Riboflavin related flavins

Riboflavin (2) and some related flavins are pigments of potential importance for aquatic photochemistry that exist at low concentrations in natural waters. These compounds have broad, moderately strong absorption bands in the visible region at about 440 nm and show high quantum yields for triplet formation (Heelis, 1982). 

In the s3mthesis of riboflavin and some related flavins, better yields are often available through the use of 5-chloro- or 5,5-dichlorobarbituric acid place of alloxan. In addition to riboflavin, 6-methyl-9-2 i, y-methyl-g- s, 6-ethyl-9-3 , 7-ethyl-9-2 , 6,7-diethyl-9- , 6-ethyl-7-methyl-9-2 .3 , 5,7-di-niethyl-9- , 6,8-dimethyl-9- , 6,7-dichloro-9-29.72 6-chloro-9-3 -, 6-flu-oro-9-3 , 6,7-dibromo-9- , 5,6-dimethyl-9- , 6-chloro-7-methyl-9-2 , 6-meth-yl-7-chloro-9-, 3,6,7-trimethyl-9-(i -D-ribityl)isoalloxazine2 (using 2-methylalloxan), and 6,7-dichloro-9-(i -D-sorbityl)isoalloxazine i have been prepared by this method. 

Both flavin adenine dinucleotide and the closely related flavin mononucleotide (FMN) contain riboflavin (page 163) as an essential component. Riboflavin, a member of the vitamin B complex, is a derivative of isoalloxazine to which is attached ribitol, a pentahydroxy alcohol related to ribose. FMN consists of riboflavin esterified with phosphate on C-5 of the ribitol. 

A closely related flavin has been found in cultures of Streptomyces davawensis by Japanese researchers. The structure of this compound, which was called roseoflavin because of its deep red colour (abs. max. 496 nm), was ascertained by oxidative degradation of the ribityl side chain and subsequent X-ray crystallography of the 2 -acetyl derivative (130). It represents the 8-nor-8-dimethylamino derivative of riboflavin (19) and is thus an analog of 8a-aminoflavin types synthetized earlier by Hemmerich et al at the lumiflavin (75) and Berezowskii at the riboflavin level (5). 

Hickey " observed an interesting reduction of riboflavin by Streptococcus faecalis to green and reddish orange products, which may be related to the well-known verdo- and rhodo-flavin. 

Milk is a good source of riboflavin whole milk contains about 0.17 mg per 100 g. Most (65-95%) of the riboflavin in milk is present in the free form the remainder is present as FMN or FAD. Milk also contains small amounts (about 11% of total flavins) of a related compound, 10-(2 -hydroxyethyl) flavin, which acts as an antivitamin. The concentration of this compound must be considered when evaluating the riboflavin activity in milk. The concentration of riboflavin in milk is influenced by the breed of... 

When taken up by the body, riboflavin is converted into its coenzyme forms (Chapter 25) and any excess is quickly excreted in the urine. Urine also contains smaller amounts of metabolites. The ribityl group may be cut by the action of intestinal bacteria acting on riboflavin before it is absorbed. The resulting 10-hydroxyethyl flavin may sometimes be a major urinary product.c d The related 10-formylmethyl flavin is also excreted,0 as are small amounts of 7a- and 8a- hydroxyriboflavins, apparently formed in the body by hydroxylation. These may be degraded farther to the 7a- and 8a- carboxylic acids of lumichrome (riboflavin from which the ribityl side chain is totally missing).6 A riboflavin glucoside has also been found in rat urine.f... 

The reactive part of FAD is its isoalloxazine ring, a derivative of the vitamin riboflavin (Figure 14.15). FAD, like NAD can accept two electrons. In doing so, FAD, unlike NAD+, takes up two protons. These carriers of high-potential electrons as well as flavin mononucleotide (FMN), an electron carrier related to FAD, will be considered further in Chapter 18. 

Nicotiana tabacum L. in relation to riboflavin, ribofla-vin-5-phosphate, and flavin adenine dinucleotide content Plant Physiol. 35 (1960) 516-520. 4972. 

Riboflavin is important in human nutrition. Riboflavin is converted to the active flavin nucleotides flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN). Riboflavin deficiency has been related to foetal malformations and anaemia. 

Synthesis of riboflavin and related biologically active flavins... 

Acyl CoA Dehydrogenases. Reaction (2) is catalyzed by a family of related enzymes. The lower fatty acid derivatives are oxidized by an enzyme purified from beef liver mitochondria. The isolated enzyme, butyryl dehydrogenase, has been reported to contain both riboflavin and copper.The nature of this enzyme will be discussed later in conjunction with other flavin enzjnmes. Chains of 3 to 8 carbons are oxidized in the presence of suitable electron acceptors, including 2,6-dichloro-phenolindophenol, cytochrome c, and ferricyanide. The maximum rate is obtained with butyryl CoA. It has been reported that the initial oxidation of fatty acid-CoA and the reduction of the employed electron acceptors are carried out by two different flavoproteins, which react with each... 

The increased flavin production by E. ashbyii in the presence of threonine has led Goodwin and Pendlington (6 ) to propose formation of the o-xylene portion of riboflavin by condensation of the carbon skeletons of two threonine molecules. It has been pointed out that such a mechanism is inconastent with the label pattern of ring A obtained with acetate-l-C with A. goaaypii, in relation to known pathways of threonine formation (64). As an alternative, one could postulate threonine being cleaved to acetaldehyde and glycine by threonine aldolase 84, 86). 

Hans and co-workers also examined the enzyme from the related organism Clostridium symbiosum. Here, the heterodimer component D (a, 54 kDa P, 42 kDa) contains two [4Fe-4S] clusters, one molecule of FMN and varying amounts (<0.2) of riboflavin. Mdssbauer spectroscopy revealed the symmetric cube-type structures of the two [4Fe-4S] clusters, while EPR showed that the clusters were resistant to reduction. A narrow signal atg = 2.004 was assigned to a rather stable flavin radical. The authors concluded that the substoichiometric amount of riboflavin found to date in all 2-hydroxyacyl-CoA dehydratases appears to be unnecessary for activity but nevertheless represents a characteristic feature of this class of enzymes. 

Use of physiological functional indices in relation to riboflavin deficiency (analogous to dark adaptation for vitamin A clotting factors for vitamin K, etc.) has not proved possible, because the analogous riboflavin-sensitive physiological processes are insufficiently specific or easily measurable for use in population studies. Of the biochemical indices, urinary excretion and the flavin-dependent enzyme, erythrocyte glutathione reductase, are generally considered to be the front-runners in the race for acceptance in human studies. These have already been described in the previous section. 

Although neither free nor phosphorylated riboflavin has an absorption spectrum similar to that of visual purple, Morton further recalls that intense red intermediate products are formed when riboflavin, or related compounds such as lumiflavin, are reduced in strongly acid solution (25,26). A red compound, presumably a flavin-pyridine-nucleotide, is moreover... 

In the last few years a further type of modified flavocoenzyme has beeen discovered which is structurally related to the coenzymes of succinate dehydrogenase and monoamine oxidase, but differs considerably in its chemical properties. Early literature reports indicated the presence of a flavin in cytochrome C552 from Chromatium which could not be extracted with trichloroacetic acid or acidic ammonium sulfate (7), but could be released, for example by trypsin digestion or by incubation with saturated urea solutions (2). Absorption, fluorescence and ESR behaviour were closely similar to those of 8a-cysteinyl-ribo-flavin (12) and indicated the presence of a covalent link to the protein, through position 8a (185). Strong acid hydrolysis of these peptides liberated the flavin as mixture of riboflavin derivatives oxidation with per-formic acid and acid dephosphorylation yielded a homogeneous riboflavin derivative, which was identical with 8-nor-8-carboxy-riboflavin (185). 

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