Reactivities of Amino Acids and Proteins with Iodine
Erwin Regoeczi in Iodine-Labeled Plasma Proteins, 2019
Recent studies indicate that tyrosyl rings are involved in biological processes by stacking (i.e., alignment with other ring structures). Thus, oligopeptides containing tyrosine stack with nucleic acid bases as shown by proton magnetic resonance, fluorescence spectroscopy, and difference absorption spectroscopy.157 This interaction, only demonstrable with single-stranded structures, is not abolished by methylation of the phenoic OH group. Energy transfer from the tyrosine to the nucleic acid is inferred from fluorescence quenching. Tyrosine could therefore possibly play a role in the selective recognition of single strands by proteins. Similarly, tyrosyl residues of flavoproteins stack parallel with flavin, suggesting that the reduction of oxidized flavin may be facilitated by charge transfer.158
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].
Molecular Aspects of the Activity and Inhibition of the FAD-Containing Monoamine Oxidases
Peter Grunwald in Pharmaceutical Biocatalysis, 2019
Comparison of the rat and human MAO structures revealed minor differences reflecting the reported species differences in substrate and inhibitor specificity (Krueger et al., 1995; Hubalek et al., 2005; Ramadan et al., 2007). In all structures, the catalytic FAD is at the end of a tunnel leading from the surface of the protein. The tunnel is generally hydrophobic, ending in an aromatic cage near the flavin where tyrosines (Tyr398 and Tyr435 in MAO B) align the neutral amine substrate towards the C4-N5 region of the flavin. The flavin is bent at about 30° along the N5-N10 axis favouring reduction as shown in Fig. 10.3, and there is a lysine-water-flavin(N5) motif important for the redox reactions of the flavin (Binda et al., 2002).
Purification and characterisation of glutathione reductase from scorpionfish (scorpaena porcus) and investigation of heavy metal ions inhibition
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Glutathione reductase (EC 1.8.1.7; GR), a major enzyme in glutathione metabolism, is required for the maintenance of the reduced form of cellular glutathione, which is strongly nucleophilic for many reactive electrophiles10,11. The flavin enzyme GR acts as an antioxidant to protect cells from oxidative stress by reducing glutathione disulphide (GSSG) to its reduced form (GSH)12. It has an important role in the drug and detoxification mechanisms especially in the liver. This is due to the cytochrome P-450 system found in liver microsomes, which provides detoxifying events13. Maintaining the GSH/GSSG ratio in the cell environment is one of the most important known targets of the GR enzyme-catalysed reactions14. Glutathione reductase is involved in the reduction-oxidation of intracellular glutathione for GSSG, which is generated through the detoxification of hydroperoxides and reduction of some other chemicals catalysed by glutathione perdoxidase15. The NADP+ dependent malate dehydrogenase and pentose phosphate pathways provide the NADPH needed in this catalytic process16,17. NADPH, a key product of the pentose phosphate cycle, is employed extensively in reductive biosynthesis. Furthermore, it aids in the protection of the cell against oxidative damage9.
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).
Related Knowledge Centers
- Adenosine Diphosphate
- Flavin Adenine Dinucleotide
- Flavin Mononucleotide
- Flavoprotein
- Functional Group
- Organic Compound
- Prosthetic Group
- Phosphorylation
- Isoalloxazine
- Riboflavin