Biochemical and computational approaches to improve the clinical treatment of dopa decarboxylase-related diseases: An overview

Open Biochemistry Journal

Volumn 6, Issue , 2012, Pages 131-138

  Cellini, Barbara ^a   Montioli, Riccardo ^a   Oppici, Elisa ^a   Voltattorni, Carla Borri ^a  

^a UNIVERSITY OF VERONA   (Italy)

Author keywords

AADC deficiency; Dopa decarboxylase; Parkinson's disease; Pyridoxal 5' phosphate

Indexed keywords

AROMATIC LEVO AMINO ACID DECARBOXYLASE; BENSERAZIDE; BROMOCRIPTINE; CARBIDOPA; DOPA DECARBOXYLASE INHIBITOR; DOPAMINE RECEPTOR STIMULATING AGENT; LEVODOPA; MOCLOBEMIDE; MONOAMINE OXIDASE B INHIBITOR; NEUROTRANSMITTER; PERGOLIDE; PRAMIPEXOLE; PYRIDOXINE; ROPINIROLE; SELEGILINE; TRANYLCYPROMINE;

AROMATIC AMINO ACID DECARBOXYLASE DEFICIENCY; ARTICLE; AUTONOMIC NEUROPATHY; BRADYKINESIA; CRYSTAL STRUCTURE; DECARBOXYLATION; DISEASE SEVERITY; DOPAMINERGIC NERVE CELL; DRUG EFFICACY; DRUG SAFETY; ENZYME DEFICIENCY; GASTROINTESTINAL HEMORRHAGE; GENE MUTATION; HEART ARRHYTHMIA; HUMAN; HYPOTENSION; MENTAL DISEASE; METABOLIC DISORDER; NAUSEA; NERVE CELL DEGENERATION; NONHUMAN; OCULOGYRIC CRISIS; PARKINSON DISEASE; PRACTICE GUIDELINE; PRIORITY JOURNAL; RIGIDITY; SUBSTANTIA NIGRA; TREMOR;

EID: 84873872722     PISSN: None     EISSN: 1874091X     Source Type: Journal    
DOI: 10.2174/1874091X01206010131     Document Type: Article

References (81)

1. Contestabile, R.; Paiardini, A.; Pascarella, S.; di Salvo, M.L.; D'Aguanno, S.; Bossa, F. l-Threonine aldolase, serine hydroxymethyltransferase and fungal alanine racemase. A subgroup of strictly related enzymes specialized for different functions. Eur. J. Biochem., 2001, 268(24), 6508-6525.
2. Christen P.; Metzler D.E. Transaminases; Wiley: New York, 1985.
3. Keller, J.W.; Baurick, K.B.; Rutt, G.C.; O'Malley, M.V.; Sonafrank, N.L.; Reynolds, R.A.; Ebbesson, L.O.; Vajdos, F.F. Pseudomonas cepacia 2,2-dialkylglycine decarboxylase. Sequence and expression in Escherichia coli of structural and repressor genes. J. Biol. Chem., 1990, 265(10), 5531-5539.
4. Kaiser, J.T.; Bruno, S.; Clausen, T.; Huber, R.; Schiaretti, F.; Mozzarelli, A.; Kessler, D. Snapshots of the cystine lyase C-DES during catalysis. Studies in solution and in the crystalline state. J. Biol. Chem., 2003, 278(1), 357-365.
5. Miles, E.W. Tryptophan synthase: a multienzyme complex with an intramolecular tunnel. Chem. Rec., 2001, 1(2), 140-151.
6. Brzovic, P.; Holbrook, E.L.; Greene, R.C.; Dunn, M.F. Reaction mechanism of Escherichia coli cystathionine gamma-synthase: direct evidence for a pyridoxamine derivative of vinylglyoxylate as a key intermediate in pyridoxal phosphate dependent gamma-elimination and gamma-replacement reactions. Biochemistry, 1990, 29(2), 442-451.
7. Amadasi, A.; Bertoldi, M.; Contestabile, R.; Bettati, S.; Cellini, B.; di Salvo, M.L.; Borri-Voltattorni, C.; Bossa, F.; Mozzarelli, A. Pyridoxal 5'-phosphate enzymes as targets for therapeutic agents. Curr. Med. Chem., 2007, 14(12), 1291-1324.
8. Silverman, R.B. From basic science to blockbuster drug: the discovery of Lyrica. Angew Chem. Int. Ed. Engl., 2008, 47(19), 3500-3504.
9. Chu, L.; Holt, S.C. Purification and characterization of a 45 kDa hemolysin from Treponema denticola ATCC 35404. Microb. Pathog., 1994, 16(3), 197-212.
10. Bertoldi, M.; Gonsalvi, M.; Contestabile, R.; Voltattorni, C.B. Mutation of tyrosine 332 to phenylalanine converts dopa decarboxylase into a decarboxylation-dependent oxidative deaminase. J. Biol. Chem., 2002, 277(39), 36357-36362.
11. Fenn, T.D.; Stamper, G.F.; Morollo, A.A.; Ringe, D. A side reaction of alanine racemase: transamination of cycloserine. Biochemistry, 2003, 42(19), 5775-5783.
12. Seiler, N. Thirty years of polyamine-related approaches to cancer therapy. Retrospect and prospect. Part 1. Selective enzyme inhibitors. Curr. Drug. Target, 2003, 4(7), 537-564.
13. Cotter, P.D.; Baumann, M.; Bishop, D.F. Enzymatic defect in "X-linked" sideroblastic anemia: molecular evidence for erythroid delta-aminolevulinate synthase deficiency. Proc. Natl. Acad. Sci. USA., 1992, 89(9), 4028-4032.
14. Medina-Kauwe, L.K.; Tobin, A.J.; De Meirleir, L.; Jaeken, J.; Jakobs, C.; Nyhan, W.L.; Gibson, K.M. 4-Aminobutyrate aminotransferase (GABA-transaminase) deficiency. J. Inherit. Metab. Dis., 1999, 22(4), 414-427.
15. Zhu, W.; Lin, A.; Banerjee, R. Kinetic properties of polymorphic variants and pathogenic mutants in human cystathionine gamma-lyase. Biochemistry, 2008, 47(23), 6226-6232.
16. Montioli, R.; Cellini, B.; Borri Voltattorni, C. Molecular insights into the pathogenicity of variants associated with the aromatic amino acid decarboxylase deficiency. J. Inherit. Metab. Dis., 2011, 34(6), 1213-1224.
17. Cellini, B.; Oppici, E.; Paiardini, A.; Montioli, R. Molecular insights into primary hyperoxaluria type 1 pathogenesis. Front. Biosci., 2012, 17, 621-634.
18. Brody, L.C.; Mitchell, G.A.; Obie, C.; Michaud, J.; Steel, G.; Fontaine, G.; Robert, M.F.; Sipila, I.; Kaiser-Kupfer, M.; Valle, D. Ornithine delta-aminotransferase mutations in gyrate atrophy. Allelic heterogeneity and functional consequences. J. Biol. Chem., 1992, 267(5), 3302-3307.
19. Pittman, A.M.; Lage, M.D.; Poltoratsky, V.; Vrana, J.D.; Paiardini, A.; Roncador, A.; Cellini, B.; Hughes, R.M.; Tucker, C.L. Rapid Profiling of Disease Alleles Using a Tunable Reporter of Protein Misfolding. Genetics, 2012; 192(3): 831-842.
20. Cellini, B.; Bertoldi, M.; Montioli, R.; Paiardini, A.; Borri Voltattorni, C. Human wild-type alanine:glyoxylate aminotrans-ferase and its naturally occurring G82E variant: functional proper-ties and physiological implications. Biochem. J., 2007, 408(1), 39-50.
21. Cellini, B.; Montioli, R.; Bianconi, S.; Lopez-Alonso, J.P.; Voltattorni, C.B. Construction, purification and characterization of untagged human liver alanine-glyoxylate aminotransferase expressed in Escherichia coli. Protein. Pept. Lett., 2008, 15(2), 153-159.
22. Cellini, B.; Montioli, R.; Paiardini, A.; Lorenzetto, A.; Voltattorni, C.B. Molecular Insight into the Synergism between the Minor Allele of Human Liver Peroxisomal Alanine:Glyoxylate Aminotransferase and the F152I Mutation. J. Biol. Chem., 2009, 284(13), 8349-8358.
23. Cellini, B.; Montioli, R.; Paiardini, A.; Lorenzetto, A.; Maset, F.; Bellini, T.; Oppici, E.; Voltattorni, C.B. Molecular defects of the glycine 41 variants of alanine glyoxylate aminotransferase associated with primary hyperoxaluria type I. Proc. Natl. Acad. Sci. USA., 2010, 107(7), 2896-2901.
24. Cellini, B.; Lorenzetto, A.; Montioli, R.; Oppici, E.; Voltattorni, C.B. Human liver peroxisomal alanine:glyoxylate aminotransferase: Different stability under chemical stress of the major allele, the minor allele, and its pathogenic G170R variant. Biochimie, 2010, 92(12), 1801-1811.
25. Cellini, B.; Montioli, R.; Voltattorni, C.B. Human liver peroxisomal alanine:glyoxylate aminotransferase: characterization of the two allelic forms and their pathogenic variants. Biochim. Biophys. Acta, 2011, 1814(11), 1577-1584.
26. Oppici, E.; Montioli, R.; Lorenzetto, A.; Bianconi, S.; Borri Voltattorni, C.; Cellini, B. Biochemical analyses are instrumental in identifying the impact of mutations on holo and/or apo-forms and on the region(s) of alanine:glyoxylate aminotransferase variants associated with primary hyperoxaluria type I. Mol. Genet. Metab., 2012, 105(1), 132-140.
27. Sen, S.; Banerjee, R. A pathogenic linked mutation in the catalytic core of human cystathionine beta-synthase disrupts allosteric regulation and allows kinetic characterization of a full-length dimer. Biochemistry, 2007, 46(13), 4110-4116.
28. Singh, S.; Madzelan, P.; Stasser, J.; Weeks, C.L.; Becker, D.; Spiro, T.G.; Penner-Hahn, J.; Banerjee, R. Modulation of the heme electronic structure and cystathionine beta-synthase activity by second coordination sphere ligands: The role of heme ligand switching in redox regulation. J. Inorg. Biochem., 2009, 103(5), 689-697.
29. Kozich, V.; Sokolova, J.; Klatovska, V.; Krijt, J.; Janosik, M.; Jelinek, K.; Kraus, J.P. Cystathionine beta-synthase mutations: effect of mutation topology on folding and activity. Hum. Mutat., 2010, 31(7), 809-819.
30. di Salvo, M.L.; Contestabile, R.; Safo, M.K. Vitamin B(6) salvage enzymes: mechanism, structure and regulation. Biochim. Biophys. Acta, 2011, 1814(11), 1597-1608.
31. di Salvo, M.L.; Safo, M.K.; Contestabile, R. Biomedical aspects of pyridoxal 5'-phosphate availability. Front. Biosci. (Elite Ed.), 2012, 4, 897-913.
32. Gandhi, A.K.; Desai, J.V.; Ghatge, M.S.; di Salvo, M.L.; Di Biase, S.; Danso-Danquah, R.; Musayev, F.N.; Contestabile, R.; Schirch, V.; Safo, M.K. Crystal structures of human pyridoxal kinase in complex with the neurotoxins, ginkgotoxin and theophylline: insights into pyridoxal kinase inhibition. PLoS One, 2012, 7(7), e40954.
33. Hayashi, H.; Mizuguchi, H.; Kagamiyama, H. Rat liver aromatic L-amino acid decarboxylase: spectroscopic and kinetic analysis of the coenzyme and reaction intermediates. Biochemistry, 1993, 32(3), 812-818.
34. Moore, P.S.; Dominici, P.; Borri Voltattorni, C. Cloning and expression of pig kidney dopa decarboxylase: comparison of the naturally occurring and recombinant enzymes. Biochem. J., 1996, 315(Pt 1), 249-256.
35. Voltattorni, C.B.; Minelli, A.; Turano, C. Spectral properties of the coenzyme bound to DOPA decarboxylase from pig kidney. FEBS Lett., 1971, 17(2), 231-235.
36. Voltattorni, C.B.; Minelli, A.; Dominici, P. Interaction of aromatic amino acids in D and L forms with 3,4-dihydroxyphenylalanine decarboxylase from pig kidney. Biochemistry, 1983, 22(9), 2249-2254.
37. Dominici, P.; Tancini, B.; Borri Voltattorni, C. Chemical modification of pig kidney 3,4-dihydroxyphenylalanine decarboxylase with diethyl pyrocarbonate. Evidence for an essential histidyl residue. J. Biol. Chem., 1985, 260(19), 10583-10589.
38. Tancini, B.; Dominici, P.; Simmaco, M.; Schinina, M. E.; Barra, D.; Voltattorni, C. B., Limited tryptic proteolysis of pig kidney 3,4-dihydroxyphenylalanine decarboxylase. Arch. Biochem. Biophys., 1988, 260 (2), 569-576.
39. Maras, B.; Dominici, P.; Barra, D.; Bossa, F.; Voltattorni, C.B. Pig kidney 3,4-dihydroxyphenylalanine (dopa) decarboxylase. Primary structure and relationships to other amino acid decarboxylases. Eur. J. Biochem., 1991, 201(2), 385-391.
40. Bertoldi, M.; Moore, P.S.; Maras, B.; Dominici, P.; Voltattorni, C.B. Mechanism-based inactivation of dopa decarboxylase by serotonin. J. Biol. Chem., 1996, 271(39), 23954-23959.
41. Bertoldi, M.; Dominici, P.; Moore, P.S.; Maras, B.; Voltattorni, C.B. Reaction of dopa decarboxylase with alpha-methyldopa leads to an oxidative deamination producing 3,4-dihydroxyphenylacetone, an active site directed affinity label. Biochemistry, 1998, 37(18), 6552-6561.
42. Bertoldi, M.; Voltattorni, C.B. Multiple roles of the active site lysine of Dopa decarboxylase. Arch. Biochem. Biophys., 2009, 488(2), 130-139.
43. Burkhard, P.; Dominici, P.; Borri-Voltattorni, C.; Jansonius, J.N.; Malashkevich, V.N. Structural insight into Parkinson's disease treatment from drug-inhibited DOPA decarboxylase. Nat. Struct. Biol., 2001, 8(11), 963-967.
44. Fukumoto, Y.; Tanase, S.; Nagashima, F.; Ueda, S.; Ikegami, K.; Morino, Y. Structural and functional role of the amino-terminal region of porcine cytosolic aspartate aminotransferase. Catalytic and structural properties of enzyme derivatives truncated on the amino-terminal side. J. Biol. Chem., 1991, 266(7), 4187-4193.
45. Kravchuk, Z.; Tsybovsky, Y.; Koivulehto, M.; Vlasov, A.; Chumanevich, A.; Battchikova, N.; Martsev, S.; Korpela, T. Truncated aspartate aminotransferase from alkalophilic Bacillus circulans with deletion of N-terminal 32 amino acids is a non-functional monomer in a partially structured state. Protein. Eng., 2001, 14(4), 279-285.
46. Montioli, R.; Fargue, S.; Lewin, J.; Zamparelli, C.; Danpure, C.J.; Borri Voltattorni, C.; Cellini, B. The N-terminal extension is essential for the formation of the active dimeric structure of liver peroxisomal alanine:glyoxylate aminotransferase. Int. J. Biochem. Cell. Biol., 2012, 44(3), 536-546.
47. Giardina, G.; Montioli, R.; Gianni, S.; Cellini, B.; Paiardini, A.; Voltattorni, C.B.; Cutruzzola, F. Open conformation of human DOPA decarboxylase reveals the mechanism of PLP addition to Group II decarboxylases. Proc. Natl. Acad. Sci. USA., 2011, 108(51), 20514-20519.
48. Hauser, R.A. Levodopa: past, present, and future. Eur. Neurol., 2009, 62(1), 1-8.
49. Schwartz, D.E.; Brandt, R. Pharmacokinetic and metabolic studies of the decarboxylase inhibitor benserazide in animals and man. Arzneimittelforschung, 1978, 28(2), 302-307.
50. Borri-Voltattorni, C.; Minelli, A.; Borri, P. Interaction of N-(DL-seryl)N'-(2,3,4-trihydroxybenzyl)-hydrazine with L-dopa decarboxylase from pig kidney. Experientia, 1977, 33(2), 158-160.
51. Borri Voltattorni, C.; Minelli, A.; Borri, P. The interaction of 2,3,4-trihydroxybenzylhydrazine with DOPA decarboxylase from pig kidney. Life Sci., 1981, 28(1), 103-108.
52. Bender, D.A.; Earl, C.J.; Lees, A.J. Niacin depletion in Parkinsonian patients treated with L-dopa, benserazide and carbidopa. Clin. Sci., 1979, 56(1), 89-93.
53. Bender, D.A. Effects of benserazide, carbidopa and isoniazid administration on tryptophan-nicotinamide nucleotide metabolism in the rat. Biochem. Pharmacol., 1980, 29(15), 2099-2104.
54. Bender, D.A. Inhibition in vitro of the enzymes of the oxidative pathway of tryptophan metabolism and of nicotinamide nucleotide synthesis by benserazide, carbidopa and isoniazid. Biochem. Pharmacol., 1980, 29(5), 707-712.
55. McCormick, D.B.; Gregory, M.E.; Snell, E.E. Pyridoxal phosphokinases. I. Assay, distribution, I. Assay, distribution, purification, and properties. J. Biol. Chem., 1961, 236, 2076-2084.
56. Ebadi, M.S.; Russell, R.L.; McCoy, E.E. The inverse relationship between the activity of pyridoxal kinase and the level of biogenic amines in rabbit brain. J. Neurochem., 1968, 15(7), 659-665.
57. Allain, P.; Le Bouil, A.; Cordillet, E.; Le Quay, L.; Bagheri, H.; Montastruc, J.L. Sulfate and cysteine levels in the plasma of patients with Parkinson's disease. Neurotoxicology, 1995, 16(3), 527-529.
58. Kuhn, W.; Roebroek, R.; Blom, H.; van Oppenraaij, D.; Muller, T. Hyperhomocysteinaemia in Parkinson's disease. J. Neurol., 1998, 245(12), 811-812.
59. Miller, J.W.; Selhub, J.; Nadeau, M.R.; Thomas, C.A.; Feldman, R.G.; Wolf, P.A. Effect of L-dopa on plasma homocysteine in PD patients: relationship to B-vitamin status. Neurology, 2003, 60(7), 1125-1129.
60. Daidone, F.; Montioli, R.; Paiardini, A.; Cellini, B.; Macchiarulo, A.; Giardina, G.; Bossa, F.; Borri Voltattorni, C. Identification by virtual screening and in vitro testing of human DOPA decarboxylase inhibitors. PLoS One, 2012, 7(2), e31610.
61. Hyland, K.; Clayton, P.T. Aromatic amino acid decarboxylase deficiency in twins. J. Inherit. Metab. Dis., 1990, 13(3), 301-304.
62. Brun, L.; Ngu, L.H.; Keng, W.T.; Ch'ng, G.S.; Choy, Y.S.; Hwu, W.L.; Lee, W.T.; Willemsen, M.A.; Verbeek, M.M.; Wassenberg, T.; Regal, L.; Orcesi, S.; Tonduti, D.; Accorsi, P.; Testard, H.; Abdenur, J.E.; Tay, S.; Allen, G.F.; Heales, S.; Kern, I.; Kato, M.; Burlina, A.; Manegold, C.; Hoffmann, G.F.; Blau, N. Clinical and biochemical features of aromatic L-amino acid decarboxylase deficiency. Neurology, 2010, 75(1), 64-71.
63. Hyland, K.; Surtees, R.A.; Rodeck, C.; Clayton, P.T. Aromatic L-amino acid decarboxylase deficiency: clinical features, diagnosis, and treatment of a new inborn error of neurotransmitter amine synthesis. Neurology, 1992, 42(10), 1980-1988.
64. Hyland, K.; Clayton, P.T. Aromatic L-amino acid decarboxylase deficiency: diagnostic methodology. Clin. Chem., 1992, 38(12), 2405-2410.
65. Allen, G.F.; Land, J.M.; Heales, S.J. A new perspective on the treatment of aromatic L-amino acid decarboxylase deficiency. Mol. Genet. Metab., 2009, 97(1), 6-14.
66. Hwu, W.L.; Muramatsu, S.; Tseng, S.H.; Tzen, K.Y.; Lee, N.C.; Chien, Y.H.; Snyder, R.O.; Byrne, B.J.; Tai, C.H.; Wu, R.M. Gene therapy for aromatic L-amino acid decarboxylase deficiency. Sci. Transl. Med., 2012, 4(134), 134ra61.
67. Bertoldi, M.; Frigeri, P.; Paci, M.; Voltattorni, C.B. Reaction specificity of native and nicked 3,4-dihydroxyphenylalanine decarboxylase. J. Biol. Chem., 1999, 274(9), 5514-5521.
68. Chang, Y.T.; Mues G.; Mcpherson J.; Bedell J.L. Mutations in the human aromatic L-aminoacid decarboxylase gene. J. Inherit. Metab. Dis., 1998; 21(2), 4.
69. Wang, J.; Hegele, R.A. Genomic basis of cystathioninuria (MIM 219500) revealed by multiple mutations in cystathionine gamma-lyase (CTH). Hum. Genet., 2003, 112(4), 404-408.
70. Jaeken, J.; Casaer, P.; de Cock, P.; Corbeel, L.; Eeckels, R.; Eggermont, E.; Schechter, P.J.; Brucher, J.M. Gamma-aminobutyric acid-transaminase deficiency: a newly recognized inborn error of neurotransmitter metabolism. Neuropediatrics, 1984, 15(3), 165-169.
71. Ercan-Sencicek, A.G.; Stillman, A.A.; Ghosh, A.K.; Bilguvar, K.; O'Roak, B.J.; Mason, C.E.; Abbott, T.; Gupta, A.; King, R.A.; Pauls, D.L.; Tischfield, J.A.; Heiman, G.A.; Singer, H.S.; Gilbert, D.L.; Hoekstra, P.J.; Morgan, T.M.; Loring, E.; Yasuno, K.; Fernandez, T.; Sanders, S.; Louvi, A.; Cho, J.H.; Mane, S.; Colangelo, C.M.; Biederer, T.; Lifton, R.P.; Gunel, M.; State, M.W. L-histidine decarboxylase and Tourette's syndrome. New Engl. J. Med., 2010, 362(20), 1901-1908.
72. Tada, K.; Kure, S. Non-ketotic hyperglycinaemia: molecular lesion, diagnosis and pathophysiology. J. Inherit. Metab. Dis., 1993, 16(4), 691-703.
73. Dawkins, J.L.; Hulme, D.J.; Brahmbhatt, S.B.; Auer-Grumbach, M.; Nicholson, G.A. Mutations in SPTLC1, encoding serine palmitoyltransferase, long chain base subunit-1, cause hereditary sensory neuropathy type I. Nat. Genet., 2001, 27(3), 309-312.
74. Finkelstein, J. D.; Mudd, S.H.; Irreverre, F.; Laster, L. Homocystinuria Due to Cystathionine Synthetase Deficiency: The Mode of Inheritance. Science, 1964, 146(3645), 785-787.
75. Shih, V.E.; Berson, E.L.; Mandell, R.; Schmidt, S.Y. Ornithine ketoacid transaminase deficiency in gyrate atrophy of the choroid and retina. Am. J. Hum. Genet., 1978, 30(2), 174-179.
76. Danpure, C.J.; Jennings, P.R. Peroxisomal alanine:glyoxylate aminotransferase deficiency in primary hyperoxaluria type I. FEBS Lett., 1986, 201(1), 20-24.
77. Elsea, S. H.; Juyal, R.C.; Jiralerspong, S.; Finucane, B.M.; Pandolfo, M.; Greenberg, F.; Baldini, A.; Stover, P.; Patel, P.I. Haploinsufficiency of cytosolic serine hydroxymethyltransferase in the Smith-Magenis syndrome. Am. J. Hum. Genet., 1995, 57(6), 1342-1350.
78. Daw k.; Ujihara N.; Atkinson M.; A.C.; A. P. Glutamic Acid Decarboxylase Autoantibodies in Stiff-Man Syndrome and Insulin-Dependent Diabetes Mellitus Exhibit Similarities and Differences in Epitope Recognition. J. Immunol., 1996, (156), 818-825.
79. Natt, E.; Kida, K.; Odievre, M.; Di Rocco, M.; Scherer, G. Point mutations in the tyrosine aminotransferase gene in tyrosinemia type II. Proc. Natl. Acad. Sci. USA., 1992, 89(19), 9297-9301.
80. Tada, K.; Yokoyama, Y.; Nakagawa, H.; Yoshida, T.; Arakawa, T. Vitamin B6 dependent xanthurenic aciduria. Tohoku. J. Exp. Med., 1967, 93(2), 115-124.
81. Takaku, F.; Nakao, K. Delta-aminolevulinic acid synthetase activity in erythroblasts of patients with sideroblastic anemia. Life Sci. II, 1971, 10(13), 721-726.