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Gene Review

HEM1  -  5-aminolevulinate synthase

Saccharomyces cerevisiae S288c

Synonyms: 5-aminolevulinate synthase, mitochondrial, 5-aminolevulinic acid synthase, CYD1, Delta-ALA synthase, Delta-aminolevulinate synthase, ...
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High impact information on HEM1

  • Interestingly, heme also potentiates binding of the yeast transcriptional activator HAP1 to DNA and inhibits mitochondrial import of the mammalian delta-aminolevulinate synthase (ALAS) and the catalytic activity of the reticulocyte kinase, HRI [1].
  • First is a second activation system acting at a site close to the HAP2-HAP3 target sequence that keeps HEM1 turned on under conditions of heme deficiency [2].
  • Oxygen appeared to act at the level of transcription through heme, since the addition of heme restored an aerobic pattern of transcription to anaerobically grown cells and the effect of anaerobiosis on COX5 transcription was reproduced in strains containing a mutation in the heme-biosynthetic pathway (hem1) [3].
  • The amino acid sequence deduced from the DNA sequence of HEM1 showed that the amino-terminal region of delta-aminolevulinate synthase was largely hydrophobic, with a few basic residues interspersed [4].
  • We found that the absence of heme, due to a deletion in the gene that encodes delta-aminolevulinic acid synthase (HEM1), resulted in decreased transcription of genes belonging to both the iron and copper regulons, but not the zinc regulon [5].

Biological context of HEM1

  • An important element required for expression of HEM3 has been localized to a small region that contains a sequence homologous to the HAP2-3-4 binding sites of several genes including HEM1 [6].
  • Transformation of an rhm1 strain with a multicopy plasmid containing the cloned HEM1 gene restored normal levels of 5-aminolevulinate synthase activity, but intracellular 5-aminolevulinate was increased to only 9 to 10% of normal [7].
  • Using double mutants in the HEM1 gene and individual ARE genes we demonstrated that the relative contribution of these two enzymes to sterol esterification was dependent on cellular heme status [8].
  • Yeast cells almost completely deficient in all cytochromes were obtained by introducing two defective nuclear genes, cyd1 and cyc4, into the same haploid strain [9].
  • Mutant strain DA3-RS3/68 contained mutant gene rhm1, which segregated independently of hem1 and cyc4 during meiosis [7].

Anatomical context of HEM1


Associations of HEM1 with chemical compounds


Regulatory relationships of HEM1

  • These findings suggest that HEM3 expression is regulated in the same manner as that of HEM1 which encodes the first enzyme of the heme biosynthetic pathway [6].

Other interactions of HEM1

  • We propose that the absence of functional Asc1p allows the growth of hap1-hem1- cells by reducing the efficiency of translation [14].
  • We observed that sterol uptake was then comparable with that obtained with a sterol importing hem1 mutant, although the heme status of the strain was not modified in a process which still occurs when the cells are not growing [15].
  • The effect of delta-aminolevulinate on catalase T-messenger RNA levels in delta-aminolevulinate synthase-defective mutants of Saccharomyces cerevisiae [16].

Analytical, diagnostic and therapeutic context of HEM1

  • In vitro translation of mRNA hybrid-selected by the cloned HEM1 gene, or of total RNA followed by immunoprecipitation with anti-(ALA synthase) antibody yielded a single polypeptide of higher molecular mass than the purified ALA synthase [17].


  1. Heme binds to a short sequence that serves a regulatory function in diverse proteins. Zhang, L., Guarente, L. EMBO J. (1995) [Pubmed]
  2. Constitutive expression of the yeast HEM1 gene is actually a composite of activation and repression. Keng, T., Guarente, L. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  3. Inverse regulation of the yeast COX5 genes by oxygen and heme. Hodge, M.R., Kim, G., Singh, K., Cumsky, M.G. Mol. Cell. Biol. (1989) [Pubmed]
  4. The nine amino-terminal residues of delta-aminolevulinate synthase direct beta-galactosidase into the mitochondrial matrix. Keng, T., Alani, E., Guarente, L. Mol. Cell. Biol. (1986) [Pubmed]
  5. Inhibition of heme biosynthesis prevents transcription of iron uptake genes in yeast. Crisp, R.J., Pollington, A., Galea, C., Jaron, S., Yamaguchi-Iwai, Y., Kaplan, J. J. Biol. Chem. (2003) [Pubmed]
  6. Structure and regulation of yeast HEM3, the gene for porphobilinogen deaminase. Keng, T., Richard, C., Larocque, R. Mol. Gen. Genet. (1992) [Pubmed]
  7. Isolation and characterization of a new mutant of Saccharomyces cerevisiae with altered synthesis of 5-aminolevulinic acid. Carvajal, E., Panek, A.D., Mattoon, J.R. J. Bacteriol. (1990) [Pubmed]
  8. Heme-regulated expression of two yeast acyl-CoA:sterol acyltransferases is involved in the specific response of sterol esterification to anaerobiosis. Valachovic, M., Klobucníková, V., Griac, P., Hapala, I. FEMS Microbiol. Lett. (2002) [Pubmed]
  9. Regulation of mitochondrial biogenesis: enzymatic changes in cytochrome-deficient yeast mutants requiring delta-aminolevulinic acid. Woods, R.A., Sanders, H.K., Briquet, M., Foury, F., Drysdale, B.E., Mattoon, J.R. J. Biol. Chem. (1975) [Pubmed]
  10. The presence of the iron-sulfur protein (subunit V) of complex III in mitochondria of heme-deficient yeast cells lacking iron-sulfur clusters detectable by electron paramagnetic resonance. Lin, C.I., Ohnishi, T., Clejan, L., Beattie, D.S. Eur. J. Biochem. (1983) [Pubmed]
  11. Yeast mutants deficient in heme biosynthesis and a heme mutant additionally blocked in cyclization of 2,3-oxidosqualene. Gollub, E.G., Liu, K.P., Dayan, J., Adlersberg, M., Sprinson, D.B. J. Biol. Chem. (1977) [Pubmed]
  12. Structural discrimination in the sparking function of sterols in the yeast Saccharomyces cerevisiae. Lorenz, R.T., Casey, W.M., Parks, L.W. J. Bacteriol. (1989) [Pubmed]
  13. delta-aminolaevulinic acid modulates the resistance to fluconazole in a hem1 mutant of Saccharomyces cerevisiae. Kontoyiannis, D.P., May, G.S. J. Antimicrob. Chemother. (2000) [Pubmed]
  14. The transcriptional regulator Hap1p (Cyp1p) is essential for anaerobic or heme-deficient growth of Saccharomyces cerevisiae: Genetic and molecular characterization of an extragenic suppressor that encodes a WD repeat protein. Chantrel, Y., Gaisne, M., Lions, C., Verdière, J. Genetics (1998) [Pubmed]
  15. SUT1 is a putative Zn[II]2Cys6-transcription factor whose upregulation enhances both sterol uptake and synthesis in aerobically growing Saccharomyces cerevisiae cells. Ness, F., Bourot, S., Régnacq, M., Spagnoli, R., Bergès, T., Karst, F. Eur. J. Biochem. (2001) [Pubmed]
  16. The effect of delta-aminolevulinate on catalase T-messenger RNA levels in delta-aminolevulinate synthase-defective mutants of Saccharomyces cerevisiae. Richter, K., Ammerer, G., Hartter, E., Ruis, H. J. Biol. Chem. (1980) [Pubmed]
  17. The nucleotide sequence of the HEM1 gene and evidence for a precursor form of the mitochondrial 5-aminolevulinate synthase in Saccharomyces cerevisiae. Urban-Grimal, D., Volland, C., Garnier, T., Dehoux, P., Labbe-Bois, R. Eur. J. Biochem. (1986) [Pubmed]
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