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Gene Review

PTS  -  6-pyruvoyltetrahydropterin synthase

Homo sapiens

Synonyms: 6-pyruvoyl tetrahydrobiopterin synthase, PTP synthase, PTPS
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Disease relevance of PTS


Psychiatry related information on PTS

  • BH4 deficiency results in hyperphenylalaninemia and monoamine neurotransmitter depletion associated with progressive mental retardation and is most commonly due to autosomal recessive mutations in 6-pyruvoyltetrahydropterin synthase (PTPS), the second enzyme for cofactor biosynthesis [6].
  • L. plantarum is a species that is encountered in many different environmental niches, and this flexible and adaptive behavior is reflected by the relatively large number of regulatory and transport functions, including 25 complete PTS sugar transport systems [7].
  • The subjects were assessed by psychotherapeutic interview, Offer Self-Image Questionnaire (OSIQ), questionnaires of depressive symptoms, war stressors, posttraumatic reactions (PTS-reactions) and general data [8].

High impact information on PTS

  • The disparate subcellular locations of PTS receptor homologs have led to proposals of receptor shuttling between the cytosol and the peroxisomal membrane, and to the suggestion that some of these molecules may even reside normally in the peroxisomal matrix [9].
  • To carry out its catalytic function in sugar transport and phosphorylation, the PTS uses PEP as an energy source and phosphoryl donor [10].
  • The organization of the PTS as a four-step phosphoryl transfer system, in which all P derivatives exhibit similar energy (phosphorylation occurs at histidyl or cysteyl residues), is surprising, as a single protein (or domain) coupling energy transfer and sugar phosphorylation would be sufficient for PTS function [10].
  • As we shall see, the PTS regulation network not only controls carbohydrate uptake and metabolism but also interferes with the utilization of nitrogen and phosphorus and the virulence of certain pathogens [10].
  • We report analyses of 202 fully sequenced genomes for homologues of known protein constituents of the bacterial phosphoenolpyruvate-dependent phosphotransferase system (PTS) [11].

Chemical compound and disease context of PTS

  • All three mutations, R25Q, R16C, and K120-->Stop, affect evolutionarily conserved residues in PTPS, result in reduced enzymatic activity when reconstituted in E. coli, and are thus believed to be the molecular cause for the BH4 deficiency [2].
  • The new combined loading test was performed in nine patients with primary HPA, three with classical phenylketonuria (PKU), three with DHPR deficiency, and three with 6-pyruvoyl tetrahydropterin synthase (PTPS) deficiency [12].
  • The genes encoding the proteins of the fructose-specific phosphotransferase system (PTS) of Rhodobacter capsulatus were sequenced, and the deduced amino acyl sequences of the energy-coupling protein, Enzyme I, and the transport protein, Enzyme IIfru, were compared with published sequences [13].
  • While most strains of Streptococcus thermophilus do not or poorly metabolize glucose, compelling evidence suggests that S. thermophilus possesses the genes that encode the glucose/mannose general and specific PTS proteins [14].
  • Most strains of Escherichia coli K-12 are unable to use the enzyme IIA/IIB (enzyme IIMan) complex of the phosphoenolpyruvate:sugar phosphotransferase system (PTS) in anaerobic growth and therefore cannot utilize glucosamine anaerobically [15].

Biological context of PTS


Anatomical context of PTS


Associations of PTS with chemical compounds


Enzymatic interactions of PTS


Other interactions of PTS

  • PTS-P1 has 74% similarity to the 3' portion of PTPS cDNA [17].
  • Importantly, IL-1beta induced PTPS rather than GTPCH [20].
  • In order to investigate their putative function and biosynthetic regulation, we performed quantitative analysis of not only the intracellular pteridines by HPLC but also the biosynthetic enzymes (GTP cyclohydrolase I, 6-pyruvoyltetrahydropterin synthase, SR, and aldose reductase-like enzyme) by Northern blot analysis and activity assay [25].
  • This study indicates that genetic abnormality in the 6-PTS gene may be a hereditary dystonia disorder [21].
  • Using a more purified human liver sepiapterin reductase fraction which gave a lower yield than a crude preparation, adult controls (n = 8) showed a mean erythrocyte PTS activity of 17.6 (range 11.0-29.5) microU/g Hb [1].

Analytical, diagnostic and therapeutic context of PTS

  • On immunostimulation, PTPS became rate-limiting [20].
  • In this study, five additional mutations in the PTS gene, namely 200C>T (T67M), 226C>T (L76F), IVS3+1G>A (K54X), 116-119delTGTT (K38X) and 169-171delGTG (V57del), were identified by PCR and DNA sequencing in Chinese PTS-deficient patients [23].
  • Two single base alterations of PTPS cDNA, a C-to-T transition at nucleotide 259 and a novel A-to-G transition at nucleotide 155 (according to cDNA sequence), were identified in two Chinese PTPS-deficient siblings by the reverse transcription-polymerase chain reaction (RT-PCR) [26].
  • However, although thrombolytic therapy is advantageous over anticoagulation as measured by early vein patency, a benefit in terms of a reduction in PTS risk, is unproven [27].
  • The intra and interlaboratory reproducibilities of Recombiplastin, calculated on the basis of either PTS expressed in seconds, or of the International Normalized Ratio (INR), were good, with coefficients of variation (CV) similar to those observed with the 5 other reagents used by the different laboratories (2% < CV < 8%) [28].


  1. Tetrahydrobiopterin deficiency: assay for 6-pyruvoyl-tetrahydropterin synthase activity in erythrocytes, and detection of patients and heterozygous carriers. Shintaku, H., Niederwieser, A., Leimbacher, W., Curtius, H.C. Eur. J. Pediatr. (1988) [Pubmed]
  2. Hyperphenylalaninemia due to defects in tetrahydrobiopterin metabolism: molecular characterization of mutations in 6-pyruvoyl-tetrahydropterin synthase. Thöny, B., Leimbacher, W., Blau, N., Harvie, A., Heizmann, C.W. Am. J. Hum. Genet. (1994) [Pubmed]
  3. Identification of mutations causing 6-pyruvoyl-tetrahydropterin synthase deficiency in four Italian families. Oppliger, T., Thöny, B., Kluge, C., Matasovic, A., Heizmann, C.W., Ponzone, A., Spada, M., Blau, N. Hum. Mutat. (1997) [Pubmed]
  4. Structure and function of proteins involved in sugar transport by the PTS of gram-positive bacteria. Hengstenberg, W., Reiche, B., Eisermann, R., Fischer, R., Kessler, U., Tarrach, A., De Vos, W.M., Kalbitzer, H.R., Glaser, S. FEMS Microbiol. Rev. (1989) [Pubmed]
  5. The phosphoenolpyruvate:sugar phosphotransferase system of oral streptococci and its role in the control of sugar metabolism. Vadeboncoeur, C., Pelletier, M. FEMS Microbiol. Rev. (1997) [Pubmed]
  6. Retrovirus-mediated double transduction of the GTPCH and PTPS genes allows 6-pyruvoyltetrahydropterin synthase-deficient human fibroblasts to synthesize and release tetrahydrobiopterin. Laufs, S., Blau, N., Thöny, B. J. Neurochem. (1998) [Pubmed]
  7. Complete genome sequence of Lactobacillus plantarum WCFS1. Kleerebezem, M., Boekhorst, J., van Kranenburg, R., Molenaar, D., Kuipers, O.P., Leer, R., Tarchini, R., Peters, S.A., Sandbrink, H.M., Fiers, M.W., Stiekema, W., Lankhorst, R.M., Bron, P.A., Hoffer, S.M., Groot, M.N., Kerkhoven, R., de Vries, M., Ursing, B., de Vos, W.M., Siezen, R.J. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  8. Self-image and refugee status in adolescents from Bosnia and Herzegovina and Croatia. Begovac, I., Begovac, B., Rudan, V. Collegium antropologicum. (2003) [Pubmed]
  9. Convergence of model systems for peroxisome biogenesis. Subramani, S. Curr. Opin. Cell Biol. (1996) [Pubmed]
  10. How phosphotransferase system-related protein phosphorylation regulates carbohydrate metabolism in bacteria. Deutscher, J., Francke, C., Postma, P.W. Microbiol. Mol. Biol. Rev. (2006) [Pubmed]
  11. Comparative genomic analyses of the bacterial phosphotransferase system. Barabote, R.D., Saier, M.H. Microbiol. Mol. Biol. Rev. (2005) [Pubmed]
  12. Differential diagnosis of hyperphenylalaninaemia by a combined phenylalanine-tetrahydrobiopterin loading test. Ponzone, A., Guardamagna, O., Spada, M., Ferraris, S., Ponzone, R., Kierat, L., Blau, N. Eur. J. Pediatr. (1993) [Pubmed]
  13. On the evolutionary origins of the bacterial phosphoenolpyruvate:sugar phosphotransferase system. Wu, L.F., Saier, M.H. Mol. Microbiol. (1990) [Pubmed]
  14. Genetic and biochemical characterization of the phosphoenolpyruvate:glucose/mannose phosphotransferase system of Streptococcus thermophilus. Cochu, A., Vadeboncoeur, C., Moineau, S., Frenette, M. Appl. Environ. Microbiol. (2003) [Pubmed]
  15. Genetic locus, distant from ptsM, affecting enzyme IIA/IIB function in Escherichia coli K-12. Roehl, R.A., Vinopal, R.T. J. Bacteriol. (1980) [Pubmed]
  16. Chromosomal location of two human genes encoding tetrahydrobiopterin-metabolizing enzymes: 6-pyruvoyl-tetrahydropterin synthase maps to 11q22.3-q23.3, and pterin-4 alpha-carbinolamine dehydratase maps to 10q22. Thöny, B., Heizmann, C.W., Mattei, M.G. Genomics (1994) [Pubmed]
  17. Chromosomal localization, genomic structure and characterization of the human gene and a retropseudogene for 6-pyruvoyltetrahydropterin synthase. Kluge, C., Brecevic, L., Heizmann, C.W., Blau, N., Thöny, B. Eur. J. Biochem. (1996) [Pubmed]
  18. Hyperphenylalaninemia due to deficiency of 6-pyruvoyl tetrahydropterin synthase. Unusual gene dosage effect in heterozygotes. Scriver, C.R., Clow, C.L., Kaplan, P., Niederwieser, A. Hum. Genet. (1987) [Pubmed]
  19. Diagnosis of dopa-responsive dystonia and other tetrahydrobiopterin disorders by the study of biopterin metabolism in fibroblasts. Bonafé, L., Thöny, B., Leimbacher, W., Kierat, L., Blau, N. Clin. Chem. (2001) [Pubmed]
  20. Critical role of interleukin-1beta for transcriptional regulation of endothelial 6-pyruvoyltetrahydropterin synthase. Franscini, N., Blau, N., Walter, R.B., Schaffner, A., Schoedon, G. Arterioscler. Thromb. Vasc. Biol. (2003) [Pubmed]
  21. 6-Pyruvoyl-tetrahydropterin synthase deficiency with generalized dystonia and diurnal fluctuation of symptoms: a clinical and molecular study. Hanihara, T., Inoue, K., Kawanishi, C., Sugiyama, N., Miyakawa, T., Onishi, H., Yamada, Y., Osaka, H., Kosaka, K., Iwabuchi, K., Owada, M. Mov. Disord. (1997) [Pubmed]
  22. Regulation of 6-pyruvoyltetrahydropterin synthase activity and messenger RNA abundance in human vascular endothelial cells. Linscheid, P., Schaffner, A., Blau, N., Schoedon, G. Circulation (1998) [Pubmed]
  23. Identification of three novel 6-pyruvoyl-tetrahydropterin synthase gene mutations (226C>T, IVS3+1G>A, 116-119delTGTT) in Chinese hyperphenylalaninemia caused by tetrahydrobiopterin synthesis deficiency. Liu, T.T., Chang, Y.H., Chiang, S.H., Yang, Y.L., Yu, W.M., Hsiao, K.J. Hum. Mutat. (2001) [Pubmed]
  24. Bioinformatic analyses of bacterial HPr kinase/phosphorylase homologues. Stonestrom, A., Barabote, R.D., Gonzalez, C.F., Saier, M.H. Res. Microbiol. (2005) [Pubmed]
  25. Functional role of sepiapterin reductase in the biosynthesis of tetrahydropteridines in Dictyostelium discoideum Ax2. Choi, Y.K., Kong, J.S., Park, Y.S. Biochim. Biophys. Acta (2006) [Pubmed]
  26. Identification of a common 6-pyruvoyl-tetrahydropterin synthase mutation at codon 87 in Chinese phenylketonuria caused by tetrahydrobiopterin synthesis deficiency. Liu, T.T., Hsiao, K.J. Hum. Genet. (1996) [Pubmed]
  27. Thrombolysis in deep vein thrombosis: is there still an indication? Wells, P.S., Forster, A.J. Thromb. Haemost. (2001) [Pubmed]
  28. French multicentric evaluation of recombinant tissue factor (recombiplastin) for determination of prothrombin time. Roussi, J., Drouet, L., Samama, M., Sié, P. Thromb. Haemost. (1994) [Pubmed]
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