Origin of the nitrogen atom of pyridoxine in Saccharomyces cerevisiae

Tazuya, Keiko; Adachi, Yukako; Masuda, Kuniyoshi; Yamada, Kazuko; Kumaoka, Hiroshi

doi:10.1016/0304-4165(94)00205-c

Cited by 38 publications

(31 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The necessity of HMP in the medium clearly indicates that the parasite is able to create thiamine but depends on added HMP. Consistent with these results a homologue of the yeast-like Thi5 enzyme was not found in the plasmodial genome database, indicating the absence of a linkage of the vitamin B6 and B1 biosynthesis pathways (36,(53)(54)(55). Furthermore, there is no plasmodial homologue coding for the bacterial ThiC protein, the enzyme that catalyzes the formation of HMP from aminoimidazole ribonucleotide, an intermediate of purine synthesis (32).…”

Section: Does Plasmodial Vitamin B1 Biosynthesis Serve As a Target Fosupporting

confidence: 63%

Vitamin B1 and B6 in the malaria parasite: requisite or dispensable?

Wrenger

Knöckel

Walter

et al. 2008

Braz J Med Biol Res

View full text Add to dashboard Cite

Vitamins are essential compounds mainly involved in acting as enzyme co-factors or in response to oxidative stress. In the last two years it became apparent that apicomplexan parasites are able to generate B vitamers such as vitamin B1 and B6 de novo. The biosynthesis pathways responsible for vitamin generation are considered as drug targets, since both provide a high degree of selectivity due to their absence in the human host. This report updates the current knowledge about vitamin B1 and B6 biosynthesis in malaria and other apicomplexan parasites. Owing to the urgent need for novel antimalarials, the significance of the biosynthesis and salvage of these vitamins is critically discussed in terms of parasite survival and their exploitation for drug development.

show abstract

Section: Does Plasmodial Vitamin B1 Biosynthesis Serve As a Target Fosupporting

confidence: 63%

Vitamin B1 and B6 in the malaria parasite: requisite or dispensable?

Wrenger

Knöckel

Walter

et al. 2008

Braz J Med Biol Res

View full text Add to dashboard Cite

show abstract

“…The fully assembled PLP synthase complex consists of two interacting Pdx1 hexamers plus up to 12 Pdx2 molecules attached to them [9,23]. The glutaminase subunit Pdx2 generates ammoniathrough the hydrolysis of glutamine -the source of the required ring nitrogen in the synthase reaction catalyzed by Pdx1 [11,12]. Ribose 5-phosphate (R5P) and glyceraldehyde 3-phosphate (G3P) are substrates of the synthase reaction catalysed by Pdx1 along with ammonia provided by Pdx2 [13].…”

Section: Introductionmentioning

confidence: 99%

Defining the structural requirements for ribose 5‐phosphate‐binding and intersubunit cross‐talk of the malarial pyridoxal 5‐phosphate synthase

et al. 2010

View full text Add to dashboard Cite

a b s t r a c tMost organisms synthesise the B 6 vitamer pyridoxal 5-phosphate (PLP) via the glutamine amidotransferase PLP synthase, a large enzyme complex of 12 Pdx1 synthase subunits with up to 12 Pdx2 glutaminase subunits attached. Deletion analysis revealed that the C-terminus has four distinct functionalities: assembly of the Pdx1 monomers, binding of the pentose substrate (ribose 5-phosphate), formation of the reaction intermediate I 320 , and finally PLP synthesis. Deletions of distinct C-terminal regions distinguish between these individual functions. PLP formation is the only function that is conferred to the enzyme by the C-terminus acting in trans, explaining the cooperative nature of the complex.

show abstract

“…The two pathways differ in the origin of the ring nitrogen of PN that is derived from the amide group of glutamine in S. cerevisiae (39) and from glutamate in Escherichia coli (21). The two pathways also utilize different enzymes that are encoded by pdxA and pdxJ in E. coli and by the SNZ (SOR1/pyroA/PDX1/pdxS) and SNO (PDX2/pdxT/pyroB) genes in organisms that lack pdxA and pdxJ orthologues (24).…”

mentioning

confidence: 99%

Amiloride Uptake and Toxicity in Fission Yeast Are Caused by the Pyridoxine Transporter Encoded by bsu1 ⁺ ( car1 ⁺ )

2005

View full text Add to dashboard Cite

Amiloride, a diuretic drug that acts by inhibition of various sodium transporters, is toxic to the fission yeast Schizosaccharomyces pombe. Previous work has established that amiloride sensitivity is caused by expression of car1 ؉ , which encodes a protein with similarity to plasma membrane drug/proton antiporters from the multidrug resistance family. Here we isolated car1؉ by complementation of Saccharomyces cerevisiae mutants that are deficient in pyridoxine biosynthesis and uptake. Our data show that Car1p represents a new high-affinity, plasma membrane-localized import carrier for pyridoxine, pyridoxal, and pyridoxamine. We therefore propose the gene name bsu1 ؉ (for vitamin B 6 uptake) to replace car1 ؉ . Bsu1p displays an acidic pH optimum and is inhibited by various protonophores, demonstrating that the protein works as a proton symporter. The expression of bsu1 ؉ is associated with amiloride sensitivity and pyridoxine uptake in both S. cerevisiae and S. pombe cells. Moreover, amiloride acts as a competitor of pyridoxine uptake, demonstrating that both compounds are substrates of Bsu1p. Taken together, our data show that S. pombe and S. cerevisiae possess unrelated plasma membrane pyridoxine transporters. The S. pombe protein may be structurally related to the unknown human pyridoxine transporter, which is also inhibited by amiloride.Vitamin B 6 is a generic term describing a group of three water-soluble vitamins, pyridoxine (PN), pyridoxal (PL), and pyridoxamine (PM), and the 5Ј-phosphates derived therefrom. Vitamin B 6 is synthesized in plants and most microorganisms but cannot be produced by mammals and thus represents an essential component of the human diet.Vitamin B 6 has a central role in the metabolism of amino acids. PL phosphate (PLP) is the cofactor of amino acid transaminases and decarboxylases and enzymes involved in elimination and replacement reactions (19). A more recently discovered function of vitamin B 6 is protection from reactive oxygen species: PN and PLP are as effective as the well-established antioxidant vitamins C and E in quenching singlet oxygen species (6, 10). Moreover, vitamin B 6 is an intermediate in the synthesis of thiamine (vitamin B 1 ). This metabolic pathway is best known for S. cerevisiae cells, where the pyrimidine moiety of thiamine derives from histidine and PN (reference 49 and references therein). The S. cerevisiae THI5 and THI20 gene families are involved in this pathway (44), and both families have orthologues in many other yeast species. Thus, the yeast thiamine biosynthetic pathway is different from the pathway found in many prokaryotes, where PN is not used as a precursor (43). In addition to having evolved different strategies to synthesize the pyrimidine unit of thiamine, synthesis of the thiazole moiety also follows different routes in pro-and eukaryotes (43).To date, two different pathways for PN biosynthesis have been described. The two pathways differ in the origin of the ring nitrogen of PN that is derived from the amide group of glutamine in S. cer...

show abstract

Origin of the nitrogen atom of pyridoxine in Saccharomyces cerevisiae

Cited by 38 publications

References 9 publications

Vitamin B1 and B6 in the malaria parasite: requisite or dispensable?

Vitamin B1 and B6 in the malaria parasite: requisite or dispensable?

Defining the structural requirements for ribose 5‐phosphate‐binding and intersubunit cross‐talk of the malarial pyridoxal 5‐phosphate synthase

Amiloride Uptake and Toxicity in Fission Yeast Are Caused by the Pyridoxine Transporter Encoded by bsu1 ⁺ ( car1 ⁺ )

Contact Info

Product

Resources

About

Origin of the nitrogen atom of pyridoxine in Saccharomyces cerevisiae

Cited by 38 publications

References 9 publications

Vitamin B1 and B6 in the malaria parasite: requisite or dispensable?

Vitamin B1 and B6 in the malaria parasite: requisite or dispensable?

Defining the structural requirements for ribose 5‐phosphate‐binding and intersubunit cross‐talk of the malarial pyridoxal 5‐phosphate synthase

Amiloride Uptake and Toxicity in Fission Yeast Are Caused by the Pyridoxine Transporter Encoded by bsu1 + ( car1 + )

Contact Info

Product

Resources

About

Amiloride Uptake and Toxicity in Fission Yeast Are Caused by the Pyridoxine Transporter Encoded by bsu1 ⁺ ( car1 ⁺ )