Biological Chemistry - Berezov, T. T., Korovkin, B. F. 1998

Hormones
Molecular Mechanisms of Hormonal Signal Transduction

This chapter examined the Chemical Structure of most known Hormones and other biologically active hormone-like substances, as well as the clinical picture associated with their deficiency or overproduction. In several cases, the BIOLOGICAL EFFECTS OF hormones are presented without a detailed Discussion of the mechanisms regulating METABOLISM. Despite the immense diversity of hormones and hormone-like substances, the biological action of most hormones is underpinned by strikingly similar, nearly identical fundamental mechanisms that transmit information from one Cell to another. The following sections will present Examples of the Mechanisms of action of Peptide Hormones (including Amino Acid Derivatives) and Steroid Hormones. Research by E. Sutherland and the Discovery of cyclic adenosine monophosphate (see below) played a monumental role in shaping modern understanding of the subtle molecular mechanisms underlying the biological action of most hormones.

It is well established that the direction and fine-tuning of the signal Transduction process are primarily ensured by the presence of receptor molecules (most commonly Proteins) on The Cell surface that recognize the hormonal signal (see Insulin receptors). The receptors transform this signal into Changes in the concentrations of intracellular messengers, known as secondary messengers, the levels of which are determined by The activity of Enzymes that catalyze their Biosynthesis AND DEGRADATION.

In terms of their chemical nature, the receptors for nearly all BIOLOGICALLY ACTIVE SUBSTANCES are Glycoproteins, with the «recognition» domain (site) of the receptor facing the extracellular space, while the region responsible for coupling the receptor with the effector system (specifically, an enzyme) is located within the thickness of The Plasma Membrane. A common property of all receptors is their high Specificity for a single specific hormone (with an affinity constant ranging from 0.1 to 10 nM). It is also known that the coupling of the receptor to effector systems is mediated by the so-called G-protein, whose function is to ensure the Amplification and repeated transmission of the hormonal signal at the plasma membrane level. In its activated form, the G-protein stimulates the synthesis of cyclic AMP via adenylate cyclase, which triggers a cascade mechanism for activating intracellular proteins.

The common fundamental mechanism through which the biological effects of «secondary» messengers are realized within the cell is the phosphorylation-dephosphorylation of proteins, mediated by A wide variety of protein Kinases. These enzymes catalyze The transfer of the terminal group from ATP to the OH-groups of Serine and Threonine, and in some cases, Tyrosine residues in target proteins. Phosphorylation represents a critical post-translational chemical Modification of protein molecules that profoundly alters both their Structure and function. Specifically, it induces changes in structural properties (such as the association or dissociation of constituent subunits) and activates or inhibits their catalytic properties, ultimately determining The rate of Chemical Reactions and the overall functional activity of Cells.