The Iodotyrosine Deiodinase Defect
Geraldo Medeiros-Neto, John Bruton Stanbury in Inherited Disorders of the Thyroid System, 2019
Activity is stimulated by sodium dithionate in the absence of NADPH,118 and the rate of deiodination is dependent on the quantity of NADPH.114 The dithionate might reduce the flavins. Kusakabe and Miyaki observed that the fraction from a supernatant of homogenate of thyroid migrated toward the anode on electrophoresis, while that solubi-lized from the particulate fraction migrated toward the cathode.115 This suggested that the iodotyrosine deiodinase existed in two isoforms. The removal of the first iodine from diidotyrosine occurs less rapidly than does the deiodination of monoiodotyrosine. Substances such as menadione, methelene blue, and phenazine methosulfate inhibit deiodination even when supplemented with NADPH, probably by accelerating NADPH oxidation.116 Serotonin, acetylcholine, epinephrin, and ferricyanide also inhibit deiodination. Prior injection of nicotinamide into rats stimulates the capacity of liver homogenates to deiodinate DIT, probably by stimulating the concentration of NADPH in the tissue.124 MIT and DIT block tyrosine hydroxylase, but it is not clear what function this might serve, if any.119 It also inhibits dopamine synthesis and induces hyperprolactinemia and hyperaldosteronemia.125-127
Application of Nonlinear Microscopy in Life Sciences
Lingyan Shi, Robert R. Alfano in Deep Imaging in Tissue and Biomedical Materials, 2017
Flavins, fluorescent molecules derived from riboflavin, are important sources of autofluorescence in the green spectral range. Biologically most important are flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN). These are cofactors of many enzymatic reactions, often connected to cellular metabolism (FMN takes part in the electron transport chain, FAD is involved in citric acid cycle and in oxidative phosphorylation). FAD, together with NADH, was used as a basis for calculating redox ratio [123] to enhance the sensitivity with which precancerous cells can be discriminated. The fluorescence lifetime of FAD is also strongly dependent on its binding state, but unlike that of NADH, the lifetime of bound FAD is much shorter than that of the free molecule [19].
Natural Supplements in Pain Management: A Primer and Evidence-Based Review
Mark V. Boswell, B. Eliot Cole in Weiner's Pain Management, 2005
Riboflavin is an important vitamin in its actions as a precursor of flavin adenine dinucleotide and flavin mononucleotide. Dysfunction of these coenzymes has been linked to electron transport chain abnormalities and poor cerebrovascular tone, both of which have a potential role in migraine pathogenesis (Welch & Ramadan, 1995). An intention-to-treat analysis of 55 patients using 400 mg/day over 3 months demonstrated decreased headache days by 59% versus 15% for placebo. In this study the NNT to reach significance was 2.3. As with other supplements, an extended use of supplement for several months was necessary before clinical improvement was noted. Side effects are rare and typically GI in nature.
A case report of sudden-onset auditory neuropathy spectrum disorder associated with Brown-Vialetto-Van Laere syndrome (riboflavin transporter deficiency)
Published in International Journal of Audiology, 2022
Ozlem Gedik Soyuyuce, Elif Ayanoglu Aksoy, Zuhal Yapici
The flavin deficiencies associated with BVVL may cause dysfunction in auditory neuron firing and thus auditory dyssynchrony (Chandran et al. 2015). The time between the onset of deafness and the development of other manifestations varies but is usually one to two years. An intercurrent event (usually an injury or infection) appears to precipitate the initial manifestations or worsen existing findings (Summers et al. 1987). Since no intercurrent event was reported by the parents of our case, it remains unclear what caused the fluctuations and worsening in auditory findings, as well as the progression of disease with additional severe neurological symptoms within months. However, the fluctuations with the ABR wave presentation due to a probable gradual loss of function of riboflavin transporter proteins early in disease course might be associated with the dyssynchrony at the periphery of the auditory system similar to fluctuations observed in temperature-sensitive ANSD (Moser and Starr 2016). Fluctuations with the ABR wave presentation might indicate that the nerves were still recoverable during the earliest stage. However, after a long duration of illness, total nerve dyssynchrony sets in, and a total absence of waveforms suggests complete damage (Chandran et al. 2015).
Exploring the contribution of mitochondrial dynamics to multiple acyl-CoA dehydrogenase deficiency-related phenotype
Published in Archives of Physiology and Biochemistry, 2021
Sofia R. Brandão, Rita Ferreira, Hugo Rocha
Riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (RR-MADD) is a variant of MAD defects, which benefit from riboflavin treatment, with a clinical improvement and an almost normalization of biochemical abnormalities (Gregersen et al.1982). Riboflavin is the precursor of FAD, which is a cofactor for many enzymes such as acyl-CoA dehydrogenases, ETFDH and other mitochondrial enzymes, being also essential for the folding and stability of these flavoproteins (Olsen et al.2003, Ho et al.2011). Patients with RR-MADD showed milder folding defects of ETFDH variants, with a significant increase in protein stability and activity after riboflavin treatment (Cornelius et al.2013). In addition of ETFDH mutations, other RR-MADD phenotype-like may be caused by defects in flavin metabolism and transport (Olsen et al.2007, 2016). Most of the patients with late-onset MADD are clearly responsive to riboflavin, since they usually present a missense mutation on the ETFDH gene which is more commonly associated with RR-MADD phenotypes (Grünert 2014). However, severe MADD forms may also be associated to ETFDH mutations (Rocha et al.2011, Alves et al.2012).
Differential effects of C-reactive protein levels on voriconazole metabolism at three age groups in allogeneic hematopoietic cell transplant recipients
Published in Journal of Chemotherapy, 2021
Xingxian Luo, Taifeng Li, Lei Hu, Silu Liu, Haiyan Zhao, Jiaqi Zhang, Yufei Feng, Lin Huang
In the present study, the median concentration of VRCZ was highest in adults (1.48 mg/L), followed by children aged 10–18 (0.85 mg/L), and the lowest was children aged 2–10 years (0.65 mg/L), which were partly consistent with wei et al reported.10 Conversely, the order of the magnitude of the MR values was aged in 2–10 years (1.72), then in 11–18 years (1.21) and followed in 19–60 years (0.95), further verifying that metabolic rate of VRCZ exhibits negative relationship with age groups. Mann–Whitney U test suggested that MR values in 11–18 and 19–60 years were significantly lower in age 2–10 years (p < .05), indicating a higher activity of CYP2C19 enzyme in age 2–10 years. Existing evidence support that higher metabolic activity of flavin-containing monooxygenase 3 (FMO3) and CYP2C19 are found in children compared with adults.23 A higher metabolic intensity of VRCZ in younger children would reduce the impact of inflammation on liver microsomal enzyme activity. With the increase of age, the impact of inflammation on VRCZ metabolism seemed to be more and more prominent.
Related Knowledge Centers
- Adenosine Diphosphate
- Flavin Adenine Dinucleotide
- Flavin Mononucleotide
- Flavoprotein
- Functional Group
- Organic Compound
- Prosthetic Group
- Phosphorylation
- Isoalloxazine
- Riboflavin