Hydroxymethylbilane synthase

This enzyme is also called porphobilinogen deaminase or hydroxymethylbilane synthase. 

HMBS hydroxymethylbilane-synthase, Intermediaries heptacarboxy-, hexacarboxy-and pentacarboxyporphyrins, MIM Nr Mendelian Inheritance in Man number, PCT porphyria cutanea tarda, Proto protoporphyrin IX, PV porphyria variegata, Uro uroporphyrin... 

If the patient is actually asymptomatic, but has a family history of acute porphyria or prior symptoms suspicious of acute porphyria, hydroxymethylbilane synthase (HMBS) activity, plasma scanning, and fecal porphyrins should be measured. These tests will reveal AIP, P V, and HC. As a small percentage of AIP families exhibit normal HMBS activity, PBG in a urine sample can be added. PBG determination can also performed as a first choice, if an acute porphyria is suspected. But if normal, it does not exclude acute porphyrias in asymptomatic phases. Furthermore, the existence of an acute porphyria is only proved if the value exceeds at least five times the upper limit of normal. 

Table 7.3.8 Standards used in the determination of hydroxymethylbilane synthase activity...

An acute disease caused by a deficiency in hydroxymethylbilane synthase. 

Hydroxymethylbilane synthase 1 Hydroxymethylbilane Acute intermittent porphyria (AD,11q23) J... 

Hydroxymethylbilane Synthase (EC 2.5.1.61), HMBS HMBS (also known as porphobilinogen [PEG] deaminase) is a cytoplasmic enzyme that catalyzes the formation of one molecule of the linear tetrapyrrole 1-hydroxymethylbilane (HMB also known as preuroporphyrinogen) from four molecules of PEG with the release of four molecules of ammonia. The former enzyme committee designation for HMBS was EC 4.3.1.8, but in 2003 the enzyme was redesignated as EC 2.5.1.61. The enzyme has two molecules of its own substrate PEG, attached covalently to the apoenzyme as a prosthetic group. The enzyme is susceptible to allosteric inhibition by intermediates further down the heme biosynthetic pathway, notably coproporphyrinogen-III and protoporphyrinogen-IX. 

Wright DJ, Lim CK. Simultaneous determination of hydroxymethylbilane synthase and uroporphyrino-gen-III synthase in erythrocytes by HPLC. Biochem J 1983 213 85-8. 

Scheme 10. The relationship between hydroxymethylbilane synthase and uro gen III synthase...

Fig. 1. Ribbon representation of hydroxymethylbilane synthase from . coli [44]. Domains 1,2 and 3 are in yellow, blue and magenta respectively. The cofactor, in green, is here in its active reduced form...

---