Tetrapyrroles pp 250-262 | Cite as

Regulation of Tetrapyrrole Synthesis in Higher Plants

  • Matthew J. Terry
  • Alison G. Smith
Part of the Molecular Biology Intelligence Unit book series (MBIU)


Regulation of the tetrapyrrole pathway in plants is particularly crucial, since it is required for efficient synthesis of the photosynthetic apparatus, protection from the harmful phototoxicity of the pathway intermediates, and because of the proposed role played by some of the intermediates in signaling. The four major products, chlorophyll, haem, sirohaem and phytochromobilin, all need to be assembled with their respective apoproteins and the production of both components needs to be carefully coordinated. This is especially true as many tetrapyrroles such as the chlorophylls and their precursors are extremely phototoxic as free compounds. The major control points of the pathway are: the formation of the initial precursor, 5-aminolaevulinic acid; and the metal-ion insertion steps at the branchpoint between haem and Mg-protoporphyrin, and the formation of sirohaem. Because of the necessary complexity of tetrapyrrole regulation a wide range of regulatory mechanisms are employed, including transcriptional regulation of key genes in response to both environmental and internal cues, and internal pathway regulation by dedicated regulatory proteins and pathway intermediates. Moreover, genetic and microarray evidence indicates a link between the flux through the pathway and expression of genes encoding chlorophyll apoproteins. Here we discuss our current understanding of how these mechanisms are coordinated to control flux through the pathway to meet the requirements of the cell under different conditions.


Nuclear Gene Expression Tetrapyrrole Biosynthesis Plastid Signal Uroporphyrinogen Decarboxylase HEMA Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Beale SI. Enzymes of chlorophyll biosynthesis. Photosynth Res 1999; 60:43–73.CrossRefGoogle Scholar
  2. 2.
    Papenbrock J, Grimm B. Regulatory network of tetrapyrrole biosynthesis—Studies of intracellular signalling involved in metabolic and developmental control of plastids. Planta 2001; 213:667–681.CrossRefPubMedGoogle Scholar
  3. 3.
    Cornah JE, Terry MJ, Smith AG. Green or red: What stops the traffic in the tetrapyrrole pathway? Trends Plant Sci 2003; 8:224–230.CrossRefPubMedGoogle Scholar
  4. 4.
    Smith AG, Cornah JE, Roper JM et al. Compartmentation of tetrapyrrole metabolism in higher plants. In: Bryant JA, Burrell MM, Kruger NJ, eds. Plant Carbohydrate Metabolism. Oxford: BIOS Scientific Publishers, 1999:281–294.Google Scholar
  5. 5.
    Papenbrock J, Pfundel E, Mock HP et al. Decreased and increased expression of the subunit CHL I diminishes Mg chelatase activity and reduces chlorophyll synthesis in transgenic tobacco plants. Plant J 2000; 22:155–164.CrossRefPubMedGoogle Scholar
  6. 6.
    Papenbrock J, Mock HP, Tanaka R et al. Role of magnesium chelatase activity in the early steps of the tetrapyrrole biosynthetic pathway. Plant Physiol 2000; 122:1161–1169.CrossRefPubMedGoogle Scholar
  7. 7.
    Castelfranco PA, Jones OTG. Protoheme turnover and chlorophyll synthesis in greening barley tissue. Plant Physiol 1975; 55:485–490.CrossRefPubMedGoogle Scholar
  8. 8.
    Santana MA, Pihakaski-Maunsbach K, Sandal N et al. Evidence that the plant host synthesizes the heme moiety of leghemoglobin in root nodules. Plant Physiol 1998; 116:1259–1269.CrossRefPubMedGoogle Scholar
  9. 9.
    Hamazato F, Shinomura T, Hanzawa H et al. Fluence and wavelength requirements for Arabidopsis CAB gene induction by different phytochromes. Plant Physiol 1997; 115:1533–1540.CrossRefPubMedGoogle Scholar
  10. 10.
    McCormac AC, Terry MJ. Light-signalling pathways leading to the coordinated expression of HEMA1 and Lhcb during chloroplast development in Arabidopsis thaliana. Plant J 2002; 32:549–559.CrossRefPubMedGoogle Scholar
  11. 11.
    Murray DL, Kohorn BD. Chloroplasts of Arabidopsis thaliana homozygous for the ch-1 locus lack chlorophyll b, lack stable LHCPII and have stacked thylakoids. Plant Mol Biol 1991; 16:71–79.CrossRefPubMedGoogle Scholar
  12. 12.
    Mochizuki N, Brusslan JA, Larkin R et al. Arabidopsis genomes uncoupled 5 (GUN5) mutant reveals the involvement of Mg-chelatase H subunit in plastid-to-nucleus signal transduction. Proc Natl Acad Sci USA 2001; 98:2053–2058.CrossRefPubMedGoogle Scholar
  13. 13.
    La Rocca N, Rascio N, Oster U et al. Amitrole treatment of etiolated barley seedlings leads to deregulation of tetrapyrrole synthesis and to reduced expression of Lhc and RbcS genes. Planta 2001; 213:101–108.CrossRefGoogle Scholar
  14. 14.
    Strand A, Asami T, Alonso J et al. Chloroplast to nucleus communication triggered by accumulation of Mg-protoporphyrin IX. Nature 2003; 421:79–83.CrossRefPubMedGoogle Scholar
  15. 15.
    Larkin RM, Alonso JM, Ecker JR et al. GUN4, a regulator of chlorophyll synthesis and intracellular signaling. Science 2003; 299:902–906.CrossRefPubMedGoogle Scholar
  16. 16.
    McCormac AC, Terry MJ. Loss of nuclear gene expression during the phytochrome A-mediated far-red block of greening response. Plant Physiol 2002; 130:402–414.CrossRefPubMedGoogle Scholar
  17. 17.
    Oster U, HB, Rüdiger W. The greening process in cress seedlings. V. Possible interference of chlorophyll precursors accumulated after thujaplicin treatment with light-regulated expression of Lhc genes. J Photochem Photobiol 1996; 36:255–261.CrossRefGoogle Scholar
  18. 18.
    Kropat J, Oster U, Rudiger W et al. Chlorophyll precursors are signals of chloroplast origin involved in light induction of nuclear heat-shock genes. Proc Natl Acad Sci USA 1997; 94:14168–14172.CrossRefPubMedGoogle Scholar
  19. 18a.
    Mochizuki N, Tanaka R, Tanaka A et al. The steady state level of Mg-protoporphyrin IX is not a determinant of plastid-to-nucleus signaling in Arabidopsis. Proc Natl Acad Sci USA, 2008; in press.Google Scholar
  20. 18b.
    Moulin M, McCormac AC, Terry MJ, Smith AC Tetrapyrrole profiling in Arabidopsis seedlings reveals that retrograde plastid nuclear signalling is not due to Mg-protoporphyrin IX accumulation. Proc Natl Acad Sci USA 2008; in press.Google Scholar
  21. 19.
    Beale SI, Weinstein JD. Biochemistry and regulation of photosynthetic pigment formation in plants and algae. In: Jordan PM, ed. Biosynthesis of Tetrapyrroles. Amsterdam: Elsevier, 1991:155–235.CrossRefGoogle Scholar
  22. 20.
    Gough SP, Westergren T, Hansson M. Chlorophyll biosynthesis in higher plants. Regulatory aspects of 5-aminolevulinate formation. J Plant Biol 2003; 46:135–160.CrossRefGoogle Scholar
  23. 21.
    Castelfranco PA, Zeng XH. Regulation of 5-aminolevulinic acid synthesis in developing chloroplasts.4. An endogenous inhibitor from the thylakoid membranes. Plant Physiol 1991; 97:1–6.CrossRefPubMedGoogle Scholar
  24. 22.
    Weinstein JD, Beale SI. Enzymatic conversion of glutamate to delta-aminolevulinate in soluble extracts of the unicellular green-alga, Chlorella-vulgaris. Arch Biochem Biophys 1985; 237:454–464.CrossRefPubMedGoogle Scholar
  25. 23.
    Thomas J, Weinstein JD. Free heme in isolated chloroplasts—An improved method of assay and its physiological importance. Plant Physiol Biochem 1992; 30:285–292.Google Scholar
  26. 24.
    Terry MJ, Kendrick RE. Feedback inhibition of chlorophyll synthesis in the phytochrome chromophore-deficient aurea and yellow-green-2 mutants of tomato. Plant Physiol 1999; 119:143–152.CrossRefPubMedGoogle Scholar
  27. 25.
    Ryberg M, Terry MJ. Analysis of protochlorophyllide reaccumulation in the phytochrome chromophore-deficient aurea and yg-2 mutants of tomato by in vivo fluorescence spectroscopy. Photosynth Res 2002; 74:195–203.CrossRefPubMedGoogle Scholar
  28. 26.
    Hu GS, Yalpani N, Briggs SP et al. A porphyrin pathway impairment is responsible for the phenotype of a dominant disease lesion mimic mutant of maize. Plant Cell 1998; 10:1095–1105.CrossRefPubMedGoogle Scholar
  29. 27.
    Ishikawa A, Okamoto H, Iwasaki Y et al. A deficiency of coproporphyrinogen III oxidase causes lesion formation in Arabidopsis. Plant J 2001; 27:89–99.CrossRefPubMedGoogle Scholar
  30. 28.
    Mock HP, Grimm B. Reduction of uroporphyrinogen decarboxylase by antisense RNA expression affects activities of other enzymes involved in tetrapyrrole biosynthesis and leads to light-dependent necrosis. Plant Physiol 1997; 113:1101–1112.PubMedGoogle Scholar
  31. 29.
    Kruse E, Mock HP, Grimm B. Reduction of coproporphyrinogen oxidase level by antisense RNA-synthesis leads to deregulated gene-expression of plastid proteins and affects the oxidative defense system. EMBO J 1995; 14:3712–3720.PubMedGoogle Scholar
  32. 30.
    Papenbrock J, Mishra S, Mock HP et al. Impaired expression of the plastidic ferrochelatase by antisense RNA synthesis leads to a necrotic phenotype of transformed tobacco plants. Plant J 2001; 28:41–50.CrossRefPubMedGoogle Scholar
  33. 31.
    Pontoppidan B, Kannangara CG. Purification and partial characterization of barley glutamyl-tRNA(Glu) reductase, the enzyme that directs glutamate to chlorophyll biosynthesis. Eur J Biochem 1994; 225:529–537.CrossRefPubMedGoogle Scholar
  34. 32.
    Vothknecht UC, Kannangara CG, von Wettstein D. Barley glutamyl tRNA(Glu) reductase: Mutations affecting haem inhibition and enzyme activity. Phytochem 1998; 47:513–519.CrossRefGoogle Scholar
  35. 33.
    McCormac AC, AF, Kumar AM et al. Regulation of HEMA1 expression by phytochrome and a plastid signal during de-etiolation in Arabidopsis thaliana. Plant J 2001; 25:549–561.CrossRefPubMedGoogle Scholar
  36. 34.
    Ujwal ML, McCormac AC, Goulding A et al. Divergent regulation of the HEMA gene family encoding glutamyl-tRNA reductase in Arabidopsis thaliana: Expression of HEMA2 is regulated by sugars, but is independent of light and plastid signalling. Plant Mol Biol 2002; 50:81–89.CrossRefGoogle Scholar
  37. 35.
    Huq E, Al-Sady B, Hudson M et al. Phytochrome-interacting factor 1 is a critical bHLH regulator of chlorophyll biosynthesis. Science 2004; 305:1937–1941.CrossRefPubMedGoogle Scholar
  38. 36.
    Kruse E, Grimm B, Beator J et al. Developmental and circadian control of the capacity for delta-aminolevulinic acid synthesis in green barley. Planta 1997; 202:235–241.CrossRefGoogle Scholar
  39. 37.
    Papenbrock J, Mock HP, Kruse E et al. Expression studies in tetrapyrrole biosynthesis: Inverse maxima of magnesium chelatase and ferrochelatase activity during cyclic photoperiods. Planta 1999; 208:264–273.CrossRefGoogle Scholar
  40. 38.
    Somers DE, Devlin PF, Kay SA. Phytochromes and cryptochromes in the entrainment of the Arabidopsis circadian clock. Science 1998; 282:1488–1490.CrossRefPubMedGoogle Scholar
  41. 39.
    Masuda T, Ohta H, Shioi Y et al. Stimulation of glutamyl-tRNA reductase activity by benzyladenine in greening cucumber cotyledons. Plant Cell Physiol 1995; 36:1237–1243.Google Scholar
  42. 40.
    Matsumoto F, Obayashi T, Sasaki-Sekimoto Y et al. Gene expression profiling of the tetrapyrrole metabolic pathway in Arabidopsis with a mini-array system. Plant Physiol 2004; 135:2379–2391.CrossRefPubMedGoogle Scholar
  43. 41.
    McCormac AC, Terry MJ. The nuclear genes Lhcb and HEMA1 are differentially sensitive to plastid signals and suggest distinct roles for the GUN1 and GUN5 plastid-signalling pathways during de-etiolation. Plant J 2004; 40:672–685.CrossRefPubMedGoogle Scholar
  44. 42.
    Meskauskiene R, Nater M, Goslings D et al. FLU: A negative regulator of chlorophyll biosynthesis in Arabidopsis thaliana. Proc Natl Acad Sci USA 2001; 98:12826–12831.CrossRefPubMedGoogle Scholar
  45. 43.
    Meskauskiene R, Apel K. Interaction of FLU, a negative regulator of tetrapyrrole biosynthesis, with the glutamyl-tRNA reductase requires the tetratricopeptide repeat domain of FLU. FEBS Lett 2002; 532:27–30.CrossRefPubMedGoogle Scholar
  46. 44.
    Goslings D, Meskauskiene R, Kim C et al. Concurrent interactions of heme and FLU with Glu tRNA reductase (HEMA1), the target of metabolic feedback inhibition of tetrapyrrole biosynthesis, in dark-and light-grown Arabidopsis plants. Plant J 2004 2004; 40:957–967.CrossRefPubMedGoogle Scholar
  47. 45.
    Suzuki T, Masuda T, Singh DP et al. Two types of ferrochelatase in photosynthetic and nonphotosynthetic tissues of cucumber—Their difference in phylogeny, gene expression, and localization. J Biol Chem 2002; 277:4731–4737.CrossRefPubMedGoogle Scholar
  48. 46.
    Singh DP, Cornah JE, Hadingham S et al. Expression analysis of the two ferrochelatase genes in Arabidopsis in different tissues and under stress conditions reveals their different roles in haem biosynthesis. Plant Mol Biol 2002; 50:773–788.CrossRefPubMedGoogle Scholar
  49. 47.
    Leustek T, Smith M, Murillo M et al. Siroheme biosynthesis in higher plants—Analysis of an S-adenosyl-L-methionine-dependent uroporphyrinogen III methyltransferase from Arabidopsis thaliana. J Biol Chem 1997; 272:2744–2752.CrossRefPubMedGoogle Scholar
  50. 48.
    Raux-Deery E, Leech HK, Nakrieko KA et al. Identification and characterization of the terminal enzyme of siroheme biosynthesis from Arabidopsis thaliana—A plastid-located sirohydrochlorin ferrochelatase containing a 2Fe-2S center. J Biol Chem 2005; 280:4713–4721.CrossRefPubMedGoogle Scholar
  51. 49.
    Brindley AA, Raux E, Leech HK et al. A story of chelatase evolution—Identification and characterization of a small 13–15-kda “ancestral” cobaltochelatase (CbiX(s)) in the archaea. J Biol Chem 2003; 278:22388–22395.CrossRefPubMedGoogle Scholar
  52. 50.
    Wu CK, Dailey HA, Rose JP et al. The 2.0 A structure of human ferrochelatase, the terminal enzyme of heme biosynthesis. Nat Struct Biol 2001; 8:156–160.CrossRefPubMedGoogle Scholar
  53. 51.
    Dailey TA, Dailey HA. Identification of [2Fe-2S] clusters in microbial ferrochelatases. J Bacteriol 2002; 184:2460–2464.CrossRefPubMedGoogle Scholar
  54. 52.
    Schubert HL, Raux E, Wilson KS et al. Common chelatase design in the branched tetrapyrrole pathways of heme and anaerobic cobalamin synthesis. Biochemistry 1999; 38:10660–10669.CrossRefPubMedGoogle Scholar
  55. 53.
    Cornah JE, Roper JM, Singh DP et al. Measurement of ferrochelatase activity using a novel assay suggests that plastids are the major site of haem biosynthesis in both photosynthetic and nonphotosynthetic cells of pea (Pisum sativum L). Biochem J 2002; 362:423–432.CrossRefPubMedGoogle Scholar
  56. 54.
    Walker CJ, Yu GH, Weinstein JD. Comparative study of heme and Mg-protoporphyrin (monomethyl ester) biosynthesis in isolated pea chloroplasts: Effects of ATP and metal ions. Plant Physiol Biochem 1997; 35:213–221.Google Scholar
  57. 55.
    Walker CJ, Willows RD. Mechanism and regulation of Mg-chelatase. Biochem J 1997; 327:321–333.PubMedGoogle Scholar
  58. 56.
    Jensen PE, Reid JD, Hunter CN. Modification of cysteine residues in the ChlI and ChlH subunits of magnesium chelatase results in enzyme inactivation. Biochem J 2000; 352:435–441.CrossRefPubMedGoogle Scholar
  59. 57.
    Wilde A, Mikolajczyk S, Alawady A et al. The gun4 gene is essential for cyanobacterial porphyrin metabolism. FEBS Lett 2004; 571:119–123.CrossRefPubMedGoogle Scholar
  60. 58.
    Gibson LC, Marrison JL, Leech RM et al. A putative Mg chelatase subunit from Arabidopsis thaliana cv C24. Sequence and transcript analysis of the gene, import of the protein into chloroplasts, and in situ localization of the transcript and protein. Plant Physiol 1996; 111:61–71.CrossRefPubMedGoogle Scholar
  61. 59.
    Chow KS, Singh DP, Amanda RW et al. Two different genes encode ferrochelatase in Arabidopsis: Mapping, expression and subcellular targeting of the precursor proteins. Plant J 1998; 15:531–541.CrossRefPubMedGoogle Scholar
  62. 60.
    Janssen S. A guide to the Lhc genes and their relatives in Arabidopsis. Trend Plant Sci 1999; 4:236–240.CrossRefGoogle Scholar
  63. 61.
    Masuda T, Takamiya K. Novel insights into the enzymology, regulation and physiological functions of light-dependent protochlorophyllide oxidoreductase in angiosperms. Photosyn Res 2004; 81:1–29.CrossRefPubMedGoogle Scholar
  64. 62.
    Harper AL, von Gesjen SE, Linford AS et al. Chlorophyllide a oxygenase mRNA and protein levels correlate with the chlorophyll a/b ratio in Arabidopsis thaliana. Photosyn Res 2004; 79:149–159.CrossRefPubMedGoogle Scholar
  65. 63.
    Franklin KA, Linley PJ, Montgomery BL et al. Misregulation of tetrapyrrole biosynthesis in transgenic tobacco seedlings expressing mammalian biliverdin reductase. Plant J 2003; 35:717–728.CrossRefPubMedGoogle Scholar
  66. 64.
    Balmer Y, Koller A, del Val G et al. Proteomics gives insight into the regulatory function of chloroplast thioredoxins. Proc Natl Acad Sci USA 2003; 100:370–375.CrossRefPubMedGoogle Scholar
  67. 65.
    Yaronskaya E, Ziemann V, Walter G et al. Metabolic control of the tetrapyrrole biosynthetic pathway for porphyrin distribution in the barley mutant albostrians. Plant J 2003; 35:512–522.CrossRefPubMedGoogle Scholar
  68. 66.
    Kleffmann T, Russenberger D, von Zychlinski A et al. The Arabidopsis thaliana chloroplast proteome reveals pathway abundance and novel protein functions. Curr Biol 2004; 14:354–362.CrossRefPubMedGoogle Scholar
  69. 67.
    Moser J, Schubert WD, Beier V et al. V-shaped structure of glutamyl-tRNA reductase, the first enzyme of tRNA dependent tetrapyrrole biosynthesis. EMBO J 2001; 20:6583–6590.CrossRefPubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2009

Authors and Affiliations

  1. 1.School of Biological SciencesUniversity of SouthamptonSouthamptonUK
  2. 2.Department of Plant SciencesUniversity of CambridgeCambridgeUK

Personalised recommendations