Test Questions

1. List the basic cell membrane structures.

2. What is the qualitative and quantitative composition of membranes?

3. What lipids are parts of biological membranes? What are their properties and functions?

4. What is the difference between peripheral and integral proteins of biological membranes?

5. What factors can cause changes in the structure and permeability of the membrane?

6. List types of substances transport through the membrane. Which of them require an expenditure of energy?

7. What is the role of ATP-ase in the functioning of biological membranes?

5. Transmembrane transduction of the hormonal signal

Hormones are substances of organic nature, which are produced in the specialized cells of the endocrine glands, enter into the bloodstream and have a regulating effect on the metabolism and physiological functions. The specific characteristics of the biological action of hormones: hormones exert their biological effects in very small concentrations (from 10^-6 to 10^-12 M); the hormonal effect is realized through protein receptors and intracellular second messengers; hormones increase the rate of enzyme synthesis de novo or change the velosity of enzymatic catalysis; the hormones effect in the whole organism is determined to some extent by controlling influence of the CNS.

Modern classification of hormones is based on their chemical nature.

1. Peptide and protein hormones include from 3 to 250 or more amino acid residues, for example, hormone of the hypothalamus and pituitary gland (growth hormone, corticotropin and others), and pancreatic hormones (insulin, glucagon).

2. Amino acid derivatives. These are adrenaline and thyroid hormones.

Hormones of these two groups are highly soluble in water.

3. Steroid hormones. All of them are formed from cholesterol. These are corticosteroids, sex hormones (estrogens and androgens), hormonal form of vitamin D. Steroid hormones are lipophilic substances, easily penetrating the cell membrane.

4. Eicosanoids are hormone-like substances that have a local effect. They are derived from polyunsaturated fatty acid – arachidonic acid.

Cell membranes due to the presence of specific receptors receive signals from the environment (for example, molecules of hormones, called primary messengers or intermediaries). The first stage of the hormone action on the target cell is its binding to the receptor, and then the signal is transmitted into the cell. By its chemical nature, almost all the receptors of biologically active substances are glycoproteins. A common property of all receptors is their high specificity towards one specific hormone.

Adenylatecyclase messenger system is the most studied system(Fig. 17). It involves: 1) hormone receptor, and 2) the enzyme adenylyl cyclase, and 3) G- protein, and 4) cAMP -dependent protein kinase 5) phosphodiesterase.

Fig. 17. Adenylatecyclase messenger system.

The molecules of the protein hormones (insulin), hydrophilic molecules (adrenaline) cannot pass through the cell membrane. Their receptors are located on the membrane. Binding of hormone (the primary messenger) to the receptor leads to structural changes in the receptor intracellular domain. It provides interaction of the receptor with GTP-binding protein (G-protein). G-protein is a mixture of two types of proteins: active G_s (from the Eng. stimulatory) and inhibitory G_i. They have three different subunits (α, β and γ). The function of G-protein is carrying out a hormonal signal at the plasma membrane. Hormone-receptor complex transforms G_s-protein in the activated state. It is activated by dissotiation of G-protein subunits. The active G-protein activates adenylate cyclase. Adenylate cyclase is almost inactive in the absence of G-protein.

Adenylate cyclase is an integral plasma membrane protein and its active site is oriented toward the cytoplasm. Adenylate cyclase catalyzes the reaction of synthesis of cAMP from ATP. cAMP is a second messenger.

Under the action of cAMP inactive protein kinase turnes into active form. This enzyme catalyzes the phosphorylation of intracellular enzymes or target proteins, changing their activity. This reaction goes with the participation of serine, threonine, tyrosine OH-groups. Phosphorylation and dephosphorylation of proteins with the participation of protein kinases is a common fundamental mechanism of secondary messengers within the cell.

Phosphodiesterase causes the breakdown of cAMP and thereby terminates the hormonal signal.

Steroid and thyroid hormones are lipophilic and can easily pass through cell membranes. The receptors of these substances are in the cytosol or nucleus of the cell (intracellular receptors).

Complex of hormone with a receptor is formed in the cytosol, and then enters the nucleus. Hormone-receptor complex passes into the nucleus and interacts with a regulatory nucleotide sequence in DNA. Accordingly, the rate of transcription of structural genes and the rate of translation are changed. Consequently, the amount of proteins, which may affect the metabolism and functional state of the cell, is also changed (Fig. 18).

Fig. 18. Hormonal signals transduction through intracellular receptors.

Complex "hormone - receptor" may be formed directly in the nucleus. Thyroid hormone receptors are always associated with DNA.

Hormones provide a communication (information exchange) between different cells and organs. As a result of these mechanisms, coordination of metabolism and functions of different cells and organs and adequate reaction to changes in the environment are achieved.

The role of extracellular signals not only hormones can performe, but also a number of other substances - cytokines, biogenic amines, neurotransmitters, etc.