flavin-adenine-dinucleotide and Hypothyroidism

Topics: Adenine Nucleotides; Adenosine Triphosphate; Animals; Dactinomycin; Flavin Mononucleotide; Flavin-Adenine Dinucleotide; Hyperthyroidism; Hypothyroidism; In Vitro Techniques; Iodine Isotopes; Liver; Male; Phosphotransferases; Rats; Riboflavin; Thyroid Hormones; Thyroxine

A full-length 2.4-kb cDNA for the FAD-linked glycerol-3-phosphate dehydrogenase (EC 1.1.99.5) was cloned from rat liver using PCR techniques. The cloned gene encodes a protein of 727 amino acids. The calculated molecular mass of 80,898 Da is higher than the apparent molecular mass observed by SDS/PAGE (74,000 Da) of the purified enzyme. This result indicates that the enzyme is synthesized as a precursor with a putative mitochondrial signal sequence. mRNA for this gene was detected in liver, heart, muscle, brain, testes, and pancreas. With the exception of testes, basal expression levels were very low in all tissues examined. However, application of thyroid hormones led to a 10- to 15-fold increase in liver glycerol-3-phosphate dehydrogenase mRNA, whereas hypothyroidism further decreased the mRNA level.

Topics: Amino Acid Sequence; Animals; Bacillus subtilis; Base Sequence; Brain; Cloning, Molecular; DNA, Complementary; Flavin-Adenine Dinucleotide; Gene Expression Regulation, Enzymologic; Glycerolphosphate Dehydrogenase; Hyperthyroidism; Hypothyroidism; Liver; Male; Mitochondria, Liver; Molecular Sequence Data; Molecular Weight; Muscles; Myocardium; Organ Specificity; Pancreas; Polymerase Chain Reaction; Rats; Rats, Wistar; Recombinant Proteins; RNA, Messenger; Saccharomyces cerevisiae; Sequence Homology, Amino Acid; Testis; Thyroid Hormones

In the hypothyroid rat the flavin adenine dinucleotide (FAD) content of the liver is similar to that observed in rats maintained on a riboflavin-deficient diet. Thyroxine regulates the enzyme flavin kinase. Human adults with hypothyroidism have levels of erythrocyte glutathione reductase (EGR), an FAD-containing enzyme, in the range indicative of riboflavin deficiency, which can be corrected with thyroxine therapy. In the present study six newborns with severe congenital hypothyroidism because of athyrosis, ectopic thyroidism, or congenital hypothyroidism with Down's syndrome had normal levels of EGR, and treatment with thyroxine had no effect on these levels.

Topics: Congenital Hypothyroidism; Erythrocytes; Flavin-Adenine Dinucleotide; Glutathione Reductase; Humans; Hypothyroidism; Infant, Newborn; Riboflavin; Thyroxine

The means by which thyroid hormone regulates flavocoenzyme biosynthesis was studied in hyper-, eu-, and hypothyroid rats by determining the activities of flavocoenzyme-forming enzymes, viz., flavokinase and FAD synthetase, as well as those of flavocoenzyme-degrading enzymes, viz., FMN phosphatase and FAD pyrophosphatase. Flavokinase activity was increased in hyperthyroid animal and decreased in hypothyroid animals. Correspondence of flavokinase activity with the amount of a high-affinity flavin-binding protein quantitated immunologically in hypo-, eu-, and hyperthyroid rats indicated that the thyroid response is caused by an increased amount of enzyme; moreover, the concomitant decrease in a low-affinity flavin-binding protein suggests an inactive precursor form of flavokinase. FAD synthetase activity showed a similar but less pronounced trend than flavokinase. Activities of FMN phosphatase and FAD pyrophosphatase were not influenced by thyroid hormone. Overall results indicate that the mechanism of thyroid hormone regulation of flavocoenzyme level is in the steps of biosynthesis, especially at flavokinase, rather than in degradation steps.

Topics: Animals; Flavin Mononucleotide; Flavin-Adenine Dinucleotide; Hyperthyroidism; Hypothyroidism; Liver; Male; Nucleotidases; Nucleotidyltransferases; Phosphotransferases; Phosphotransferases (Alcohol Group Acceptor); Pyrophosphatases; Rats; Rats, Inbred Strains; Thyroid Hormones

Topics: Animals; Erythrocytes; Flavin-Adenine Dinucleotide; Glutathione Reductase; Hyperthyroidism; Hypothyroidism; In Vitro Techniques; Liver; Male; Rats; Thyroxine

Topics: Animals; Enzyme Induction; Flavin-Adenine Dinucleotide; Glyceraldehyde-3-Phosphate Dehydrogenases; Hypothyroidism; Iodine Isotopes; Mitochondria, Liver; Rats; Riboflavin; Riboflavin Deficiency; Starvation; Stimulation, Chemical; Triiodothyronine

Topics: Animals; Flavin Mononucleotide; Flavin-Adenine Dinucleotide; Hypothyroidism; Liver; Male; Rats; Riboflavin Deficiency

Topics: Animals; Flavin Mononucleotide; Flavin-Adenine Dinucleotide; Hyperthyroidism; Hypothyroidism; Liver; Male; Nucleotidyltransferases; Phosphoric Monoester Hydrolases; Phosphotransferases; Rats; Thyroidectomy; Thyroxine

Topics: Animals; Flavin-Adenine Dinucleotide; Glycerolphosphate Dehydrogenase; Hypothyroidism; Iodine Radioisotopes; Male; Mitochondria, Liver; Rats; Riboflavin Deficiency; Triiodothyronine

Topics: Alcohol Oxidoreductases; Animals; Body Weight; Flavin Mononucleotide; Flavin-Adenine Dinucleotide; Glycolates; Hypothyroidism; Liver; Male; Microsomes; NADP; Organ Size; Oxidoreductases; Phosphotransferases; Rats; Riboflavin Deficiency