Mechanisms of hormone action.

Circulating hormones play an important role in regulating the flux through metabolic pathways. In general, hormones regulate either the activity of key enzymes of metabolism or the activity of protein transport systems such as those found in the plasma membrane and in the inner mitochondrial membrane. Little is known about the mechanism of action of hormones on transport systems, so the discussion in this article will be confined to the mechanism of action of hormones on key enzymes of metabolism. Hormones regulate the activity of key enzymes of metabolism in two ways. Many hormones whose effects on metabolism develop relatively rapidly (for example glucagon or adrenaline) regulate the activities of enzymes via covalent modifications such as the phosphorylation or dephosphorylation of specific serine residues of the enzyme protein. Such alterations in the phosphorylation state of the enzyme are brought about by changes in the activities of either protein kinases which catalyse phosphorylation reactions or phosphoprotein phosphatases which catalyse dephosphorylation reactions. Phosphorylation or dephosphorylation change the kinetic properties of enzymes in one of two ways: either the maximal catalytic activity of the enzyme changes or the affinity of the enzyme for its substrates, activators or inhibitors changes. As a result, the flux through the enzyme-catalysed reaction changes in response to the hormone. It is likely that other covalent modifications such as the adenylation and deadenylation of specific tyrosine residues also occur in mammalian cells, but so far this covalent modification has been studied only with bacterial enzymes.