Riboflavin vitamin excretion

Fourteen cases of acute boric acid ingestion were reported in New York City over 30 months. In these patients excretion of urinary riboflavin (vitamin B2) was determined, and in about two-thirds it was significantly increased. This is not surprising, since riboflavin and boric acid are known to form a water-soluble complex. The range of lethal doses is 1-3 g for babies, 5 g for infants, and 15-20 g for adults. 

Carlucci and Bowes [29] showed that vitamin production in phytoplankton algae was attributed to release during exponential growth and upon cell death and lysis in old cultures. Vitamin utilization was readily observed in cultures of two species S. costatum produced utilizable biotin for Amphidinium carterae. The amount of utilizable vitamin and the rate at which it was exuded depended on the algal species and conditions of culturing. Aaronson et al. [149] showed that when O. danicus (chrysophyceae) was grown on a defined medium the cells excreted a number of vitamins including riboflavin, vitamin E and nicotinic acid in addition to four amino acids. Swift [150] published an excellent review of phytoplankton production, excretion and utihzation of vitamins. 

In foods vitamin B2 occurs free or combined both as FAD and FMN and complexed with proteins. Riboflavin is widely distributed in foodstnffs, but there are very few rich sources. Only yeast and liver contain more than 2mg/100g. Other good sources are milk, the white of eggs, fish roe, kidney, and leafy vegetables. Since riboflavin is continuously excreted in the urine, deficiency is qnite common when dietary intake is insufficient. The symptoms of deficiency are cracked and red lips, inflammation of the lining of the month and tongue, mouth ulcers, cracks at the comer of the mouth, and sore throat. Overdose of oral intake present low toxicity, probably explained by the limited capacity of the intestinal absorption mechanism [417]. 

Vitamins are chemically unrelated organic compounds that cannot be synthesized by humans and, therefore, must must be supplied by the diet. Nine vitamins (folic acid, cobalamin, ascorbic acid, pyridoxine, thiamine, niacin, riboflavin, biotin, and pantothenic acid) are classified as water-soluble, whereas four vitamins (vitamins A, D, K, and E) are termed fat-soluble (Figure 28.1). Vitamins are required to perform specific cellular functions, for example, many of the water-soluble vitamins are precursors of coenzymes for the enzymes of intermediary metabolism. In contrast to the water-soluble vitamins, only one fat soluble vitamin (vitamin K) has a coenzyme function. These vitamins are released, absorbed, and transported with the fat of the diet. They are not readily excreted in the urine, and significant quantities are stored in Die liver and adipose tissue. In fact, consumption of vitamins A and D in exoess of the recommended dietary allowances can lead to accumulation of toxic quantities of these compounds. 

Today, biochemical deficiency of riboflavin is accepted in the absence of clinical signs of deficiency. Biochemical signs of deficiency include change in the amount of the vitamin which is excreted in the urine, or change in the level of activity of a red blood cell (erythrocyte) enzyme, which is known as the erythrocyte glutathione reductase. Requirements for the vitamin are defined as that amount which will prevent both clinical and biochemical signs of deficiency. 

Tucker et al. showed that both sudden severe physical exercise and longer sustained work on a treadmill during training decreases urinary riboflavin excretion during the experimental periods (12) The acute reduction in riboflavin excretion observed by these investigators was attributed to a reduction in renal plasma flow. In order to explain the long-term reduced excretion of the vitamin, they proposed that riboflavin was retained for incorporation into "new muscle tissue". The significance of this study is that if the hypotheses... 

There is no evidence of any significant storage of riboflavin in addition to the limited absorption, any surplus intake is excreted rapidly thus, once metabolic requirements have been met, urinary excretion of riboflavin and its metabolites reflects intake until intestinal absorption is saturated. In depleted animals, the maximum growth response is achieved with intakes that give about 75% saturation of tissues, and the intake to achieve tissue saturation is that at which there is quantitative urinary excretion of the vitamin. 

Control over tissue concentrations of riboflavin coenzymes seems to be largely by control of the activity of flavokinase, and the synthesis and catabolism of flavin-dependent enzymes. Almost all the vitamin in tissues is enzyme bound, and free riboflavin phosphate and FAD are rapidly hydrolyzed to riboflavin. If this is not rephosphorylated, it rapidly diffuses out of tissues and is excreted. 

Under normal conditions, about 25% of the urinary excretion of riboflavin is as the unchanged vitamin, with a small amount as a variety of glycosides of riboflavin and its metabolites. Riboflavin-8-a-histidine andriboflavin-8-a-cysteine arising from the catabofism of enzymes in which the coenzyme is covalently bound are excreted unchanged. 

A number of fungi have a failure of the normal regulation of riboflavin synthesis and are overproducers of the vitamin. Mutants of Ashbya gossypii may accumulate up to 150 /xmol of riboflavin per gram of protein, compared with a normal content of 0.25 /xmol per gram of protein. They can produce and excrete so much that riboflavin crystallizes in the culture medium. Such fungi are used for the commercial production of riboflavin by fermentation, as an alternative to chemical synthesis. 

Two methods of assessing riboflavin status are generally used urinary excretion of the vitamin and its metabolites, and activation of EGR. Criteria of riboflavin adequacy are shown in Table 7.5. 

Clinical signs of riboflavin deficiency are seen at intakes below about 1 mg per day. At intakes below about 1.1 mg per day, there is very little urinary excretion of riboflavin thereafter, as intake increases, there is a sharp increase in excretion. Up to about 2.5 mg per day, there is a linear relationship between intake and excretion. At higher levels of intake, excretion increases sharply, reflecting active renal secretion of excessive vitamin (Section 7.2.5). 

Indices of Vitamin E Nutritional Status Reference Intakes of Vitamin K Indices of Thiamin Nutritional Status Reference Intakes of Thiamin Tissue Flavins in the Rat Urinary Excretion of Riboflavin Metabolites... 

The vitamin is commercially available as riboflavin, riboflavin S-phosphate. and riboflavin S-phosphate sodium. The phosphate esters are used commercially only in multivitamin preparations, and they are hydrolyzed before absorption occurs. Ab.sorption occurs through an active transport. system in which riboflavin is phosphorylated by the intestinal mucosa during absorption. Food and bile enhance absorption. Riboflavin is distributed widely in the body, with limited stores in the liver, spleen, heart, and kidneys. Conversion to FAD occurs primarily in the liver. FMN and FAD circulate primarily protein bound. Only small amounts ( 9%) are excreted in the urine unchanged. Larger amounts can be found after administration of large doses. 

It has been shown by the author that examination of the products excreted after administration of tryptophan to vitamin-deficient animals can give valuable information on the function of that vitamin in tryptophan metabolism (142, 171, 173). When tryptophan is given to the riboflavin-deficient rat there is a large excretion of those substances which lie to the left of line BB in diagram 19 (142, 582). This clearly indicates that this is the step at which riboflavin functions, and this is strongly supported by the fact that riboflavin deficiency can reduce up to ten-fold the conversion of tryptophan to quinolinic acid, whereas similar conversion of hydroxykynurenine is unaffected (385). On the other hand, the excretory pattern... 

Riboflavin-overproducing A. gossypii strains excrete the vitamin not only into the cultivation medium, but a significant amount is transported into the vacuole and is retained there. In contrast to S. cerevisiae or N. crassa disruption of VMAl encoding the vacuolar ATPase subunit A did not interfere with the viability of A. gossypii, but VMAl deletion mutants were devoid of any detectable vacuolar riboflavin and completely excreted the vitamin into the culture broth. ... 

The human body cannot store riboflavin, so it is excreted in the urine. For this reason, it is not dangerous to consume large doses of riboflavin, although the consumption of large amounts of the vitamin serves no biological purpose. 

Many factors affect folate metabolism, including dietary folate level, nutritional status of vitamins B6, B12, and riboflavin, zinc status, alcoholism, and physical states such as pregnancy and lactation. In many cases, the effects of these factors are seen in altered excretion rates of intact folates and metabolites, but the effects on tissue levels of the various folates and transfer rates between tissues are not well understood. Preliminary human and animal kinetic models are being devek ed in our laboratory based on studies conducted under controlled dietary conditions. These models will provide a base from which to study the effects of altered folate nutriture as well as the influence of other factors such as pregnancy and aging on folate metabolism. 

Kon and his co-workers have shown that the amount of the vitamins made available by starch refection in rats is reduced when 0.5% sulfonamides are included in the diet (Coates et al., 1946 Ford et al., 1953). There is a reduction in the amounts of thiamine and riboflavin in the tissues and excreted in the feces, and of riboflavin excreted in the urine. 

Patient with second- and third-degree burns excrete twice the normal intake of riboflavin. It is assumed that the increased excretion results from decreased use. Although the cause of such decreased use is not known, it has also been suggested that the massive nitrogen loss that occurs in extensive bums is responsible for the decreased vitamin consumption. When the bums heal, amounts of riboflavin greater than normal are needed to promote adequate cellular restoration. 

Little is known of the catabolism of riboflavin in humans, but riboflavin is a normal constituent of the urine. Therefore, all the excess vitamin could be excreted without breakdown of the molecule. The vitamin is not stored consequently, administration of excessive doses of riboflavin is accompanied by increased excretion in the urine. Riboflavin is also excreted in the milk, and the riboflavin concentration in milk reflects the vitamin intake. 

Being a water-soluble vitamin, when riboflavin intake is higher than tissue requirements, the excess is excreted in the urine, mainly as free riboflavin (6(U90%) or other metabolites, such as 7-hydroxymethylriboflavin (3-7%), 8a-sulfonylriboflavin (2-15%), 10-hydroxyethylflavin (17%), 8-hydroxy-methylriboflavin (1 %), riboflavinyl peptide ester (up to 5%), with traces of lumiflavin and, sometimes, the 10-formylmethyl- and carboxylmethylflavins (Figure 6.6). 

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