Hydroxymethylbilane activity

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...

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...

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. 

Scheme 14.28. A representation of a pathway that accounts for the formation of uroporphyrinogen III from hydroxymethylbilane. Presumably, the hydroxyl group is activated for displacement, although the details of that activation are not yet known.

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