Fosforibozylpyrofosfát

	Fosforibozylpyrofosfát
	Fosforibozylpyrofosfát
	Všeobecné vlastnosti
Sumárny vzorec	C5H13O14P3
Synonymá	(2R,3R,4S,5R)-3,4-Dihydroxy-5-oxolán-2-yltrihydrogéndifosforečnan, 5-fosforibozyl-1-difosfát, 5-fosforibozyl-1-pyrofosfát, PRPP, fosforibozyldifosfát,
	Fyzikálne vlastnosti
Molárna hmotnosť	390,07 g/mol
	Ďalšie informácie
Číslo CAS	7540-64-9
	Pokiaľ je to možné a bežné, používame jednotky sústavy SI. ; Ak nie je hore uvedené inak, údaje sú za normálnych podmienok.
	Chemický portál

Fosforibozylpyrofosfát (PRPP, tiež 5-fosforibozyl-1-difosfát) je pentózafosfát, ktorý vystupuje ako biochemický intermediát v biosyntéze purínových nukleotidov. Tvoria sa z neho teda stavebné bloky DNA a RNA.^[1]^[2]^[3] Vitamíny tiamín^[4] a kobalamín^[5] takisto obsahujú fragmenty, ktoré sú odvodené od PRPP. PRPP tiež vystupuje v biosyntéze aminokyselín histidínu a tryptofánu.^[6] Skladá sa z pentózy ribózy a troch fosfátových skupín, jednej viazanej na C5 uhlík a dvoch viazaných v podobe pyrofosfátu na C1 uhlík.

Syntéza

PRPP vzniká z ribóza-5-fosfátu (R5P) pôsobením enzýmu ribózafosfátdifosfokinázy, ktorá katalyzuje nasledujúcu reakciu:^[7]

Úloha PRPP v metabolizme

PRPP vystupuje v niekoľkých reakciách, pri ktorých sa prenáša fosforibózová skupina, vrátane obnovovacích dráh:^[8]

Enzým	Reaktant	Produkt
adenínfosforibozyltransferáza	adenín	AMP^[9]
hypoxantín-guanínfosforibozyltransferáza	guanín	GMP^[10]
hypoxantín-guanínfosforibozyltransferáza	hypoxantín	IMP^[10]
nikotinátfosforibozyltransferáza	nikotinát	nikotinátribozid^[11]
orotátfosforibozyltransferáza	orotát	OMP^[12]
uracilfosforibozyltransferáza	uracil	UMP^[13]
xantínfosforibozyltransferáza	xantín	XMP^[14]

Pri de novo syntéze purínov pôsobí enzým amidofosforibozyltransferáza na PRPP, čím vzniká fosforibozylamín.^[2]

Pri biosyntéze histidínu dochádza k reakcii PRPP s ATP, pri ktorej sa štiepi kruh ATP. Uhlíkové atómy z ribózy v PRPP tvoria lineárny reťazec a časť imidazolového kruhu histidínu.^[15]^[16]^[17] To isté platí pre biosyntézu tryptofánu, kde prvým krokom je N-alkylácia kyseliny antranilovej katalyzovaná enzýmom antranilátfosforibozyltransferázou.^[15]^[18]^[19]

Zvýšená hladina PRPP

Zvýšená hladina PRPP je charakterizovaná zvýšenou produkciou a akumuláciou kyseliny močovej, čo vedie k hyperurikémii a hyperurikozúrii. Je to jedna z príčin vzniku dny.^[20]

Zvýšená hladina PRPP je takisto prítomná pri Lesch–Nyhanovom syndróme. Spôsobuje to znížená hladina hypoxantín-guanínfosforibozyltransferázy (HGPRT), keďže PRPP je substrát tohto enzýmu počas obnovovania purínov.^[21]

Referencie

↑ R. Caspi. Pathway: 5-aminoimidazole ribonucleotide biosynthesis I . MetaCyc Metabolic Pathway Database, 2009-01-13. Dostupné online.
↑ ^a ^b Structural biology of the purine biosynthetic pathway. Cellular and Molecular Life Sciences, 2008, s. 3699–3724. DOI: 10.1007/s00018-008-8295-8.
↑ GUPTA, Rani; GUPTA, Namita. Fundamentals of Bacterial Physiology and Metabolism. : , 2021. ISBN 978-981-16-0722-6. DOI:10.1007/978-981-16-0723-3_19 Nucleotide Biosynthesis and Regulation, s. 525–554.
↑ A "Radical Dance" in Thiamin Biosynthesis: Mechanistic Analysis of the Bacterial Hydroxymethylpyrimidine Phosphate Synthase. Angewandte Chemie International Edition, 2010, s. 8653–8656. DOI: 10.1002/anie.201003419. PMID 20886485.
↑ R. Caspi. Pathway: 5-hydroxybenzimidazole biosynthesis (anaerobic) . MetaCyc Metabolic Pathway Database, 2019-09-23. Dostupné online.
↑ MEHTA, Angad P.; ABDELWAHED, Sameh H.; FENWICK, Michael K.. Anaerobic 5-Hydroxybenzimidazole Formation from Aminoimidazole Ribotide: An Unanticipated Intersection of Thiamin and Vitamin B12 Biosynthesis. Journal of the American Chemical Society, 2015-08-26, roč. 137, čís. 33, s. 10444–10447. Dostupné online . ISSN 0002-7863. DOI: 10.1021/jacs.5b03576.
↑ Crystal structure of human phosphoribosylpyrophosphate synthetase 1 reveals a novel allosteric site. Biochemical Journal, January 2007, s. 39–47. DOI: 10.1042/BJ20061066. PMID 16939420.
↑ R. Caspi. 5-phospho-α-D-ribose 1-diphosphate . MetaCyc Metabolic Pathway Database, 2022-02-15. Dostupné online.
↑ Structural Complexes of Human Adenine Phosphoribosyltransferase Reveal Novel Features of the APRT Catalytic Mechanism. Journal of Biomolecular Structure and Dynamics, 2008, s. 589–597. DOI: 10.1080/07391102.2008.10507205. PMID 18399692.
↑ ^a ^b Mutational spectral analysis at the HPRT locus in healthy children. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 2002, s. 27–41. DOI: 10.1016/S0027-5107(02)00119-7. PMID 12175903.
↑ A new paradigm for biochemical energy coupling. Salmonella typhimurium nicotinate phosphoribosyltransferase. Journal of Biological Chemistry, 1993, s. 26004–26010. DOI: 10.1016/S0021-9258(19)74485-8. PMID 7503993.
↑ Ternary Complex Formation and Induced Asymmetry in Orotate Phosphoribosyltransferase. Biochemistry, 2007, s. 14075–14086. DOI: 10.1021/bi701023z. PMID 18020427.
↑ Dynamic dissociating homo-oligomers and the control of protein function. Archives of Biochemistry and Biophysics, 2012, s. 131–143. DOI: 10.1016/j.abb.2011.11.020. PMID 22182754.
↑ Guanine and Xanthine Phosphoribosyltransfer Activities of Lactobacillus casei and Escherichia coli. Journal of Biological Chemistry, 1970, s. 2605–2611. DOI: 10.1016/S0021-9258(18)63113-8.
↑ ^a ^b VOET, Donald. Fundamentals of biochemistry : life at the molecular level. Hoboken, NJ : , 2016. (Fifth edition.) Dostupné online. ISBN 978-1-118-91840-1.
↑ R. Caspi. Pathway: L-histidine biosynthesis . MetaCyc Metabolic Pathway Database, 2008-10-10. Dostupné online.
↑ Histidine biosynthesis in plants. Amino Acids, 2006, s. 127–142. DOI: 10.1007/s00726-005-0247-0. PMID 16547652.
↑ C.A. Fulcher. Pathway: L-tryptophan biosynthesis . MetaCyc Metabolic Pathway Database, 2010-02-12. Dostupné online.
↑ Evolution of a Biosynthetic Pathway: The Tryptophan Paradigm. Annual Review of Microbiology, 1989, s. 567–600. DOI: 10.1146/annurev.mi.43.100189.003031. PMID 2679363.
↑ ELLIOTT, Katherine; FITZSIMONS, David W.. Purine and Pyrimidine Metabolism. : , 16 September 2009. ISBN 9780470717981. S. 143–158.
↑ Macrocytic anemia in Lesch–Nyhan disease and its variants. Genetics in Medicine, 2019, s. 353–360. DOI: 10.1038/s41436-018-0053-1. PMID 29875418.

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[IMP-1] R. Caspi. Pathway: 5-aminoimidazole ribonucleotide biosynthesis I . MetaCyc Metabolic Pathway Database, 2009-01-13. Dostupné online.

[Zhang2-2] Structural biology of the purine biosynthetic pathway. Cellular and Molecular Life Sciences, 2008, s. 3699–3724. DOI: 10.1007/s00018-008-8295-8.

[3] GUPTA, Rani; GUPTA, Namita. Fundamentals of Bacterial Physiology and Metabolism. : , 2021. ISBN 978-981-16-0722-6. DOI:10.1007/978-981-16-0723-3_19 Nucleotide Biosynthesis and Regulation, s. 525–554.

[Dance-4] A "Radical Dance" in Thiamin Biosynthesis: Mechanistic Analysis of the Bacterial Hydroxymethylpyrimidine Phosphate Synthase. Angewandte Chemie International Edition, 2010, s. 8653–8656. DOI: 10.1002/anie.201003419. PMID 20886485.

[HBI-5] R. Caspi. Pathway: 5-hydroxybenzimidazole biosynthesis (anaerobic) . MetaCyc Metabolic Pathway Database, 2019-09-23. Dostupné online.

[6] MEHTA, Angad P.; ABDELWAHED, Sameh H.; FENWICK, Michael K.. Anaerobic 5-Hydroxybenzimidazole Formation from Aminoimidazole Ribotide: An Unanticipated Intersection of Thiamin and Vitamin B12 Biosynthesis. Journal of the American Chemical Society, 2015-08-26, roč. 137, čís. 33, s. 10444–10447. Dostupné online . ISSN 0002-7863. DOI: 10.1021/jacs.5b03576.

[7] Crystal structure of human phosphoribosylpyrophosphate synthetase 1 reveals a novel allosteric site. Biochemical Journal, January 2007, s. 39–47. DOI: 10.1042/BJ20061066. PMID 16939420.

[8] R. Caspi. 5-phospho-α-D-ribose 1-diphosphate . MetaCyc Metabolic Pathway Database, 2022-02-15. Dostupné online.

[9] Structural Complexes of Human Adenine Phosphoribosyltransferase Reveal Novel Features of the APRT Catalytic Mechanism. Journal of Biomolecular Structure and Dynamics, 2008, s. 589–597. DOI: 10.1080/07391102.2008.10507205. PMID 18399692.

[pmid121759032-10] Mutational spectral analysis at the HPRT locus in healthy children. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 2002, s. 27–41. DOI: 10.1016/S0027-5107(02)00119-7. PMID 12175903.

[11] A new paradigm for biochemical energy coupling. Salmonella typhimurium nicotinate phosphoribosyltransferase. Journal of Biological Chemistry, 1993, s. 26004–26010. DOI: 10.1016/S0021-9258(19)74485-8. PMID 7503993.

[González-Segura-12] Ternary Complex Formation and Induced Asymmetry in Orotate Phosphoribosyltransferase. Biochemistry, 2007, s. 14075–14086. DOI: 10.1021/bi701023z. PMID 18020427.

[pmid22182754-13] Dynamic dissociating homo-oligomers and the control of protein function. Archives of Biochemistry and Biophysics, 2012, s. 131–143. DOI: 10.1016/j.abb.2011.11.020. PMID 22182754.

[14] Guanine and Xanthine Phosphoribosyltransfer Activities of Lactobacillus casei and Escherichia coli. Journal of Biological Chemistry, 1970, s. 2605–2611. DOI: 10.1016/S0021-9258(18)63113-8.

[:0-15] VOET, Donald. Fundamentals of biochemistry : life at the molecular level. Hoboken, NJ : , 2016. (Fifth edition.) Dostupné online. ISBN 978-1-118-91840-1.

[16] R. Caspi. Pathway: L-histidine biosynthesis . MetaCyc Metabolic Pathway Database, 2008-10-10. Dostupné online.

[17] Histidine biosynthesis in plants. Amino Acids, 2006, s. 127–142. DOI: 10.1007/s00726-005-0247-0. PMID 16547652.

[18] C.A. Fulcher. Pathway: L-tryptophan biosynthesis . MetaCyc Metabolic Pathway Database, 2010-02-12. Dostupné online.

[19] Evolution of a Biosynthetic Pathway: The Tryptophan Paradigm. Annual Review of Microbiology, 1989, s. 567–600. DOI: 10.1146/annurev.mi.43.100189.003031. PMID 2679363.

[20] ELLIOTT, Katherine; FITZSIMONS, David W.. Purine and Pyrimidine Metabolism. : , 16 September 2009. ISBN 9780470717981. S. 143–158.

[21] Macrocytic anemia in Lesch–Nyhan disease and its variants. Genetics in Medicine, 2019, s. 353–360. DOI: 10.1038/s41436-018-0053-1. PMID 29875418.

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