Summary

Cell Membranes and Intracellular Membranes

• The matrix of a cell membrane or intracellular membrane consists of a bilayer of phospholipid molecules. The phospholipids are chemically very diverse, even within a single membrane, and in a particular cell the phospholipid composition can undergo change in response to environmental or other factors. The phospholipids are fluid, meaning that individual molecules move about relatively freely by diffusion within each membrane leaflet.
• Animals exhibit adaptive trends in the phospholipid compositions of their cell membranes. Cells that function routinely at low temperatures tend to have a phospholipid composition that permits membranes to remain fluid under cold conditions (e.g., they have high proportions of double bonds in the hydrocarbon tails).
• Five functional categories of proteins occur in cell and intracellular membranes: channels, transporters (carriers), enzymes, receptors, and structural proteins. A single protein may engage in more than one function.
• In addition to phospholipids and proteins, which are the principal components, membranes often have other components such as cholesterol (a lipid) and glycoproteins (composed of covalently bonded carbohydrate and protein subunits).

Epithelia

• An epithelium is a sheet of cells that lines a cavity or covers an organ or body surface, thereby forming a boundary between functionally different regions of the body or between the animal and the external environment.
• In a simple epithelium, each cell is fully encircled by a ring of tight or septate junctions formed with adjacent epithelial cells. These occluding-type junctions seal the spaces between adjacent cells. Moreover, the ring of junctions around each cell divides the cell membrane into chemically and functionally distinct apical and basolateral regions.
• An epithelium rests on a nonliving, permeable basement membrane secreted by the epithelial cells and underlying tissue. The apical membranes of metabolically active epithelial cells often bear a brush border of microvilli, greatly enhancing their surface area. In addition to the occluding junctions, adjacent epithelial cells are joined by structurally reinforcing “spot welds,” called desmosomes, and sometimes by gap junctions at which continuity is established between the cytoplasms of the cells.
• Materials pass through epithelia by paracellular paths between adjacent cells and by transcellular paths through cells. Materials traveling through a cell must pass through both the apical and the basolateral cell membranes of the cell.

Enzyme Fundamentals

• Enzymes are protein catalysts that accelerate reactions by lowering the activation energy required for reactants to reach transition state. For most reactions to occur in cells, they must be catalyzed by enzymes. Thus a cell controls which reactions occur within it by the enzymes it synthesizes.
• An enzyme must bind with its substrate to catalyze the reaction of substrate to form product. This binding, which is usually stabilized entirely by noncovalent bonds, occurs at a specific active site on the enzyme molecule, a site that is complementary in its three-dimensional chemical and electrochemical configuration to a portion of the substrate molecule. Enzyme molecules change shape when they bind to substrate or release product. These changes are permitted because the tertiary structure of a protein is stabilized by weak bonds.
• Enzyme properties that determine the velocity of an enzyme-catalyzed reaction in a cell are: (1) the number of active enzyme molecules present in the cell, (2) the catalytic effectiveness of each enzyme molecule when saturated, and (3) the enzyme–substrate affinity. Enzyme-catalyzed reactions exhibit saturation kinetics because the reaction velocity is limited by the availability of enzyme molecules at high substrate concentrations. The maximum reaction velocity (V_max) that prevails at saturation depends on properties 1 and 2: the amount and catalytic effectiveness of the enzyme. Property 3, the enzyme–substrate affinity, determines how closely the reaction velocity approaches V_max when (as is typical in cells) substrate concentrations are subsaturating. The enzyme–substrate affinity is measured by the half-saturation constant (i.e., the Michaelis constant, K_m, for enzymes displaying hyperbolic kinetics).
• Multisubunit enzymes often exhibit cooperativity, a phenomenon in which the binding of certain binding sites to their ligands affects (positively or negatively) the binding of other binding sites to their ligands. An important type of cooperativity is allosteric modulation, in which a nonsubstrate ligand called an allosteric modulator affects the catalytic activity of an enzyme by binding noncovalently with a specific regulatory (allosteric) binding site. Both allosteric activation and allosteric inhibition are possible.
• Enzymes catalyze reversible reactions in both directions because their action is to accelerate the approach toward reaction equilibrium (determined by principles of mass action), regardless of the direction of approach.
• Multiple molecular forms of enzymes occur at all levels of biological organization. Isozymes are multiple molecular forms within a single species. Interspecific enzyme homologs are homologous forms of an enzyme in different species. Functional differences between isozymes and interspecific enzyme homologs often prove to be adaptive to different circumstances.

Regulation of Cell Function by Enzymes

• The metabolic pathways active in a cell depend on which enzymes are present in the cell, as determined by the processes of enzyme synthesis (dependent on gene expression) and enzyme degradation. The presence or absence of enzymes in a cell is regulated on long and short timescales. During individual development (an example of a long timescale), tissues acquire tissue-specific patterns of gene expression that establish tissue-specific suites of enzymes and metabolic pathways. Inducible enzymes, such as the cytochrome P450 enzymes, exemplify shorter-term regulation of the presence or absence of enzymes and metabolic pathways.
• Very fast regulation of enzyme-catalyzed metabolic pathways is achieved by the modulation (upregulation or downregulation) of the catalytic activity of enzyme molecules already existing in a cell. Enzymes that catalyze rate-limiting or branch-point reactions are well positioned to mediate the rapid regulation of entire metabolic pathways in this way.
• Allosteric modulation and covalent modulation are the two principal types of modulation of existing enzyme molecules. Allosteric modulation occurs by way of the noncovalent binding of allosteric modulators to regulatory sites, governed by the principles of mass action. Covalent modulation requires the enzyme-catalyzed making and breaking of covalent bonds—most commonly with phosphate. Phosphorylation is catalyzed by enzyme-specific protein kinases, which usually are the principal controlling agents in covalent modulation.

Reception and Use of Signals by Cells

• Extracellular signals such as hormones initiate their actions on cells by binding noncovalently with specific receptor proteins. Receptor proteins activated by binding with their signal ligands set in motion cell signal transduction mechanisms that ultimately cause cell function to be altered.
• Most extracellular signaling molecules are chemically unable to enter cells because they are hydrophilic, or otherwise unable to pass through the hydrophobic, lipid interior of cell membranes. The receptors for these molecules are cell-membrane proteins that fall into three principal functional classes: ligand-gated channels, G protein–coupled receptors, and enzyme/enzyme-linked receptors. Extracellular signaling molecules that readily pass through cell membranes, such as steroid hormones, thyroid hormones, and nitric oxide (NO), bind with receptors that belong to a fourth functional class: intracellular receptors.
• Activation of ligand-gated channels by their ligands most commonly results in changed fluxes of inorganic ions, such as Na⁺ and K⁺, across cell membranes, thereby altering voltage differences across the membranes. The altered voltage differences may then trigger other effects.
• Activation of G protein–coupled receptors and enzyme/enzyme-linked receptors by their extracellular signaling ligands typically initiates the formation of second messengers, such as cyclic AMP or cyclic GMP, on the inside of the cell membrane. The second messengers, in turn, often trigger sequences of additional intracellular effects in which preexisting enzymes are modulated, most notably protein kinases. A function of these sequences is dramatic amplification of the ultimate effect.
• Intracellular receptors, when activated by their ligands, usually bind with nuclear DNA and directly activate specific primary-response genes.