Functions and general structure of biological membranes
Biological membranes perform several key tasks: they separate the cell contents from the external environment, regulate substance transport, form intercellular junctions, and ensure the perception of external signals. The structural basis of the membrane is a double lipid bilayer formed by amphiphilic molecules. Lipids and proteins are held in the membrane by non-covalent (weak) bonds, which provides fluidity and plasticity to the structure.
The amphiphilicity of phospholipids is determined by the presence of a polar (hydrophilic) head and two non-polar (hydrophobic) tails. The tails face each other inside the bilayer, while the heads face outward and toward the cytoplasm.
Lipid composition of membranes
The main classes of membrane lipids are phospholipids, glycolipids, and cholesterol.
- Cholesterol regulates membrane stiffness and fluidity: its deficiency makes the membrane too fluid, while its excess makes it too rigid.
- Phospholipids are built from a glycerol residue, two fatty acid residues, a phosphate group, and a polar group. Based on the nature of the polar group, phosphatidylserine, phosphatidylethanolamine, phosphatidylcholine, and phosphatidylinositol are distinguished. Cardiolipins are part of mitochondrial membranes.
- Sphingolipids are derivatives of sphingosine. They include ceramides (sphingosine + fatty acid), cerebrosides (ceramide + monosaccharide, usually galactose), and sphingomyelins (sphingosine, fatty acid, phosphate, choline). Cerebrosides and sphingomyelins are characteristic of nerve tissue membranes.
During complete hydrolysis of a phospholipid, ester bonds are broken: for example, sphingomyelin yields sphingosine, fatty acid, phosphoric acid, and choline; phosphatidylcholine yields glycerol, two fatty acids, phosphate, and choline.
Membrane proteins and substance transport
Proteins are divided into integral (transmembrane) proteins, which span the bilayer, and peripheral proteins, facing the cytoplasm or extracellular environment. Membrane proteins are often glycosylated and phosphorylated, which protects them from proteases. They act as receptors, enzymes, and transporters, participate in immune responses, and form intercellular junctions.
Transport across the membrane can be passive or active:
- Simple diffusion — for lipophilic substances (steroid hormones) moving freely through the bilayer along the concentration gradient.
- Facilitated diffusion — for hydrophilic substances via a carrier protein, also along the gradient.
- Primary active transport — against the concentration gradient with direct ATP expenditure (e.g., Na⁺/K⁺-ATPase).
- Secondary active transport — symport or antiport utilizing the Na⁺ gradient created by the ATPase (e.g., glucose uptake coupled with sodium).
Adenylate cyclase and inositol phosphate systems
Signaling molecules (primary messengers) include hormones, neurotransmitters, growth factors, and eicosanoids. Receptors are divided into membrane receptors (ionotropic and metabotropic) and intracellular receptors. Metabotropic receptors include G protein-coupled receptors and catalytic receptors.
In the adenylate cyclase system (glucagon, epinephrine via β-adrenergic receptors), the hormone changes the conformation of the receptor, which is transmitted to the α-subunit of the G protein. GDP is replaced by GTP, and the α-subunit activates adenylate cyclase, which converts ATP into cAMP. cAMP activates protein kinase A by dissociating its regulatory subunits; the catalytic subunits phosphorylate regulatory enzymes. Degradation enzymes are active in the phosphorylated state, while synthesis enzymes are inactive. cAMP is degraded by phosphodiesterase. Cholera toxin blocks the dephosphorylation of GTP by the α-subunit, causing continuous activation of adenylate cyclase and accumulation of cAMP. Via the Gi protein, the α-subunit conversely inhibits the enzyme.
In the inositol phosphate system (ADH, epinephrine via α₁-receptors), phospholipase C is activated, cleaving phosphatidylinositol 4,5-bisphosphate into inositol 3-phosphate (IP₃) and diacylglycerol (DAG). IP₃ binds to ryanodine receptors on the endoplasmic reticulum, releasing Ca²⁺. Calcium ions together with DAG activate protein kinase C and bind to calmodulin, triggering a cellular response.
Catalytic and intracellular receptors
Insulin receptor is a tyrosine protein kinase composed of two α- and two β-subunits. Upon insulin binding, β-subunits undergo autophosphorylation at tyrosine residues and phosphorylate IRS protein (Insulin Receptor Substrate). IRS activates phosphoprotein phosphatase, phosphodiesterase, and transcription factors, and promotes GLUT-4 insertion into the membrane of adipocytes and myocytes. The ultimate effect of insulin action is dephosphorylation of regulatory enzymes: synthetic enzymes are activated, while degradative enzymes are inactivated.
The guanylate cyclase receptor (atrial natriuretic peptide, guanylin) synthesizes cGMP from GTP by itself. cGMP activates protein kinase G by binding to its subunits without dissociation; protein kinase G phosphorylates regulatory enzymes.
Intracellular receptors include cytoplasmic (for steroid hormones) and nuclear receptors (for iodothyronines T₃, T₄). Hydrophobic hormones pass through the membrane by diffusion, forming a hormone-receptor complex that binds to DNA and regulates transcription. This mechanism is called enzyme synthesis induction and alters the quantity rather than the activity of proteins.
Key points
- The membrane is a lipid bilayer composed of amphiphilic phospholipids with incorporated cholesterol and proteins.
- Cholesterol maintains optimal membrane fluidity.
- Substance transport is divided into passive (simple and facilitated diffusion) and active (primary and secondary).
- The adenylate cyclase system (glucagon, epinephrine) increases cAMP and activates protein kinase A, phosphorylating enzymes.
- The inositol phosphate system, via IP₃ and DAG, increases Ca²⁺ levels and activates protein kinase C.
- Cholera toxin blocks the GTPase activity of the αs-subunit, causing persistent activation of adenylate cyclase.
- The insulin receptor is a tyrosine kinase, and its ultimate effect is the dephosphorylation of regulatory enzymes.
- Steroid hormones and iodothyronines act via intracellular receptors, regulating gene transcription.