Blood biotin transport

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 activity in cerebrospinal fluid and the brain is very low. This suggests that the brain may not recycle biotin effectively and depends on biotin transported across the blood-brain barrier. Several symptomatic children who have failed to exhibit peripheral lactic acidosis or organic aciduria have had elevated lactate or organic acids in their cerebrospinal fluid. This compartmentalization of the biochemical abnormalities may explain why the neurological symptoms usually appear before other symptoms. Peripheral metabolic ketoacidosis and organic aciduria subsequently occur with prolonged metabolic compromise. 

Vlasova, T.I., Stratton, S.L., Wells, A.M., Mock, N.I., and Mock, D.M., 2005. Biotin deficiency reduces expression of SLC19A3, a potential biotin transporter, in leukocytes from human blood. The Journal of Nutrition. 135 42-47. 

Biotin is essential for cell proliferation. Peripheral blood mononuclear cells appear to take up biotin by a system that is distinct from the sodium-dependent multivitamin transporter that is responsible for intestinal and renal uptake of biotin (Section 11.1). In response to mitogenic stimuli the uptake of biotin increases several-fold, with no change in the activity of the sodium-dependent transporter. At the same time, there is an increase in the rate of expression of methylcrotonyl CoA, propionyl CoA carboxylases, and holocarboxylase... 

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. 

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),... 

B. This compound is acetoacetate, which is synthesized in the liver when blood insulin levels are low. HMG CoA synthetase is the key regulatory enzyme for synthesis, not oxidation. Acetoacetate is transported to tissues, such as muscle, where it is activated in the mitochondrion by succinyl CoA (not ATP), cleaved to 2 acetyl CoA, and oxidized via the TCA cycle, which requires the vitamin thiamine as thiamine pyrophosphate, a cofactor for a-ketoglutarate dehydrogenase. Biotin is not required. 

Biotin is transported across the blood-brain barrier. The transporter is saturable and structurally specific for the free carboxylate group on the valeric acid side chain. Transport into the neuron also appears to involve a specific transport system with subsequent trapping of biotin by covalent binding to brain proteins, presumably carboxylases. 

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