RGD Reference Report - Comparative inhibition of hepatic hydroxymethylbilane synthase by both hard and soft metal cations. - Rat Genome Database

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Comparative inhibition of hepatic hydroxymethylbilane synthase by both hard and soft metal cations.

Authors: Farmer, D J  Hollebone, B R 
Citation: Farmer DJ and Hollebone BR, Can J Biochem Cell Biol. 1984 Jan;62(1):49-54. doi: 10.1139/o84-008.
RGD ID: 25394584
Pubmed: PMID:6732900   (View Abstract at PubMed)
DOI: DOI:10.1139/o84-008   (Journal Full-text)

The in vitro inhibition of hydroxymethylbilane synthase (EC 4.3.1.8, uroporphyrinogen I synthetase) obtained from livers of Sprague-Dawley rats has been studied with a wide range of di- and tri-valent metal ions. After purification by cell lysis, heat treatment, and centrifugation, the stable, soluble enzyme yielded sigmoidal inhibition curves with increasing concentrations of each of the 16 test ions. Using the negative logarithm of metal concentration for 50% inhibition (the pM50 value), the metal ions could be classified according to their Klopman hardness values. Very soft ions including Hg2+, intermediate ions including Cr3+, and very hard ions including Al3+ all yielded large pM50 values indicating strong inhibition. In comparison to known metal-ion chemical behaviour, these three ions could indicate three different types of inhibitory binding sites at or near the active site: Hg2+ corresponding to sulfur in cysteine, Cr3+ corresponding to nitrogen in histidine, and Al3+ corresponding to oxygen in carboxyl groups. The presence of the first two sites is also indicated by the pH dependence of activity.



Gene-Chemical Interaction Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
HMBSHumanaluminium ion decreases activityISOHmbs (Rattus norvegicus)Aluminium ion decreases activity of purified Hmbs proteinRGD 
HmbsRataluminium ion decreases activityEXP Aluminium ion decreases activity of purified Hmbs proteinRGD 
HmbsMousealuminium ion decreases activityISOHmbs (Rattus norvegicus)Aluminium ion decreases activity of purified Hmbs proteinRGD 
HMBSHumanbarium ion decreases activityISOHmbs (Rattus norvegicus)Barium ion decreases activity of purified Hmbs proteinRGD 
HmbsRatbarium ion decreases activityEXP Barium ion decreases activity of purified Hmbs proteinRGD 
HmbsMousebarium ion decreases activityISOHmbs (Rattus norvegicus)Barium ion decreases activity of purified Hmbs proteinRGD 
HMBSHumancalcium ion decreases activityISOHmbs (Rattus norvegicus)Calcium ion decreases activity of purified Hmbs proteinRGD 
HmbsRatcalcium ion decreases activityEXP Calcium ion decreases activity of purified Hmbs proteinRGD 
HmbsMousecalcium ion decreases activityISOHmbs (Rattus norvegicus)Calcium ion decreases activity of purified Hmbs proteinRGD 
HMBSHumanchromium ion decreases activityISOHmbs (Rattus norvegicus)Chromium ion decreases activity of purified Hmbs proteinRGD 
HmbsRatchromium ion decreases activityEXP Chromium ion decreases activity of purified Hmbs proteinRGD 
HmbsMousechromium ion decreases activityISOHmbs (Rattus norvegicus)Chromium ion decreases activity of purified Hmbs proteinRGD 
HMBSHumanlead ion decreases activityISOHmbs (Rattus norvegicus)Lead ion decreases activity of purified Hmbs proteinRGD 
HmbsRatlead ion decreases activityEXP Lead ion decreases activity of purified Hmbs proteinRGD 
HmbsMouselead ion decreases activityISOHmbs (Rattus norvegicus)Lead ion decreases activity of purified Hmbs proteinRGD 
HMBSHumanmagnesium ion decreases activityISOHmbs (Rattus norvegicus)Magnesium ion decreases activity of purified Hmbs proteinRGD 
HmbsRatmagnesium ion decreases activityEXP Magnesium ion decreases activity of purified Hmbs proteinRGD 
HmbsMousemagnesium ion decreases activityISOHmbs (Rattus norvegicus)Magnesium ion decreases activity of purified Hmbs proteinRGD 
HMBSHumanmercury dichloride decreases activityISOHmbs (Rattus norvegicus)Mercury dichloride decreases activity of purified Hmbs proteinRGD 
HmbsRatmercury dichloride decreases activityEXP Mercury dichloride decreases activity of purified Hmbs proteinRGD 
HmbsMousemercury dichloride decreases activityISOHmbs (Rattus norvegicus)Mercury dichloride decreases activity of purified Hmbs proteinRGD 
HMBSHumannickel ion decreases activityISOHmbs (Rattus norvegicus)Nickel ion decreases activity of purified Hmbs proteinRGD 
HmbsRatnickel ion decreases activityEXP Nickel ion decreases activity of purified Hmbs proteinRGD 
HmbsMousenickel ion decreases activityISOHmbs (Rattus norvegicus)Nickel ion decreases activity of purified Hmbs proteinRGD 
HMBSHumanzinc ion decreases activityISOHmbs (Rattus norvegicus)Zinc ion decreases activity of purified Hmbs proteinRGD 
HmbsRatzinc ion decreases activityEXP Zinc ion decreases activity of purified Hmbs proteinRGD 
HmbsMousezinc ion decreases activityISOHmbs (Rattus norvegicus)Zinc ion decreases activity of purified Hmbs proteinRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
HmbsRatporphyrin-containing compound biosynthetic process  IDA UrophorphyrinRGD 
HmbsRatporphyrin-containing compound metabolic process  IDA PorphobilinogenRGD 

Objects Annotated

Genes (Rattus norvegicus)
Hmbs  (hydroxymethylbilane synthase)

Genes (Mus musculus)
Hmbs  (hydroxymethylbilane synthase)

Genes (Homo sapiens)
HMBS  (hydroxymethylbilane synthase)


Additional Information