Fatty Acid Oxidation
Integrated Metabolism
Lipid-soluble hormones act usually by gene activation/deactivation. Examples of these hormones include steroids, thyroid hormone, and vitamin A (retinoic acid). The hormones are transported through the circulation in association with a hormone-binding protein and are soluble in the plasma membrane of the cell. Their receptors are intracellular, and they act on gene transcription (the synthesis of messenger RNA) rather than at the protein level. Thus, they act more slowly than do the soluble hormones, on the scale of days rather than minutes.
The sequence of events in gene activation contains several steps. First, in the hormone-free state, the unoccupied receptor is bound to the nuclear membrane and loosely to chromatin. (Chromatin is the DNA-protein complex of chromosomes.) After the hormone binds the receptor, it changes its location. The receptor-hormone complex binds DNA tightly and thereby activates or inactivates the synthesis of mRNA from these genes. The specificity of these receptors lies in two properties: their ability to bind different hormones and their ability to bind different DNA sequences.
These receptors share quite similar DNA-binding domains and differ somewhat more in their hormone-binding regions as shown in Figure
1 . Additionally, they have very different
activation domains, which interact with other parts of the transcription machinery.
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Again, the possibility of “cross-talk” exists between metabolic and genetic events. Thus, for example, steroids may bind to one receptor, which itself will interact with other proteins. Some of these proteins may be phosphorylated by kinases that respond to the presence of cAMP or a Ca2+ ion.
