 (optimum for salivary amylase), gastric juice is highly acidic to aid digestion and to destroy pathogens, and blood is maintained at pH ≈ 7.35-7.45. Small deviations outside these ranges can disrupt biochemical reactions and organ function.

Buffers

A buffer is a system that minimises pH change when acid or base is added. The main physiological buffer systems are:

• Bicarbonate buffer: CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃^-. The lungs and kidneys cooperate with this buffer: the lungs control CO₂ (thus shifting the equilibrium) and the kidneys adjust bicarbonate and H⁺ excretion.
• Protein buffers: proteins (including haemoglobin) can bind or release H⁺, buffering both plasma and intracellular fluid.
• Phosphate buffer: important inside cells, where HPO₄^2-/H₂PO₄^- pairs resist pH change.

The lungs rapidly regulate pH by altering ventilation rate to change CO₂ elimination. The kidneys regulate pH more slowly by changing H⁺ and HCO₃^- excretion and by generating new bicarbonate, for example through ammonium production.

Acidosis and alkalosis

If blood pH falls below ≈ 7.35 the condition is called acidosis; if it rises above ≈ 7.45 the condition is alkalosis. Both states impair cellular and organ function. Common causes of acidosis include respiratory retention of CO₂ (respiratory acidosis), increased production of metabolic acids (for example, diabetic ketoacidosis) or reduced renal acid excretion. Alkalosis may follow excessive loss of acid (for example, vomiting), excessive bicarbonate retention, or hyperventilation (respiratory alkalosis).

Important biological molecules

Learning outcomes

• Describe the chemical nature of sugars, proteins, lipids, nucleotides and enzymes in simple terms.
• Discuss the biological importance of each group.

Carbohydrates

Carbohydrates are compounds of carbon, hydrogen and oxygen, commonly arranged with the formula C_n(H₂O)_n. Monosaccharides (simple sugars) such as glucose and fructose are single-ring units. Two monosaccharides join by a glycosidic bond with the loss of one water molecule to form disaccharides (for example, sucrose). Long chains of monosaccharides form polysaccharides (for example, starch and glycogen).

Glucose is the preferred fuel of many cells. It may be metabolised aerobically (with O₂) or anaerobically; aerobic metabolism yields much more energy (ATP) per glucose molecule. Functions of carbohydrates include:

• providing a rapid source of metabolic energy;
• serving as storage forms of energy (glycogen in animals);
• forming part of nucleic acid structure (ribose/deoxyribose in RNA/DNA);
• acting as recognition structures on cell surfaces (glycoproteins and glycolipids).

Amino acids and proteins

Amino acids contain an amino group (-NH₂), a carboxyl group (-COOH), a hydrogen and a variable side chain (R group) attached to a central carbon. Twenty principal amino acids are used to build human proteins. Two amino acids join by a condensation reaction that forms a peptide bond and releases one molecule of water. Chains of amino acids are polypeptides; when folded into specific three-dimensional shapes they become functional proteins.

Protein structure and function are closely linked. Many proteins act as:

• transport molecules (for example, haemoglobin);
• enzymes (biological catalysts);
• hormones (for example, insulin);
• antibodies (immune defence).

Changes in pH or temperature may disrupt the internal bonds stabilising a protein's three-dimensional shape (denaturation), often abolishing its function.

Lipids

Lipids are a broad class of hydrophobic molecules mainly composed of carbon, hydrogen and oxygen; many also contain phosphorus or nitrogen. Major lipid classes important in physiology include:

• Triglycerides (fats) - glycerol esterified with three fatty acids; stored in adipose tissue and used for long-term energy storage and insulation.
• Phospholipids - amphipathic molecules forming the bilayer of cell membranes, with hydrophilic heads and hydrophobic tails.
• Steroids - for example, cholesterol (which stabilises membranes) and steroid hormones produced by adrenal and gonadal tissues.
• Prostaglandins and related eicosanoids - lipid mediators derived from fatty acids involved in inflammation and other signalling processes.

Fatty acids may be saturated (no double bonds) or unsaturated (one or more double bonds); saturation affects physical state (solid versus liquid) and biological effects.

Nucleotides and nucleic acids

Nucleotides are compounds composed of a pentose sugar (ribose or deoxyribose), a nitrogenous base (for example, adenine) and one or more phosphate groups. Nucleotides are the building blocks of nucleic acids: DNA (deoxyribonucleic acid) and RNA (ribonucleic acid), which store and transfer genetic information.

Adenosine triphosphate (ATP)

ATP (adenosine triphosphate) is a nucleotide formed from adenine, ribose and three phosphate groups. ATP is the principal energy currency of the cell. Energy released by the breakdown of nutrients is used to synthesize ATP from ADP (adenosine diphosphate) and inorganic phosphate. When ATP is hydrolysed back to ADP and phosphate, energy is released to drive cellular processes such as muscle contraction, membrane transport and biosynthesis.

Enzymes

Enzymes are proteins that catalyse biochemical reactions, increasing reaction rates without being consumed. Each enzyme recognises specific substrate(s) that bind at the enzyme's active site. The enzyme stabilises transition states and lowers activation energy so the reaction proceeds rapidly. After the reaction, the product is released and the enzyme is available for another cycle.

Enzymes are sensitive to environmental conditions: temperature and pH influence activity and can denature enzymes if extremes occur. Many enzymes require cofactors (metal ions or small organic molecules, sometimes derived from vitamins) for activity. Enzymes that assemble molecules are often involved in anabolic reactions; enzymes that break molecules down participate in catabolic reactions. Most enzyme names end with the suffix -ase.

Movement of substances within body fluids

Learning outcomes

• Compare and contrast the processes of diffusion and osmosis.
• Describe how molecules move within and between body compartments using these concepts.

Transport of substances within and between body fluids - and across cell membranes - is essential for physiology. Movement can be passive (no metabolic energy required) or active (energy required, usually supplied by ATP).

Diffusion

Diffusion is the net movement of solute molecules from an area of higher concentration to an area of lower concentration down their concentration gradient, until equilibrium is reached. Diffusion occurs in gases, liquids and solutions and is faster at higher temperatures and with steeper concentration gradients. Across biological membranes, only molecules small enough or lipid-soluble can diffuse freely (for example, O₂ and CO₂ diffuse across alveolar and capillary membranes; large proteins generally cannot).

Osmosis and tonicity

Osmosis is diffusion of water across a semipermeable membrane from a region of lower solute concentration (higher water concentration) to a region of higher solute concentration (lower water concentration). The driving force is the osmotic pressure generated by impermeant solutes.

Tonicity describes the effect of an external solution on a cell:

• Isotonic - external solution has the same effective osmolarity as the cell interior; no net water movement and cell volume remains stable.
• Hypotonic - external solution is more dilute (lower osmolarity) than the cell interior; water enters the cell and it may swell or burst (lysis).
• Hypertonic - external solution is more concentrated (higher osmolarity) than the cell interior; water leaves the cell and it shrinks (crenation).

Body fluids

Learning outcomes

• Define intracellular fluid and extracellular fluid.
• Explain, with examples, why homeostatic control of the composition of these fluids is vital to body function.

Approximately 60% of an average adult's body mass is water (about 40 L in a 70 kg adult). This fraction is higher in infants and lower in the elderly and in obesity. Body water is distributed between two main compartments:

• Intracellular fluid (ICF) - fluid inside cells; about 70% of total body water (~28 L in a 70 kg adult).
• Extracellular fluid (ECF) - fluid outside cells; about 30% of total body water (~12 L), which includes interstitial fluid bathing tissues and plasma (the liquid portion of blood).

Extracellular fluid

The extracellular fluid comprises plasma, lymph, cerebrospinal fluid, interstitial (tissue) fluid and small specialised fluids (synovial, pleural, pericardial). Interstitial fluid bathes most cells and is the medium for exchange of gases, nutrients and wastes between blood and cells. The composition of ECF must be tightly regulated: for example, small changes in plasma potassium or sodium concentrations can cause muscle weakness, cardiac arrhythmias or neurological symptoms.

Intracellular fluid

The composition of the intracellular fluid differs significantly from ECF. For example, sodium concentration is much higher in the ECF than in the ICF, whereas potassium concentration is higher inside cells than outside. This ionic distribution is actively maintained by membrane transport mechanisms (for example, the sodium-potassium pump, Na⁺/K⁺-ATPase). Water moves freely across most cell membranes, so changes in ECF osmolarity produce rapid changes in cell water content and volume.

Homeostatic mechanisms - including hormonal control, renal function and respiratory regulation - continually adjust the composition and volume of body fluids to support normal cellular and organ function.