The tetrahydrobiopterin pathway and pain

Current Opinion in Investigational Drugs

Volumn 11, Issue 1, 2010, Pages 19-30

  Naylor, Alasdair M ^a   Pojasek, Kevin R ^b   Hopkins, Andrew L ^c   Blagg, Julian ^d  

^a 6 Denne Hill Business Centre   (United Kingdom)

^b 4 Cambridge Center   (United States)

^c UNIVERSITY OF DUNDEE   (United Kingdom)

^d IMPERIAL CANCER RESEARCH FUND   (United Kingdom)

Author keywords

Chronic pain; GCH1 pain protective haplotype; Guanosine triphosphate cyclohydrolase 1 (GCH1); Neuropathic pain; Sepiapterin reductase (SPR); Tetrahydrobiopterin (BH4)

Indexed keywords

1 (8 HYDROXY 3,4 DIHYDRO 1H ISOQUINOLIN 2 YL)ETHANONE; 2,4 DIAMINO 6 HYDROXYPYRIMIDINE; 5,6,7,8 TETRAHYDRO DEXTRO NEOPTERIN; 5,6,7,8 TETRAHYDRO LEVO BIOPTERIN; 6 PYRUVOYLTETRAHYDROPTERIN SYNTHASE; 7,8 DIHYDRO DEXTRO NEOPTERIN; 7,8 DIHYDRO LEVO BIOPTERIN; 8 AZAGUANINE; 8 CARBOETHOXY 7 DEAZAGUANINE; 8 MERCAPTOGUANINE; 8 METHYL 7 DEAZAGUANINE; DEXTROLEVO 6 METHYL 5,6,7,8 TETRAHYDROPTERIN; GUANOSINE TRIPHOSPHATE CYCLOHYDROLASE I; LEVO SEPIAPTERIN; N ACETYLDOPAMINE; N ACETYLSEROTONIN; N CHLOROACETYLDOPAMINE; N CHLOROACETYLSEROTONIN; N METHOXYACETYLSEROTONIN; OXIDOREDUCTASE INHIBITOR; PYRIMIDINE DERIVATIVE; SEPIAPTERIN REDUCTASE; TETRAHYDROBIOPTERIN; THIOGUANINE DERIVATIVE; UNCLASSIFIED DRUG;

CHRONIC PAIN; COMPETITIVE INHIBITION; DRUG MECHANISM; DRUG STRUCTURE; DRUG TARGETING; ENZYME ACTIVE SITE; ENZYME STRUCTURE; HAPLOTYPE; HUMAN; MOLECULAR DYNAMICS; NEUROCHEMISTRY; NEUROPATHIC PAIN; NONHUMAN; PAIN; PHARMACOPHORE; POSTOPERATIVE PAIN; PROTEIN SYNTHESIS; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; STRUCTURE ACTIVITY RELATION;

ALCOHOL OXIDOREDUCTASES; ANIMALS; BIOPTERIN; DRUG DISCOVERY; GTP CYCLOHYDROLASE; HUMANS; PAIN; PERIPHERAL NERVOUS SYSTEM DISEASES; SIGNAL TRANSDUCTION;

EID: 74549212539     PISSN: 14724472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (57)

1. Gore M, Dukes E, Rowbotham DJ, Tai KS, Leslie D: Clinical characteristics and pain management among patients with painful peripheral neuropathic disorders in general practice settings. Eur J Pain (2007) 11(6):652-664.
2. Costigan M, Scholz J, Woolf CJ: Neuropathic pain - A maladaptive response of the nervous system to damage. Ann Rev Neurosci (2009) 32:1-32.
3. Woolf CJ, Mannion RJ: Neuropathic pain: Aetiology, symptoms, mechanisms, and management. Lancet (1999) 353(9168):1959-1964.
4. Dworkin RH, Backonja M, Rowbotham MC, Allen RR, Argoff CR, Bennett GJ, Bushnell MC, Farrar JT, Galer BS, Haythornthwaite JA, Hewitt DJ et al: Advances in neuropathic pain: Diagnosis, mechanisms, and treatment recommendations. Arch Neurol (2003) 60(11):1524-1534.
5. Dieleman JP, Kerklaan J, Huygen FJ, Bouma PA, Sturkenboom MC: Incidence rates and treatment of neuropathic pain conditions in the general population. Pain (2008) 137(3):681-688.
6. Costigan M, Befort K, Karchewski L, Griffin RS, D'Urso D, Allchorne A, Sitarski J, Mannion JW, Pratt RE, Woolf CJ: Replicate high density rat genome oligonucleotide microarrays reveal hundreds of regulated genes in the dorsal root ganglion after peripheral nerve injury. BMC Neurosci (2002) 3:16.
7. Tegeder I, Costigan M, Griffin RS, Abele A, Belfer I, Schmidt H, Ehnert C, Nejim J, Marian C, Scholz J, Wu T et al: GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence. Nat Med (2006) 12(11):1269-1277.
8. Thöny B, Auerbach G, Blau N: Tetrahydrobiopterin biosynthesis, regeneration and functions. Biochem J (2000) 347(Pt 1):1-16.
9. Gesierich A, Niroomand, Tiefenbacher CP: Role of human GTP cyclohydrolase I and its regulatory protein in tetrahydrobiopterin metabolism. Basic Res Cardiol (2003) 98(2):69-75.
10. Harada T, Kagamiyama H, Hatakeyama K: Feedback regulation mechanisms for the control of GTP cyclohydrolase I activity. Science (1993) 260(5113):1507-1510.
11. Maita N, Okada K, Hatakeyama K, Hakoshima T: Crystal structure of the stimulatory complex of GTP cyclohydrolase I and its feedback regulatory protein GFRP. Proc Natl Acad Sci USA (2002) 99(3):1212-1217.
12. Gross SS, Levi R: Tetrahydrobiopterin synthesis: An absolute requirement for cytokine-induced nitric oxide generation by vascular smooth muscle. J Biol Chem (1992) 267(36):25722-25729.
13. Rosenkranz-Weiss P, Sessa WC, Milstien S, Kaufman S, Watson CA, Pober JS: Regulation of nitric oxide synthesis by proinflammatory cytokines in human umbilical vein endothelial cells. Elevations in tetrahydrobiopterin levels enhance endothelial nitric oxide synthase specific activity. J Clin Invest (1994) 93(5):2236-2243.
14. Dobbie M, Crawley J, Waruiru C, Marsh K, Surtees R: Cerebrospinal fluid studies in children with cerebral malaria: An excitotoxic mechanism? Am J Trop Med Hyg (2000) 62(2):284-290.
15. Hoshiai K, Hattan N, Fukuyama N, Tadaki F, Hida M, Saito A, Nakanishi N, Hattori Y, Nakazawa H: Increased plasma tetrahydrobiopterin in septic shock is a possible therapeutic target. Pathophysiology (2001) 7(4):275-281.
16. Chiarini A, Armato U, Pacchiana R, Dal Pra I: Proteomic analysis of GTP cyclohydrolase 1 multiprotein complexes in cultured normal adult human astrocytes under both basal and cytokineactivated conditions. Proteomics (2009) 9(7):1850-1860.
17. Ichinose H, Ohye T, Takahashi E, Seki N, Hori T, Segawa M, Nomura Y, Endo K, Tanaka H, Tsuji S, Jujita K et al: Hereditary progressive dystonia with marked diurnal fluctuation caused by mutations in the GTP cyclohydrolase I gene. Nat Genet (1994) 8(3):236-242.
18. Bonafé L, Thöny B, Penzien JM, Czarnecki B, Blau N: Mutations in the sepiapterin reductase gene cause a novel tetrahydrobiopterin-dependent monoamine neurotransmitter deficiency without hyperphenylalanine emia. Am J Hum Genet (2001) 69(2):269-277.
19. Antoniades C, Shirodaria C, Van Assche T, Cunnington C, Tegeder I, Lötsch J, Guzik TJ, Leeson P, Diesch J, Tousoulis D, Stefanadis C et al: GCH1 haplotype determines vascular and plasma biopterin availability in coronary artery disease. J Am Coll Cardiol (2008) 52(2):158-165.
20. Max MB, Stewart WF: The molecular epidemiology of pain: A new discipline for drug discovery. Nat Rev Drug Discov (2008) 7(8):647-658.
21. Tegeder I, Adolph J, Schmidt H, Woolf CJ, Geisslinger G, Lötsch J: Reduced hyperalgesia in homozygous carriers of a GTP cyclohydrolase I haplotype. Eur J Pain (2008) 12(8):1069-1077.
22. Lötsch J, Belfer I, Kirchhof A, Mishra BK, Max MB, Doehring A, Costigan M, Woolf CJ, Geisslinger G, Tegeder I: Reliable screening for a pain-protective haplotype in the GTP cyclohydrolase I gene (GCH1) through the use if 3 or fewer single nucleotide polymorphisms. Clin Chem (2007) 53(6):1010-1015.
23. Diatchenko L, Slade GD, Nackley AG, Bhalang K, Sigurdsson A, Belfer I, Goldman D, Xu K, Shabalina SA, Shagin D, Max MB et al: Genetic basis for individual variations in pain perception and the development of a chronic pain condition. Hum Mol Genet (2005) 14(1):135-143.
24. Goldberg YP, MacFarlane J, MacDonald ML, Thompson J, Dube MP, Mattice M, Fraser R, Young C, Hossain S, Pape T, Payne B et al: Loss-of-function mutations in the Nav1.7 gene underlie congenital indifferences to pain in multiple human populations. Clin Genet (2007) 71(4):311-319.
25. Diatchenko L, Nackley AG, Tchinvileva IE, Shabaline SA, Maixner W: Genetic architecture of human pain perception. Trends Genet (2007) 23(12):605-613.
26. Norbury TA, MacGregor AJ, Urwin J, Spector TD, McMahon SB: Heritability of responses to painful stimuli in women: A classical twin study. Brain (2007) 130(Pt 11):3041-3049.
27. Nielsen CS, Stubhaug A, Price DD, Vassend O, Czajkowski N, Harris JR: Individual differences in pain sensitivity: Genetic and environmental contributions. Pain (2008) 136(1-2):21-29.
28. Campbell CM, Edwards RR, Carmona C, Uhart M, Wand G, Carteret A, Kim YK, Frost J, Campbell JN: Polymorphisms in the GTP cyclohydrolase gene (GCH1) are associated with ratings of capsaicin pain. Pain (2009) 141(1-2):114-118.
29. Kim H, Dionne RA: Lack of influence of GTP cyclohydrolase gene (GCH1) variations on pain sensitivity in humans. Mol Pain (2007) 3:6.
30. Edwards RR, Sarlani E, Wesselmann U, Fillingim RB: Quantitative assessment of experimental pain perception: Multiple domains of clinical relevance. Pain (2005) 114(3):315-319.
31. Nar H, Huber R, Meining W, Schmid C, Weinkauf S, Bacher A: Atomic structure of GTP cyclohydrolase I. Structure (1995) 3(5):459-466.
32. Auerbach G, Herrmann A, Bracher A, Bader G, Gutlich M, Fischer M, Neukamm M, Garrido-Franco M, Richardson J, Nar H, Huber R et al: Zinc plays a key role in human and bacterial GTP cyclohydrolase I. Proc Natl Acad Sci USA (2000) 97(25):13567-13572.
33. Rebelo J, Auerbach G, Bader G, Brocher A, Nar H, Hösl C, Schramek N, Kaiser J, Bacher A, Huber R, Fischer M: Biosynthesis of pteridines. Reaction mechanism of GTP cyclohydrolase I. J Mol Biol (2003) 326(2):503-516.
34. Betts L, Xiang S, Short SA, Wolfenden R, Carter CW: Cytidine deaminase. The 2.3Å cyrystal structure of an enzyme: Transition state analog complex. J Mol Biol (1994) 235(2): 635-656.
35. Bracher A, Eisenreich W, Schramek N, Ritz H, Götze E, Herrmann A, Gütlich M, Bacher A: Biosynthesis of pteridines: NMR studies on the reaction mechanisms of GTP cyclohydrolase I, pyruvoyltetrahydropterin synthase, and sepiapterin reductase. J Biol Chem (1998) 273(43):28132-28141.
36. Tanaka K, Nakagawa N, Kuramitsu S, Yokoyama S, Masui R: Novel reaction mechanism of GTP cyclohydrolase I. High resolution X-ray crystallography of Thermus thermophilus HB8 enzyme complexed with transition state analogue, the 8-oxoguanine derivative. J Biochem (2005) 138(3):263-275.
37. Yoneyama, T, Wilson LM, Hatakeyama K: GTP cyclohydrolase I feedback regulatory protein-dependent and independent inhibition of GTP cyclohydrolase I. Arch Biochem Biophys (2001) 388(1):67-73.
38. Gibson CL, Paulini K, Suckling CJ: Synthesis of potential inhibitors of GTP-cyclohydrolase I: An efficient synthesis of 8-substituted 7-deazaguanines. Chem Commun (1997) (4):371-372.
39. Gibson CL, LaRosa S, Ohta K, Boyle PH, Leurquin F, LeMacon A, Suckling CJ: The synthesis of 7-deazaguanines as potential inhibitors of guanosine triphosphate cyclohydrolase I. Tetrahedron (2004) 60(4):943-959.
40. Harada T, Kagamiyama H, Hatakeyama K: Feedback regulation mechanisms for the control of GTP cyclohydrolase I activity. Science (1993) 260(5113):1507-1510.
41. Yoneyama T, Brewer JM, Hatekayama K: GTP cyclohydrolase I feedback regulatory protein is a pentamer of identical subunits. Purification, cDNA cloning and bacterial expression. J Biol Chem (1997) 272(15):9690-9696.
42. Xie L, Smith JA, Gross SS: GTP cyclohydrolase I inhibition by the prototypic inhibitor 2, 4-diamino-6-hydroxypyrimidine. Mechanisms and unanticipated role of GTP cyclohydrolase I feedback regulatory protein. J Biol Chem (1998) 273(33): 21091-21098.
43. Kolinsky M, Gross SS: The mechanism of potent GTP cyclohydrolase I inhibition by 2,4-diamino-6-hydroxypyrimidine: Requirement of the GTP cyclohydrolase I feedback regulatory protein. J Biol Chem (2004) 279(39):40677-40682.
44. Shen RS, Alam A, Zhang YX: Inhibition of GTP cyclohydrolase I by pterins. Biochim Biophys Acta (1988) 965(1):9-15.
45. Ploom T, Thöny B, Yim J, Lee S, Nar H, Leimbacher W, Richardson J, Huber R, Auerbach G: Crystallographic and kinetic investigations on the mechanism of 6-pyruvoyl tetrahydropterin synthase. J Mol Biol (1999) 286(3):851-860.
46. Katoh S, Sueoka T, Yamada S: Direct inhibition of brain sepiapterin reductase by a catecholamine and an indoleamine. Biochem Biophys Res Commun (1982) 105(1):75-81.
47. Smith GK, Duch DS, Edelstein MP, Bigham, EC: New inhibitors of sepiapterin reductase. Lack of an effect of intracellular tetrahydrobiopterin depletion upon in vitro proliferation of two human cell lines. J Biol Chem (1992) 267(8):5599-5607.
48. Auerbach G, Herrmann A, Gutlich M, Fischer M, Jacob U, Bacher A, Huber R: The 1.25 Å crystal structure of sepiapterin reductase reveals its binding mode to pterins and brain neurotransmitters. EMBO J (1997) 16(24):7219-7230.
49. Supangat S, Seo KH, Choi YK, Park YS, Son D, Han CD, Lee KH: Structure of Chlorobium tepidum sepiapterin reductase complex reveals the novel substrate binding mode for stereospecific production of l-threo-tetrahydrobiopterin. J Biol Chem (2006) 281(4):2249-2256.
50. Crystal structure of human sepiapterin reductase in complex with NADP+: Research Collaboratory for Structural Bioinformatics Protein Data Bank (2009). www.rcsb.org/pdb/explore/explore.do? structureId=1Z6Z
51. Xie L, Smith JA, Gross SS: GTP cyclohydrolase I inhibition by the prototypic inhibitor 2, 4-diamino-6-hydroxypyrimidine. Mechanisms and unanticipated role of GTP cyclohydrolase I feedback regulatory protein. J Biol Chem (1998) 273(33):21091-21098.
52. Hamadate H, Noguchi K, Sakanashi M, Matsuzaki T, Nakasone J, Sakanashi M: Effect of decreased levels of intrinsic tetrahydropbiopterin on endothelial function in anesthetized rats. J Pharmacol Sci (2008) 107(1):49-56.
53. Mitchell BM, Dorrance AM, Webb RC: GTP cyclohydrolase I inhibition attenuates vasodilation and increases blood pressure in rats. (2003) Am J Physiol 285(5):H2165-H2170.
54. Harrison D, Griendling KK, Landmesser U, Hornig B, Drexler H: Role of oxidative stress in atherosclerosis. Am J Cardiol (2003) 91(3A):7A-11A.
55. Zhang L, Rao F, Zhang K, Khandrika S, Das M, Vaingankar SM, Bao X, Rana BK, Smith DW, Wessel J, Salem RM et al: Discovery of common human genetic variants of GTP cyclohydrolase I (GCH1) governing nitric oxide, autoimmune activity, and cardiovascular risk. J Clin Invest (2007) 117(9):2658-2671.
56. Doehring A, Antoniades C, Channon KM, Tegeder I, Lötsch J: Clinical genetics of functionally mild non-codong GTP cyclohydrolase I (GCH1) polymorphisms modulating pain and cardiovascular risk. (2008) Mutat Res 659(3):195-201.
57. Lazarev M, Lamb J, Barmada MM, Dai F, Anderson MA, Max MB, Whitcomb DC: Does the pain-protective GTP cyclohydrolase haplotype significantly alter the pattern or severity of pain in humans with chronic pancreatitis? Mol Pain (2008) 4:58.