metallothionein and Genetic-Diseases--Inborn

Topics: Animals; Biological Evolution; Cloning, Molecular; Gene Amplification; Gene Expression Regulation; Genetic Diseases, Inborn; Genetic Engineering; Hormones; Humans; Metallothionein; Metals; Methylation; Models, Biological; Protein Conformation; Saccharomyces cerevisiae; Transcription, Genetic

A hypothesis is proposed admitting the participation of apometallothioneines (AMT) as a common link in the etiopathogenesis of hypertonic disease (HD) and some diseases with polygene heredity. The preconditions of the hypothesis are discussed (role of genetic disposition, external factors as salt, stress, tobacco smoking, alcohol, microelements--V and Cd and glucocorticoids in the origination of arterial hypertension). AMT homeostasis is discussed as well as the possible connection with the metabolism of Zn and Cu and Cu in organism. The chelating capacity of AMT makes it a potential regulatory protein, associated with the activity of Zn- and Cu-dependent enzymes and metalloenzymes. The mosaicism of pathology is explained with the genetic polymorphism of those enzymes (D beta H, MAO, etc), regardless of the common etiopathogenetic link. Some schemes are presented illustrating the hypothesis. The tendencies of the future studies are outlined in searching of direct proofs of the hypothesis.

Topics: Adrenal Cortex; Animals; Apoproteins; Blood Pressure; Copper; Disease Models, Animal; Disease Susceptibility; Genes; Genetic Diseases, Inborn; Glucocorticoids; Homeostasis; Humans; Hypertension; Menkes Kinky Hair Syndrome; Metallothionein; Terminology as Topic; Zinc

The requirement of zinc for humans was recognized in the early 1960s. The causes of zinc deficiency include malnutrition, alcoholism, malabsorption, extensive burns, chronic debilitating disorders, and chronic renal diseases; use of certain drugs such as penicillamine and, in some cases, diuretics; and genetic disorders such as acrodermatitis enteropathica and sickle cell disease. The requirement of zinc is increased in pregnancy and during growth. The clinical manifestations of severe zinc deficiency include bullous-pustular dermatitis, alopecia, diarrhea, emotional disorder, weight loss, intercurrent infections, and hypogonadism in males; zinc deficiency can be fatal if unrecognized and untreated. A moderate deficiency of zinc is characterized by growth retardation and delayed puberty in adolescents, hypogonadism in males, rough skin, poor appetite, mental lethargy, delayed wound healing, taste abnormalities, and abnormal dark adaptation. In mild cases of zinc deficiency in human subjects, we have observed oligospermia, slight weight loss, and hyperammonemia. Zinc is a growth factor. As a result of its deficiency, growth is affected adversely in many animal species and humans, probably because zinc is needed for protein and DNA synthesis and cell division. The effects of zinc and growth hormone on growth appear to be independent of each other in experimental animals. Whether zinc is required for the metabolism of somatomedin needs further investigation. Thyroid and adrenal functions do not appear to change as a result of zinc deficiency. Glucocorticoids may have an effect on zinc metabolism, although the clinical relevance of this effect is not known at present. In contrast, testicular function is affected adversely as a result of zinc deficiency in both humans and experimental animals. The effect appears to be a direct one since the hypothalamic-pituitary axis is intact, and may relate to the reduction in testicular size as a result of the need for zinc in cell division. In addition, zinc is required for the function of several testicular enzymes, although a specific role in steroidogenesis has not been identified. Zinc appears to have a role in the modulation of prolactin secretion, in the secretion and action of insulin, and in the production and biologic effects of thymic hormones. It is clear that the endocrine consequences of zinc deficiency are multiple, and that continued investigation should provide additional pathophysiologic and therapeutic i

Topics: Burns; Cell Membrane; Chronic Disease; Endocrine Glands; Enzymes; Female; Gastrointestinal Diseases; Genetic Diseases, Inborn; Growth; Humans; Immunity; Kidney Diseases; Metallothionein; Nucleic Acids; Pregnancy; Skin Diseases; Zinc