Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: KEGG:D02011 (FAD)
 5,530 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous control studies carried out in children showed that respiratory infection alters riboflavin metabolism and leads to excessive urinary losses of the vitamin. In order to understand the nature of biochemical changes in riboflavin metabolism during respiratory infection, a study was carried out using the mouse as the experimental model, and Klebsiella pneumoniae as the infective organism. Mice were fed on either a low (0.5 mg/kg)- or high (13.3 mg/kg)-riboflavin semi-synthetic diet. Infection resulted in a 5-6-fold higher excretion of riboflavin in the urine of mice fed on the low-riboflavin diet. Higher erythrocyte FAD levels and lower liver FAD levels were also observed during infection. Of the four enzymes involved in the synthesis and breakdown of the flavin coenzymes studied, the activity of hepatic flavokinase (ATP: riboflavin 5'-phosphotransferase; EC 2.7.1.26) was significantly lower, and that of FAD synthetase (ATP: FMN adenylyltransferase; EC 2.7.7.2) was higher during riboflavin restriction and infection. The activity of FMN (acid) phosphatase (EC 3.1.3.2) was unchanged, whereas FAD (nucleotide) pyrophosphatase (EC 3.6.1.9) activity was significantly higher both with the low-riboflavin diet and during infection. Thyroid hormone is known to modulate flavokinase activity and, hence, thyroid status was assessed. Plasma triiodothyronine (T3) levels were not affected, but thyroxine levels were lower in the mice fed on the low-riboflavin diet. However, plasma T3 was significantly lower during infection, suggesting a mechanistic role for the hormone in the reduction of flavokinase activity.
 ...
PMID:Flavin metabolism during respiratory infection in mice. 888 17

Mitochondrial FAD-linked glycerol-3-phosphate dehydrogenase (mtGPDH) is one of the two enzymes of the glycerol phosphate shuttle. This shuttle transfers reducing equivalents from the cytoplasm to the mitochondria in a unidirectional, exothermic manner. Here, the isolation and characterization of the rat nuclear gene (Gpd2) encoding mtGPDH is reported. The mtGPDH gene spans 100 kb and consists of 17 exons. The use of alternate promoters was suggested by the presence of three different first exons and confirmed by transient expression for two of them. The first exons are expressed in a tissue-restricted manner. Exon 1a was found primarily in brain, exon 1b was used in all tissues examined, and exon 1c was detected predominantly in testis. Depending on the tissue, different transcript lengths were also observed: 5.9 kb (all tissues), 3.6 kb (skeletal muscle), and 2.5 kb (testis). The length isoforms are attributable to alternate splicing and polyadenylation site use. Very high mtGPDH mRNA levels were found in brown adipose tissue, 75 fold greater than in white adipose tissue. Thyroid hormone increased mtGPDH mRNA levels in liver and heart but not in brown adipose tissue, brain, or testis. This pattern corresponds to that of thyroid hormone-induced oxygen consumption and is consistent with a role for mtGPDH in thyroid hormone-induced thermogenesis. Both thyroid-responsive and nonresponsive tissues used promoter 1b, suggesting that tissue-specific factor(s) contribute to the tissue-restricted responsiveness to thyroid hormone.
 ...
PMID:Rat mitochondrial glycerol-3-phosphate dehydrogenase gene: multiple promoters, high levels in brown adipose tissue, and tissue-specific regulation by thyroid hormone. 953 10

Several reports have appeared in the literature proving that hypothyroidism is associated with increased risk for cardiovascular disease, especially coronary heart disease. This increased risk for premature atherosclerosis is supported by autopsy and epidemiological studies in patients with thyroid hormone deficiency. Hypothyroid patients have increased diastolic blood pressure (as a result of increased systemic vascular resistance), altered lipid profile (elevated levels of total cholesterol, LDL-cholesterol and apolipoprotein B). More recently homocysteine, C-reactive protein, increased arterial stiffness, endothelial dysfunction and altered coagulation parameters have been recognized as a "new" risk factors for atherosclerosis in patients with thyroid hormone deficiency. The plasma total homocysteine concentration, an independent risk factor for atherosclerosis, is moderately elevated in overtly hypothyroid patients and it decreases with thyroid replacement therapy. Several experimental study have shown that hypothyroidism affects folate metabolism and the enzymes involved in the remetylation pathway of homocysteine (particularly 5,10-methylenotetrahydrofolate reductase - MTHFR). In hypothyroid condition the hepatic activity of flavoenzyme - MTHFR, is decreased. Thyroid hormone may affect the availability of FMN and FAD - necessary for stabilizing MTHFR. An impairment of enzyme involved in transsulfuration pathway is suggested. The increased serum creatinine level in hypothyroidism probably reflects a reduced glomerular filtration rate, which is linked to impaired renal homocysteine clearance and hyperhomocysteinemia.
 ...
PMID:[The influence of thyroid hormones on homocysteine and atherosclerotic vascular disease]. 1633 88