Hydroxymethyl bilane

This enzyme [EC 4.3.1.8], also known as hydroxymethyl-bilane synthase, catalyzes the dipyrromethane-depen-dent reaction of four porphobilinogen molecules with water to produce hydroxymethylbilane and four molecules of ammonia. In the presence of a second enzyme, uroporphyrinogen-III synthase [EC 4.2.1.75], the product is cycUzed to form uroporphyrinogen-III. 

Affected enzyme ALA-dehy- dratase Hydroxymethyl-bilane synthase Uroporphyrinogen III synthase Uroporphyrinogen decarboxylase Coproporphyrinogen oxidase Protoporphyrinogen oxidase Ferrochelatase... 

It is important to note that uroporphyrinogen III is an asymmetric compound with respect to its side chains. In the absence of uroporphyrinogen III cosynthase, hydroxymethyl bilane is converted nonenzymatically to the symmet-... 

Uroporphyrin I and coproporphyrin I will be present in the urine. In the absence of uroporphyrinogen cosynthase, hydroxymethyl bilane will spontaneously cyclyze into uroporphyrinogen I. Some of it will be oxidized to uroporphyrin I. Some will be decarboxylated by uroporphyrinogen decarboxylase to coproporphyrinogen I and then oxidized to coproporphyrin I. None of these will be degraded by heme oxidase. 

The genes for all the enzymes of human heme biosynthesis have been characterized (Table 32-2), and the structures of 5-aminolevulinic acid dehydratase (ALAD), hydroxymethyl-bilane synthase (HMBS), uroporphyrinogen-III synthase (UROS), uroporphyrinogen decarboxylase (UROD), and ferrochelatase (FECH) have been determined by x-ray crys-tallography. - - ... 

A splendid illustration of the use of 500 MHz NMR is provided by the water suppressed time course of porphyrin biosynthesis where porphobilinogen (PEG), the substrate for uro gens I and m and Vitamin 3 2 is transformed into the apparent product uro gen I which turns out to be a chemical artifact. Thus, during incubation of PEG with the enzyme, PEG deaminase ([D] Fig. 1 Mj. 33,000) the product released from the enzyme is pre-uro gen, or hydroxymethyl bilane (HME), whose characteristic spectrum (Fig. 1) (t 2 = 180 sec/30 C) can be seen transiently when the reaction is carried out at 4 C [12a,b]. The NMR method also uniquely defines HME as the substrate for the second enzyme, uro gen ni cosynthetase. In the absence of the latter enzyme, the cyclization of the head-to-tail tetrapyrrole HME takes place spontaneously. The deep-seated intra-molecular rearrangement of HME to uro gen El can now be studied by this technique. 

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