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a salt of phosphoric acid (同)orthophosphate, inorganic_phosphate
carbonated drink with fruit syrup and a little phosphoric acid

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〈U〉リン酸塩 / 《複数形で》リン酸肥料

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/06/15 00:44:14」(JST)

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Pyridoxamine is one form of vitamin B₆. Chemically it is based on a pyridine ring structure, with hydroxyl, methyl, aminomethyl, and hydroxymethyl substituents. It differs from pyridoxine by the substituent at the 4-position. The phenol at position 3 and aminomethyl group at position 4 of its ring endow pyridoxamine with a variety of chemical properties, including the scavenging of free radical species and carbonyl species formed in sugar and lipid degradation and chelation of metal ions that catalyze Amadori reactions.^[1]

Research

Pyridoxamine can form fairly weak complexes with a number of transition metal ions, with a preference for Cu²⁺ and Fe³⁺.^[2] The 3'-hydroxyl group of pyridoxamine allows for efficient hydroxyl radical scavenging.^[2]

Pyridoxamine inhibits the Maillard reaction and can block the formation of advanced glycation endproducts,^[3] which are associated with medical complications of diabetes.^[4] Pyridoxamine is hypothesized to trap intermediates in the formation of Amadori products released from glycated proteins, possibly preventing the breakdown of glycated proteins by disrupting the catalysis of this process through disruptive interactions with the metal ions crucial to the redox reaction.^[5] One research study found that pyridoxamine specifically reacts with the carbonyl group in Amadori products, but inhibition of post-Amadori reactions (that can lead to advanced glycation endproducts) is due in much greater part to the metal chelation effects of pyridoxamine.^[1]

A variety of preclinical studies in animal models of diabetes indicated that pyridoxamine improved kidney histology comparable or superior to aminoguanidine.^[5] Because of these results, pyridoxamine has been investigated for clinical utility in the treatment of diabetic nephropathy.^[5]^[6]

Pyridoxamine also inhibits the formation of advanced lipoxidation endproducts during lipid peroxidation reactions by reaction with dicarbonyl intermediates.^[7] In other preclinical research, pyridoxamine may be efficacious in treating diabetic neuropathy and retinopathy associated with diabetes^[5]^[7] and kidney stone disease.^[2] In one study, pyridoxamine was more effective at protecting from ionizing radiation-induced gastrointestinal epithelial apoptosis than amifostine (the only radioprotector currently Food and Drug Administration (FDA)-approved) due to pyridoxamine reactive oxygen species and reactive carbonyl species scavenging profile.^[8]

FDA Regulatory Activity

Pyridoxamine was marketed as a dietary supplement, often as the hydrochloride salt, pyridoxamine dihydrochloride. However, in the United States, the FDA ruled in January 2009 that pyridoxamine must be regulated as a pharmaceutical drug because it is the active ingredient in Pyridorin, a drug designed by Biostratum, Inc., to prevent the progression of diabetic nephropathy.^[9]^[10]^[11]^[12]

Pyridorin had success in early clinical trials, found to be effective in slowing the progression of diabetic neuropathy in a phase II trial on 224 patients.^[10] However, in 2005 Biostratum ran out of money and so was unable to begin a Phase III trial.^[10] Investors in Biostratum had realized that because Biostratum had no patent on pyridoxamine itself, and that pyridoxamine was commonly available for purchase as a dietary supplement, the company would be unable to charge enough money for the treatment (should it be approved as a prescription drug by the FDA) for the investors to get a reasonable return on the investment they had already made (about $100M) much less on the additional investment a Phase III trial would require.^[10] To solve this problem, Biostratum submitted a Citizen Petition to the FDA on July 29, 2005, seeking to disallow sales of pyridoxamine-containing supplements on the grounds that pyridoxamine, as the subject of an Investigational New Drug Application with the FDA, is a drug and not a dietary supplement.^[10] This petition was opposed by the Council for Responsible Nutrition, a trade association of the dietary supplement industry.^[10]

On January 12, 2009, the FDA ruled that products containing pyridoxamine are excluded from the definition of dietary supplements as defined by the Dietary Supplement Health and Education Act of 1994.^[11] The FDA stated that the status of Pyridorin as an investigational new drug, as a result of an application filed by BioStratum in July 1999 and effective on September 1, 1999, meant that "the marketing of pyridoxamine in a dietary supplement is essentially equivalent to the marketing of an investigational new drug as a dietary supplement" because there was an "absence of independent, verifiable evidence that the substance was marketed as a food or a dietary supplement prior to its authorization for investigation as a new drug."^[13]

In 2006, Biostratum licensed its rights in Pyridorin to another company, NephroGenex ^[14] In 2008, NephroGenex restarted the clinical development of Pyridorin, which as of 2012 is still ongoing.^[15]

Patenting Activity

A patent application claiming pharmaceutical compositions of pyridoxamine, and methods to use pyridoxamine to treat diabetic complications, was filed by Biostratum and was published in 2004.^[16] The application does not claim pyridoxamine itself.

References

^ ^a ^b Adrover M, Vilanova B, Frau J, Muñoz F, Donoso J (May 2008). "The pyridoxamine action on Amadori compounds: A reexamination of its scavenging capacity and chelating effect". Bioorg. Med. Chem. 16 (10): 5557–69. doi:10.1016/j.bmc.2008.04.002. PMID 18434162.
^ ^a ^b ^c Voziyan PA, Hudson BG (2005). "Pyridoxamine as a multifunctional pharmaceutical: targeting pathogenic glycation and oxidative damage". Cell. Mol. Life Sci. 62 (15): 1671–81. doi:10.1007/s00018-005-5082-7. PMID 15905958.
^ Voziyan PA, Hudson BG (2005). "Pyridoxamine: the many virtues of a maillard reaction inhibitor". Ann. N. Y. Acad. Sci. 1043 (1): 807–16. doi:10.1196/annals.1333.093. PMID 16037308.
^ Ahmed N, Thornalley PJ (2007). "Advanced glycation endproducts: what is their relevance to diabetic complications?". Diabetes Obes Metab 9 (3): 233–45. doi:10.1111/j.1463-1326.2006.00595.x. PMID 17391149.
^ ^a ^b ^c ^d Giannoukakis N (2005). "Pyridoxamine (BioStratum)" (PDF). Curr Opin Investig Drugs 6 (4): 410–8. PMID 15898348.
^ Williams ME, Bolton WK, Khalifah RG, Degenhardt TP, Schotzinger RJ, McGill JB (2007). "Effects of pyridoxamine in combined phase 2 studies of patients with type 1 and type 2 diabetes and overt nephropathy". Am. J. Nephrol. 27 (6): 605–14. doi:10.1159/000108104. PMID 17823506.
^ ^a ^b Metz TO, Alderson NL, Thorpe SR, Baynes JW (2003). "Pyridoxamine, an inhibitor of advanced glycation and lipoxidation reactions: a novel therapy for treatment of diabetic complications". Arch. Biochem. Biophys. 419 (1): 41–9. doi:10.1016/j.abb.2003.08.021. PMID 14568007.
^ Thotala D, Chetyrkin S, Hudson B, Hallahan D, Voziyan P, Yazlovitskaya E (September 2009). "Pyridoxamine protects intestinal epithelium from ionizing radiation-induced apoptosis". Free Radic. Biol. Med. 47 (6): 779–85. doi:10.1016/j.freeradbiomed.2009.06.020. PMC 2739572. PMID 19540915.
^ "FDA finds vitamin B6 form not legal in supplements", newsfood.com, February 2, 2009
^ ^a ^b ^c ^d ^e ^f "Big problem for BioStratum", Triangle Business Journal, October 14, 2005
^ ^a ^b "FDA's pyridoxamine decision: FDA's decision regarding pyridoxamine has larger implications for dietary ingredients in general", Entrepreneur, April, 2009
^ http://www.regulations.gov/#!documentDetail;D=FDA-2005-P-0259-0004
^ FDA-2005-P-0259-0004: FDA Response to Biostratum, Inc. (Kathleen M Sanzo, Esq) - Petition Partial Approved and Denial
^ http://www.renalbusiness.com/news/2006/05/nephrogenex-acquires-rights-to-diabetic-nephropat.aspx
^ http://www.nephrogenex.com/NGX_News.htm
^ (WO/2004/112788) PYRIDOXAMINE FOR THE TREATMENT OF DIABETIC KIDNEY DISEASE, World Intellectual Property Organization

External links

Clinical trials testing Pyridoxamine (clinicaltrials.gov):
- Effect of Pyridorin in Patients With Diabetic Nephropathy (NCT00320060)
- Effect of Pyridorin in Patients With Diabetic Nephropathy (NCT00320021)
- Safety and Efficacy Study of Pyridorin in Patients With Nephropathy Due to Type 2 Diabetes (NCT00734253)

UpToDate Contents

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1. カルシウムおよびリン酸バランスの調節 regulation of calcium and phosphate balance
2. 高リン血症の原因および治療の概要 overview of the causes and treatment of hyperphosphatemia
3. グルコース-6-リン酸脱水素酵素欠損症の診断および治療 diagnosis and treatment of glucose 6 phosphate dehydrogenase deficiency
4. 慢性腎疾患における高リン血症の治療 treatment of hyperphosphatemia in chronic kidney disease
5. 低リン血症の評価および治療 evaluation and treatment of hypophosphatemia

English Journal

The structure of NtdA, a sugar aminotransferase involved in the kanosamine biosynthetic pathway in Bacillus subtilis, reveals a new subclass of aminotransferases.

van Straaten KE, Ko JB, Jagdhane R, Anjum S, Palmer DR, Sanders DA.Author information From the Department of Chemistry, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5C9, Canada.AbstractNtdA from Bacillus subtilis is a sugar aminotransferase that catalyzes the pyridoxal phosphate-dependent equatorial transamination of 3-oxo-α-D-glucose 6-phosphate to form α-D-kanosamine 6-phosphate. The crystal structure of NtdA shows that NtdA shares the common aspartate aminotransferase fold (Type 1) with residues from both monomers forming the active site. The crystal structures of NtdA alone, co-crystallized with the product α-D-kanosamine 6-phosphate, and incubated with the amine donor glutamate reveal three key structures in the mechanistic pathway of NtdA. The structure of NtdA alone reveals the internal aldimine form of NtdA with the cofactor pyridoxal phosphate covalently attached to Lys-247. The addition of glutamate results in formation of pyridoxamine phosphate. Co-crystallization with kanosamine 6-phosphate results in the formation of the external aldimine. Only α-D-kanosamine 6-phosphate is observed in the active site of NtdA, not the β-anomer. A comparison of the structure and sequence of NtdA with other sugar aminotransferases enables us to propose that the VIβ family of aminotransferases should be divided into subfamilies based on the catalytic lysine motif.
The Journal of biological chemistry.J Biol Chem.2013 Nov 22;288(47):34121-30. doi: 10.1074/jbc.M113.500637. Epub 2013 Oct 4.
NtdA from Bacillus subtilis is a sugar aminotransferase that catalyzes the pyridoxal phosphate-dependent equatorial transamination of 3-oxo-α-D-glucose 6-phosphate to form α-D-kanosamine 6-phosphate. The crystal structure of NtdA shows that NtdA shares the common aspartate aminotransferase fold (T
PMID 24097983

Crystal structure of Saccharomyces cerevisiae Aro8, a putative α-aminoadipate aminotransferase.

Bulfer SL, Brunzelle JS, Trievel RC.Author information Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan, 48109.Abstractα-Aminoadipate aminotransferase (AAA-AT) catalyzes the amination of 2-oxoadipate to α-aminoadipate in the fourth step of the α-aminoadipate pathway of lysine biosynthesis in fungi. The aromatic aminotransferase Aro8 has recently been identified as an AAA-AT in Saccharomyces cerevisiae. This enzyme displays broad substrate selectivity, utilizing several amino acids and 2-oxo acids as substrates. Here we report the 1.91Å resolution crystal structure of Aro8 and compare it to AAA-AT LysN from Thermus thermophilus and human kynurenine aminotransferase II. Inspection of the active site of Aro8 reveals asymmetric cofactor binding with lysine-pyridoxal-5-phosphate bound within the active site of one subunit in the Aro8 homodimer and pyridoxamine phosphate and a HEPES molecule bound to the other subunit. The HEPES buffer molecule binds within the substrate-binding site of Aro8, yielding insights into the mechanism by which it recognizes multiple substrates and how this recognition differs from other AAA-AT/kynurenine aminotransferases.
Protein science : a publication of the Protein Society.Protein Sci.2013 Oct;22(10):1417-24. doi: 10.1002/pro.2315. Epub 2013 Aug 28.
α-Aminoadipate aminotransferase (AAA-AT) catalyzes the amination of 2-oxoadipate to α-aminoadipate in the fourth step of the α-aminoadipate pathway of lysine biosynthesis in fungi. The aromatic aminotransferase Aro8 has recently been identified as an AAA-AT in Saccharomyces cerevisiae. This enzym
PMID 23893908

Crystal structure and functional studies of an unusual L-cysteine desulfurase from Archaeoglobus fulgidus.

Yamanaka Y, Zeppieri L, Nicolet Y, Marinoni EN, de Oliveira JS, Odaka M, Dean DR, Fontecilla-Camps JC.Author information Department of Biotechnology and Life Science Graduate School of Technology, Tokyo University of Agriculture and Technology, Tokyo, Japan.AbstractL-Cysteine desulfurase IscS and scaffold IscU proteins are universally involved in Fe/S cluster synthesis. The Archaeoglobus fulgidus (Af) genome encodes proteins having a high degree of primary structure similarity to IscS and IscU from other organisms. However, AfIscS is unusual because it lacks the active site lysine residue that normally forms an internal Schiff base with pyridoxal-phosphate (PLP) and serves as a base during catalysis. Our as-isolated recombinant AfIscS contains pyridoxamine phosphate (PMP) instead of the expected PLP and lacks desulfurase activity. We have solved its structure to 1.43 Å resolution and found that PMP binds non-covalently at the PLP site of the enzyme and displays significant disorder. However, the previously reported structure of recombinant Af(IscU-D35A-IscS)(2) contains an in vivo generated [Fe(2)S(2)] species within AfIscU and the question arises as to how its sulfides were generated. Here, we report that adding PLP to AfIscS produces an enzyme that displays in vitro L-cysteine desulfurase activity mediating the synthesis of a stable holo Af(IscU-D35A-IscS) complex.
Dalton transactions (Cambridge, England : 2003).Dalton Trans.2013 Mar 7;42(9):3092-9. doi: 10.1039/c2dt32101g. Epub 2012 Nov 19.
L-Cysteine desulfurase IscS and scaffold IscU proteins are universally involved in Fe/S cluster synthesis. The Archaeoglobus fulgidus (Af) genome encodes proteins having a high degree of primary structure similarity to IscS and IscU from other organisms. However, AfIscS is unusual because it lacks t
PMID 23160436

Japanese Journal

Contents of All Forms of Vitamin B₆, Pyridoxine-β-Glucoside and 4-Pyridoxic Acid in Mature Milk of Japanese Women According to 4-Pyridoxolactone-Conversion High Performance Liquid Chromatography

, , [他], ,
Journal of Nutritional Science and Vitaminology 59(1), 9-15, 2013
… Pyridoxal and pyridoxal 5′-phosphate were found in all of the samples, and their average contents were 0.71±0.28 (μmol/L) and 0.16±0.07 (μmol/L), respectively. … Pyridoxamine, pyridoxine, pyridoxamine 5'-phosphate, pyridoxine 5'-phosphate, and pyridoxine-β-glucoside were found in 15, 14, 13, 9, and 7 samples, respectively. … The presence of pyridoxine 5'-phosphate was for the first time found in human milk. …
NAID 130003368153

ビタミンB_6測定法の現状と課題(<特集>ビタミン測定法の現状と課題[I])

八木年晴
ビタミン 85(3), 116-126, 2011-03-25
… Natural vitamin B_6 consists of six compounds which are pyridoxine, pyridoxal, pyridoxamine, pyridoxine 5'-phosphate, pyridoxal 5'-phosphate, and pyridoxamine 5'-phosphate. …
NAID 110008607855

Isolation and characterization of vitamin B6-producing thermophilic bacterium, Geobacillus sp. H6a

, , ,
The Journal of General and Applied Microbiology 56(3), 273-279, 2010
NAID 130004802182

Related Pictures

★リンクテーブル★

リンク元	「ピリドキサミンリン酸」「リン酸ピリドキサミン」
拡張検索	「pyridoxamine phosphate oxidase」
関連記事	「phosphate」

「ピリドキサミンリン酸」

Pyridoxamine
Names
	IUPAC name 4-(aminomethyl)-5-(hydroxymethyl)-2-methylpyridin-3-ol
Identifiers
CAS Registry Number	85-87-0
ChEBI	CHEBI:16410
ChEMBL	ChEMBL593019
ChemSpider	1023
	InChI InChI=1S/C8H12N2O2/c1-5-8(12)7(2-9)6(4-11)3-10-5/h3,11-12H,2,4,9H2,1H3 ; Key: NHZMQXZHNVQTQA-UHFFFAOYSA-N ; InChI=1/C8H12N2O2/c1-5-8(12)7(2-9)6(4-11)3-10-5/h3,11-12H,2,4,9H2,1H3; Key: NHZMQXZHNVQTQA-UHFFFAOYAS ;
Jmol-3D images	Image
KEGG	C00534
PubChem	1052
	SMILES Oc1c(c(cnc1C)CO)CN ;
Properties
Chemical formula	C8H12N2O2
Molar mass	168.20 g·mol−1
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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	Infobox references