Hydroxymethylbilane synthase HMBS

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. 

Now, although details are lacking, it appears that PBG molecules condense under the influence of PBG deaminase (hydroxymethylbilane synthase [HMBS], EC 2.5.1.61) and a growing chain of porphyrinogens evolves. Interestingly, it has been reported that acute intermittent porphyria (AIP) is an autosomal dominant inherited disease caused by a decreased activity of HMBS. The disease, porphyria. 

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... 

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. 

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