Biotin plasma concentration

The affected infants have a normal plasma concentration of biotin and excrete normal amounts of biotin in the urine. Skin fibroblasts have extremely low activities of aU four biotin-dependent carboxylases when they are cultured in media containing approximately physiological concentrations of biotin. But, culture with considerably higher concentrations of biotin results in normal activity of aU four carboxylases. The defect is in the affinity of holocarboxylase synthetase for biotin (its is 20- to 70-fold higher than normal). 

The plasma concentration of the biotin does not provide a sensitive index of stams, at least partly because there is increased renal reabsorption of the vitamin as intake falls. Urinary excretion of biotin and its metabolites is more sensitive, but may be confounded by changes in biotin excretion caused by glucocorticoid hormones (McMahon, 2002). There are three sensitive markers of stams (Mock, 1999) ... 

The activity of propionyl CoA carboxylase in lymphocytes falls, and the activation of the apoenzyme on incubation with biotin rises, in patients receiving total parenteral nutrition before there is any change in the plasma concentration of biotin (Velazquez et al., 1990). In experimental animals, the activity of lymphocyte propionyl CoA carboxylase falls early during biotin depletion, at the same time as the activity of the hepatic enzyme. There is not the expected increase in urinary excretion of hydroxypropionic acid, presumably because propionyl CoA carboxylase is not rate-limiting for propionate metabolism (Mock and Mock, 2002). 

Reduced activity of methylcrotonyl CoA carboxylase (Section 11.2.1.4) results in the formation and excretion of 3-hydroxy-isovaleric acid in experimental biotin depletion, significant amounts of 3-hydroxy-isovaleric acid are excreted at the same time as the excretion of biotin and bisnorbiotin falls, before there is any change in the plasma concentration of biotin (Mock et al., 1997). 

The RDA for biotin has not been established. The requirement for biotin has been established as 30 to 100 pg/day. Biotin is produced by the gut microflora, which, it has been estimated, supplies half of our requirement. The rate of transport of free biotin by the gut cell is higher in the jejunum than in the ileum and is very low in the colon. Despite the low level of transport in the colon, it is apparently sufficient to allow supply by vitamin produced in the gut. The digestion of dietary proteins results in the release of the constituent amino acids and of biotin in the form of lysyl-biotin. Lysyl-biotin is further cleaved to lysine and biotin by biotinidase, an enzyme of the gut mucosa. The enzyme is present in milk and in the bloodstream as well, Biotin in human blood plasma occurs at a concentration of about 4 nM (Velazquez ef /, 1995). Nearly all of the biotin in human milk is free and not bound to proteins. Breast milk contains biotin at concentrations of about 25 nM (MiKik et al., 1997a),... 

Vitamin requirements for ESKD patients receiving dialysis differ from those of a healthy person because of dietary modifications, kidney dysfunction, and dialysis therapy. The plasma concentrations of vitamins A and E are elevated in ESKD, while those of the water-soluble vitamins (81,82,8g, 812, niacin, pantothenic acid, folic acid, biotin, and vitamin C) tend to be low in this population, in large part due to the fact that many are dialyzable. The goal for vitamin supplementation in this population should be to prevent subclinical and frank deficiency and to avoid pathology from overdosage. Special vitamin supplements have been formulated for the dialysis population, which primarily include 8 vitamins with C and folic acid. 

In a single study, plasma concentrations of free biotin decreased to abnormal values in only half of the subjects. This observation provides confirmation... 

Biotinidase activity in plasma is quantitated by a simple colorimetric assay that uses the artificial substrate B-PABA. Biotinidase cleaves the amide bond of B-PABA forming free biotin and p-aminobenzoic acid (PABA). PABA is then converted to a purple azo dye and quantitated spectrophotometrically. No colour develops when biotinidase is inactive. Biotinidase with reduced affinity for the substrate (Km variant) can be detected by simultaneous assay of the activity with two substrate concentrations, a saturating standard concentration of 0.15 mM and a ten-times higher concentration of 1.5 mM [26]. Greater than 1.2 times higher activity with the higher substrate concentration indicates a Km defect. 

Plasma biotin concentrations may be deficient in patients with biotinidase deficiency, but also can be normal prior to therapy. Again, it is important to be certain that the method used to determine the biotin concentration measures free biotin and does not also measure biotin derivatives, such as biocytin. 

Two children with the late-onset form initially were reported as having a defect in intestinal transport of biotin. This conclusion was supported by finding low plasma biotin concentrations when these children were administered oral biotin compared to the concentrations of plasma biotin of unaffected control subject. In 1983, it was demonstrated that the primary biochemical defect in most patients with late-onset multiple carboxylase deficiency was a deficiency of serum biotinidase activity. The two children with a putative defect in intestinal biotin transport both were confirmed to have biotinidase deficiency. This disparity was reconciled by demonstrating that, in both cases, the children were biotin depleted at the time the biotin-loading studies were performed. Therefore, when the children initially were given biotin, although the vitamin was transported into the blood normally, it was rapidly taken up... 

Biotinidase is also the major plasma binding protein for biotin. The pH optimum of the enzyme is 4.5 to 5.5, and its is in the micromolar range, compared with the nanomolar concentrations of biocytin, so it will have little enzymic activity in plasma. Rather, it functions as a transport protein for biotin, preventing its urinary excretion children with biotinidase deficiency (Section 11.2.3.1) excrete large amounts of both biocytin and free biotin. Biotin is covalently bound to biotinidase in plasma, as a thioester to a cysteine residue in the active site of the enzyme (see Figure 11.1). This thioester is formed only from biocytin, not free biotin, and is presumably the (normally transient)... 

Biotin forms part of several enzyme systems and is necessary for normal growth and body function. Biotin functions as a cofactor for enzymes involved in carbon dioxide fixation and transfer. These reactions are important in the metaboHsm of carbohydrates, fats, and proteins, as well as promotion of the synthesis and formation of nicotinic acid, fatty acids, glycogen, and amino acids (5—7). Biotin is absorbed unchanged in the upper part of the small intestine and distributed to all tissues. Highest concentrations are found in the Hver and kidneys. Little information is available on the transport and storage of biotin in humans or animals. A biotin level in urine of approximately 160 nmol/24 h or 70 nmol/L, and a circulating level in blood, plasma, or serum of approximately 1500 pmol/L seems to indicate an adequate supply of biotin for humans. However, reported levels for biotin in the blood and urine vary widely and are not a reHable indicator of nutritional status. 

At higher ethanol concentrations the intracellular alcohol interferes with membrane organization, increasing its fluidity and permeability to ions and small metabolites and inhibiting transport of nutrients. Especially Ca and Mg ions are able to increase the plasma membrane stability. It has been demonstrated that incorporation of unsaturated fatty acids and/or sterol(s) as well as proteolipids into cellular membrane of yeasts helps to alleviate ethanol tolerance. For the synthesis of the unsaturated fatty acids the presence of traces of oxygen under fermentation conditions is required. Further to Ca and Mg ions, other trace elements such as Co, Cu, Mn and Zn " and vitamins, e.g. pantothenate, thiamine, riboflavin, nicotinic acid, pyridoxine, biotin, folic acid and inositol, are essential for the growth and ethanol production by yeasts. 

A negative correlation between deficient biotin status and blood lipid concentrations was found in rats (Marshall et al. 1976) as well as in humans (Marshall et al. 1980). A decrease in plasma lipids was observed in human healthy volunteers within 30 min of absorption of 100 mg of biotin infusion. It was shown that oral biotin supplementation affected plasma lipid concentrations. The administration of 5 mg/day of biotin decreased hypercholesterolemia in atherosclerosis and hyperlipidemia patients (Dukusova and Krivoruchenko 1972). A 15 mg/day treatment by biotin for 28 days decreased hypertriglyceridemia of subjects whose triacylglycerol concentrations were more than 25% above the normal of 1.8mmol/L (Baez-Saldana 2004). 

Biotin concentrations are 3- to 17-fold greater in plasma from human fetuses compared to those in their mothers in the second trimester, consistent with active placental transport. The microvillus membrane of the placenta contains a saturable transport system for biotin that is Na dependent and actively accumulates biotin within the placenta, consistent with SMVT. 

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