Highlights in haem biosynthesis.

P M Jordan

doi:10.1016/0959-440x(94)90273-9

Home/Archive/PubMed

PubMed · 7712294

Highlights in haem biosynthesis.

P M Jordan

View original source ↗Export metadata ↓

Abstract

The haem biosynthesis pathway continues to provide surprises, from the first enzyme, 5-aminolaevulinic acid synthase, the mRNA of which contains an iron-responsive element, to the last, ferrochelatase, that contains an iron sulphur cluster. 5-Aminolaevulinate dehydratase from animals are zinc-dependent enzymes while those from plants require magnesium. The first X-ray structure of a haem synthesis enzyme, porphobilinogen deaminase, has not only yielded clues about the mechanism of tetrapyrrole assembly but has also provided insight into the molecular basis of the human disease acute intermittent porphyria. Evidence is growing to suggest that a previously unsuspected alternative haem pathway may exist.

Explore related subjects

5-Aminolevulinate Synthetase Amino Acid Sequence Animals Base Sequence Coproporphyrinogen Oxidase Heme Humans Hydroxymethylbilane Synthase Intramolecular Transferases Isomerases Models, Chemical Molecular Sequence Data Porphobilinogen Synthase Journal Article Research Support, Non-U.S. Gov't Review

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

P M Jordan. 1994. Highlights in haem biosynthesis.. https://doi.org/10.1016/0959-440x(94)90273-9

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2006

Decrease of hepatic delta-aminolevulinate dehydratase activity in an animal model of fatigue.

Fatigue can be defined physiologically as inability to maintain the expected power output. At present, no standard of fatigue are yet available. In order to find biomarkers of fatigue, we investigated the level of delta-aminolevulinic acid (ALA), the first intermediate metabolite in the heme biosynthetic pathway, in the plasma and urine of an animal model of fatigue. To prepare fatigued animals, we kept rats for 5 days in a cage filled with water to a height of 1.5 cm. As a result, the plasma and urinary ALA levels were increased in the fatigued animals as compared with those in the control animals. One day after the rats had been returned to their normal cages, these increased levels were restored to the control ones. We also examined the activity of the enzyme ALA dehydratase (ALAD), which is the second enzyme in the heme biosynthetic pathway, and ALAD gene expression during the fatigue and its recovery sessions. The ALAD activity, as well as its gene expression, in the liver of the fatigued animals was decreased as compared with those of the control animals. Both activity and gene expression of ALAD were recovered to their respective control levels after the rats had been allowed to rest in their normal cages for 1 day. Furthermore, the activity of ALA synthase (ALAS), the rate-limiting enzyme in the heme biosynthesis, in the liver was increased after the fatigue session for 5 days. Although this level of increase in the plasma concentration of ALA may not induce fatigue, increase in plasma and urinary ALA levels can be biomarkers of fatigue.

5-Aminolevulinate Synthetase↗

PubMed2006

Mechanism and substrate stereochemistry of 2-amino-3-oxobutyrate CoA ligase: implications for 5-aminolevulinate synthase and related enzymes.

The condensation process catalysed by 2-amino-3-oxobutyrate CoA ligase (KBL; also known as 2-amino-3-ketobutyrate ligase) involves the loss of the pro-R hydrogen atom of glycine and occurs with the inversion of stereochemistry; a similar scenario is envisaged for the condensation step of other alpha-oxoamine synthases.

5-Aminolevulinate Synthetase↗

PubMed2006

Histone acetyltransferase p300 regulates the transcription of human erythroid-specific 5-aminolevulinate synthase gene.

Erythroid-specific 5-aminolevulinate synthase (ALAS2) catalyzes the rate-limiting step in heme biosynthesis of erythroid cells. Here, we show that treatment of erythroid K562 cells with HDAC inhibitors sodium butyrate or Trichostatin A gave rise to a significant increase in ALAS2 gene transcripts, with a concurrent increase in acetylation level of histone H4 at the ALAS2 gene promoter. Histone acetyltransferase p300 bound withALAS2 promoter and overexpression of p300 increased both the promoter reporter expression and endogenous mRNA level of ALAS2. Additionally, two functional Sp1 sites located in ALAS2 promoter were identified. Both of the GATA-1 sites and all the Sp1 sites at the ALAS2 promoter contributed to the transcription synergistic action with p300. These data implicated a close relationship between the acetylation modification of histone at the ALAS2 promoter and the regulation of this gene. Meanwhile, this work identified that ALAS2 is a novel target gene for p300/CBP action as histone acetyltransferases.

5-Aminolevulinate Synthetase↗