Transport and cellular uptake

Blood circulation: Transport of B6 in blood occurs as pyndoxine and pyridoxal, and as PI.P bound to albumin or other proteins. Hemoglobin becomes a significant B6-binder when pharmacological doses are ingested.

Protein-bound B6 in circulation has to be released from its carrier, and phosphate has to be hydrolyzed by phosphatases before tissues can take it up. The free pyridox-ine is taken up into liver and other tissues by a non-concentrative process, followed by metabolic trapping (phosphorylation by pyridoxal kinase, EC2.7.1.35) as PLP or PMP (Mehanshq et at., 1980).

Since many of the B6-depcndent enzymes are in the mitochondria, a mechanism must exist for the transfer of the coenzyme or of precursors across the mitochondria! membrane. No specific mechanism has been identified as yet.

Materno-fetal transfer: 1 ran sport across the placental membrane of pyridoxal is much greater than transport of pyridoxal 5'-phosphate. It has been suggested that free pyridoxal is taken up by passive transport, binding and phosphorylation in the placenta. and release to the fetal side as PLP (Schenker et ul., 1992).

Blood brain barrier. It is obvious that adequate B6 supplies are of v ita! importance for brain function, because the vitamin is needed for the synthesis andor eatabolism of many neurotransmitters (glutamate. GABA, serotonin, catecholamines, histamine, tryptamine. taurine, D-serinc, N-methyl-D-aspartate. glycine, proline). This does not even take into account numerous other B6 functions. The brain also has a very active B6 metabolism with demonstrated activities of pyridoxatnine phosphate oxidase {EC 1.4.3.5: Balm et ul., 2002) and pyridoxal kinase (EC2.7.I-35; Lee et ul.. 20(H)). Nonetheless, know ledge on the mechanisms that govern transfer of B6 into brain is lacking.

Metabolism

The ubiquitous cytosolic enzyme pyridoxal kinase (EC2.7.1.35) phosphorylates pyri-doxtne. pyridoxal. and pvridoxamine. This activity is important for two reasons: Since the transporters accept only the free forms, the phosphorvlated forms become meta-bolically trapped inside the cell. Secondly, the reaction produces PLP, the cofactor of most B6-dependent enzymes. The flavoprotein pvridoxamine phosphate oxidase (pyridoxine-5'-phosphate oxidase, ECl.4.3,5. FMN-containing) can then convert PNP and PMP into PLP. This enzyme also oxidizes pyridoxine to pyridoxal. Alternatively (Merrill ei ul.. 1984). PLP and PMP can be interconverted in liver and kidney by transamination (pyridoxamine-oxaloacetate aminotransferase. EC2.fi. 1.31). Several intracellular phosphatases cleave the phosphorvlated Bfi \ ita-mers unless they are not bound as cofactors to proteins.

In the liver, but not in muscle or erythrocytes, pyridoxal is irreversibly oxidized to the inactive metabolite 4-pyridoxic acid by FAD-dependent pyridoxamine-phosphate oxidase (EC 1.4.3,5). aldehyde dehydrogenase (AID! I: EC 1.2.1.3), or aldehyde oxidase (EC1.2.3.1, contains FAD. molybdenum cofactor, heme and additional irons arranged in a 2Fe-2S cluster).

Storage

Most of the body's B6 content, about llOmg in young men and 60mg in young women (Johansson el ul., 1966). is stored in muscle (90% of total body content)

mainly as PLP bound to Phosphorylase. B6 deficiency by itself will not promote the release ofthe vitamin from Phosphorylase (Black et a!.. 1977). but regular or accelerated (due to an energy deficit) enzyme turnover will make it available for use by other enzymes and/or tissues.

Pyridoxine in people with replete stores has an estimated half-life of 25 days (Shane. 1978).

aspar- oxaiota te acetate aspar- oxaiota te acetate

Pyridoxamine Pyridoxine phosphatase 5'-phosphate oxidase (FMN)

Pyridoxamine

Pyridoxamine Pyridoxine phosphatase 5'-phosphate oxidase (FMN)

Pyridoxal 5'-phosphate

Pyridoxamine phosphatase Pyridoxamine oxidase (FMN) 5._phosphate

Phosphatases

Pyridoxal kinase kP

Phosphatases

Pyridoxal . kinase

jf ADP ATP

H Pyridoxamine phosphatase oxidase (FMN)

Pyridoxine

Pyridoxal

Phospha tases

Pyncioxal kinase

Pyridoxamine

Pyridoxamine phosphatase oxidase (FMN)

HjfO

HsOa

4-Pyndoxic acid

Aldehyde dehydrogenase

FigurĀ» 10.26 Vitamin B6 metabolism

Understanding And Treating Autism

Understanding And Treating Autism

Whenever a doctor informs the parents that their child is suffering with Autism, the first & foremost question that is thrown over him is - How did it happen? How did my child get this disease? Well, there is no definite answer to what are the exact causes of Autism.

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