Riboflavin alcohol

Riboflavin forms fine yellow to orange-yeUow needles with a bitter taste from 2 N acetic acid, alcohol, water, or pyridine. It melts with decomposition at 278—279°C (darkens at ca 240°C). The solubihty of riboflavin in water is 10—13 mg/100 mL at 25—27.5°C, and in absolute ethanol 4.5 mg/100 mL at 27.5°C it is slightly soluble in amyl alcohol, cyclohexanol, benzyl alcohol, amyl acetate, and phenol, but insoluble in ether, chloroform, acetone, and benzene. It is very soluble in dilute alkah, but these solutions are unstable. Various polymorphic crystalline forms of riboflavin exhibit variations in physical properties. In aqueous nicotinamide solution at pH 5, solubihty increases from 0.1 to 2.5% as the nicotinamide concentration increases from 5 to 50% (9). 

A hypothesis for the oxidation of purines in the presence of this enzyme has been elaborated by Bergmann and his colleagues. It postulates that the purine, often in one of its less prevalent tautomeric forms, is adsorbed on the protein, or the riboflavin coenzyme, of the enzyme then hydration occurs under the influence of the electronic field of the enz5rme, and this must involve a group that is not sterically blocked by the enzyme but which is accessible to the electron-transport pathway of the riboflavin moiety. Finally, the secondary alcohol is assumed to be dehydrogenated in this pathway to give a doubly... 

Where patients are at risk of Wernicke s encephalopathy - for example, because of chronic alcohol abuse, hyperemesis gravidarum, or malnutrition - they should be given thiamine. In many countries no intravenous preparation of thiamine alone is available, and the compound preparations that are available are prone to cause anaphylactoid reactions, so they should be given by slow infusion, and with adequate facilities for resuscitation. A high potency preparation (Pabrinex ) that contains thiamine 250 mg in 10 ml with ascorbic acid, nicotinamide, pyridoxine and riboflavin, can be given by intravenous infusion over 10 min. 

Riboflavin (vitamin B2 6.18) consists of an isoalloxazine ring linked to an alcohol derived from ribose. The ribose side chain of riboflavin can be modified by the formation of a phosphoester (forming flavin mononucleotide, FMN, 6.19). FMN can be joined to adenine monophosphate to form flavin adenine dinucleotide (FAD, 6.20). FMN and FAD act as co-enzymes by accepting or donating two hydrogen atoms and thus are involved in redox reactions. Flavoprotein enzymes are involved in many metabolic pathways. Riboflavin is a yellow-green fluorescent compound and, in addition to its role as a vitamin, it is responsible for the colour of milk serum (Chapter 11). 

The dehydrogenation of an alcohol to a ketone or aldehyde (Eq. 15-1) is one of the most frequent biological oxidation reactions. Although the hydrogen atoms removed from the substrate are often indicated simply as 2[H], it was recognized early in the twentieth century that they are actually transferred to hydrogen-carrying coenzymes such as NAD+, NADP+, FAD, and riboflavin... 

Several of the B vitamins function as coenzymes or as precursors of coenzymes some of these have been mentioned previously. Nicotinamide adenine dinucleotide (NAD) which, in conjunction with the enzyme alcohol dehydrogenase, oxidizes ethanol to ethanal (Section 15-6C), also is the oxidant in the citric acid cycle (Section 20-10B). The precursor to NAD is the B vitamin, niacin or nicotinic acid (Section 23-2). Riboflavin (vitamin B2) is a precursor of flavin adenine nucleotide FAD, a coenzyme in redox processes rather like NAD (Section 15-6C). Another example of a coenzyme is pyri-doxal (vitamin B6), mentioned in connection with the deamination and decarboxylation of amino acids (Section 25-5C). Yet another is coenzyme A (CoASH), which is essential for metabolism and biosynthesis (Sections 18-8F, 20-10B, and 30-5A). 

Since reduced flavins, pteridine derivatives, and PQQ can be readily oxidized by oxygen to regenerate the oxidized forms [59-62], these coenzyme analogs can act as photocatalysts when the oxidation of substrates by the coenzymes occurs photochemically. No appreciable photooxidation of benzyl alcohol by oxygen occurs when aminopterin (AP), lumazine (Lu), or riboflavin-tetraacetate (FI) is used as a photocatalyst in the absence of acid in MeCN. When HC104 is added to this system, however, the flavin and pteridine derivatives are protonated as described above, and each proton-ated species (catH+) can act as an efficient photocatalyst for the oxidation of benzyl alcohol derivatives (X-C6H4CH2OH) by oxygen [70] ... 

All of the B2 vitamers are unstable at alkaline pH the coenzymes are also degraded below pH 5.0 (80 - 82). As a result, analysis of the endogenous coenzymes needs to be carried out at pH 5.0-7.0, while total riboflavin (as riboflavin) is best determined at acidic pH. Riboflavin is soluble in water and short-chain alcohols, but insoluble in ether, chloroform, and acetone. The coenzymes are water soluble. 

Solid-phase extraction is routinely used to clean up extracts prior to quantitation (19,42,70, 80-82). Alternatively, endogenous fluorescent artifacts in food samples can be eliminated by oxidation with potassium permanganate/hydrogen peroxide/sodium metabisulphite. Benzyl alcohol has been used to extract riboflavin selectively without the coenzymes, permitting the determination of free riboflavin. 

Alcohol is distilled up to a content of 96% in one or more stages. About 1 % of ethanol consists of fusel oils (degradation products of amino acids) which can be used as solvents for lacquers and resins. Solids from the processed liquor containing proteins, carbohydrates, mineral salts, riboflavin and other vitamins are used in poultry, swine and cattle feeds. C02 and H2 produced in butanol-acetone-butyric acid production can be used for the chemical synthesis of methanol and ammonia, or are burned. 

Riboflavin is produced by Clostridium, Ascomycetes and Candida species. The yield can be as high as 5 g 1 1 after 7 days 60). Gibberella fujikuroi is utilized for the synthesis of gibberellins, a group of plant hormones used for plant growth promotion. Glucose, molasses, lipid (corn oil) are usually used as carbon sources. Vitamin B12 may also be synthesized from alcohols and hydrocarbons. 

Riboflavin occurs as a yellow to orange-yellow, crystalline powder. When dry, it is not affected by diffused light, but when in solution, light induces deterioration. It melts at about 280° with decomposition, and its saturated solution is neutral to litmus. One gram dissolves in 3000 to about 20,000 mL of water, the variations being due to differences in the internal crystalline structure. It is less soluble in alcohol than in water. It is insoluble in ether and in chloroform, but it is very soluble in dilute solutions of alkalies. 

Both drugs and compounds naturally present in foods may compete with vitamins for absorption. Chlorpromazine, tricyclic antidepressants, and some antimalarial dmgs inhibit the intestinal transport and metabolism of riboflavin (Section 7.4.4) carotenoids lacking vitamin A activity compete with /S-carotene for intestinal absorption and metabolism (Section 2.2.2.2) and alcohol inhibits the active transport of thiamin across the intestinal mucosa (Section 6.2). 

As shown in Figure 7.1, riboflavin consists of a tricyclic dimethyl-isoalloxazine ring conjugated to the sugar alcohol ribitol. The metabolically active coenzymes are riboflavin 5 -phosphate and flavin adenine dinucleotide (FAD). In some enzymes the prosthetic group is riboflavin, bound covalently at the catalytic site. 

Although the ribitol moiety is not involved in the redox function of the flavin coenzymes, both the stereochemistry and nature of the sugar alcohol are important. Although some riboflavin analogs have partial vitamin action. 

More convenienfly, compound (13) was directly condensed with barbituric acid (14) in acetic acid (28) or in the presence of an acid catalyst in an organic solvent (29). The same a2o dye intermediate (13) and alloxantin give riboflavin in the presence of palladium on charcoal in alcoholic hydrochloric acid under nitrogen. This reaction may involve the reduction of the a2o group to the <)-phenylenediamine by the alloxantin, which is dehydrogenated to alloxan (see Urea) (30). 

Riboflavin deficiency is often seen in chronic alcoholics due to their poor dietetic habits. 

A minority of alcoholics develop nutrient deficiencies. In Western countries, alcoholics represcrit the largest population segment that can benefit from dietary intervention. Alcoholics are at risk for deficiencies in folate, thiamin, riboflavin, vitamin B, vitamin A, and magnesium, particularly when the intake of these substances is low. In some cases, absorption of the nutrient is impaired in others, catabolism of the nutrient is iitcreased. Thiamin deficiency is a firmly established consequence of alcoholism, as discussed in the iTiiamin section. 

---