Tetrahydropteridines, also

PT Pertussis toxin PTCA Percutaneous transluminal coronary angioplasty PTCR Percutaneous transluminal coronary recanalization Pte-H Tetrahydropteridine PUFA Polyunsaturated fatty acid PUMP-1 Punctuated metalloproteinase also known as matrilysin... 

Dopamine synthesis in dopaminergic terminals (Fig. 46-3) requires tyrosine hydroxylase (TH) which, in the presence of iron and tetrahydropteridine, oxidizes tyrosine to 3,4-dihydroxyphenylalanine (levodopa.l-DOPA). Levodopa is decarboxylated to dopamine by aromatic amino acid decarboxylase (AADC), an enzyme which requires pyri-doxyl phosphate as a coenzyme (see also in Ch. 12). 

This iron-dependent enzyme [EC 1.14.16.6], also known as L-mandelate 4-hydroxylase, catalyzes the reaction of (5)-2-hydroxy-2-phenylacetate with tetrahydropteridine and dioxygen to produce (5)-4-hydroxymandelate, dihy-dropteridine, and water. 

As a final example of regioselective control (Scheme 25), sulfonium ylides usually give nitrones when reacted with nitroso groups via oxaziridine intermediates. However, 7-aryl-2-dimethylamino-3,4,5,6-tetrahydropteridine-4,6-diones 120 were directly formed when nitrosopyrimidine 121 reacted with dimethylphenacylsulfonium bromides 122 instead of the isomeric 5-oxides <1996H(43)437>. It was also reported that the resulting pteridines were reduced to give 7,8-dihydro derivatives 123 with sodium dithionite (Table 7). 

Pteridine also adds ammonia at low temperature to form 4-amino-3,4-dihydropteridine (42) which is transformed in a slower reaction into 6,7-diamino-5,6,7,8-tetrahydropteridine (43) (Scheme 5). 2-Chloropteridine (36) shows the same behavior, whereas 2-chloro-4-phenylpteridine (37) and 2-methylthiopteridine (38) lead directly to the corresponding 6,7-diamino-5,6,7,8-tetrahydro derivatives (43) (Scheme 5). The 4-amino-3,4-dihydropteridines can easily be oxidized to the 4-aminopteridines <75RTC45>. Covalent hydrations with various 6,7-bis-trifluoromethyl-pteridine derivatives were studied showing that 6,7-bis-trifluoromethylpteridine (40) itself and the cor-... 

The enzyme has been purified from rat and human livers. The properties of the human enzyme are essentially similar to those of the rat enzyme [204, 205]. Phenylalanine hydroxylase has also been purified from rat kidney. Available methods of investigation suggest that the kidney enzyme is similar to that of liver [206]. The human liver enzyme exists in a soluble and particulate form. The particulate and soluble enzymes have identical pH optima and K s apparent for phenylalanine and 2-amino-4-hydroxy-6,7-dimethyl-5,6,7,8-tetrahydropteridine [207]. 

In experiments employing dimethyltetrahydropteridine in stoichiometric amounts, it was observed that both enzyme II and TPNH were no longer required for the hydroxylation. The reaction leads not only to the formation of tyrosine, but also to the oxidation of the tetrahydro-pteridine to a compound rapidly converted to a dihydropteridine. Addition of enzyme II and TPNH enables the tetrahydropteridine to function catalytically. The TPNH can also be replaced, in the absence of enzyme... 

Because the tetrahydropteridine behaved catalytically in the presence of TPNH, it was also clear that there was an intermediate between the active tetrahydropteridine and the inactive 7,8-dihydropteridine and that this intermediate was capable of being reduced back to the tetra-... 

This kind of mechanism also has the advantage of providing an explanation for the inactivity of the natural cofactor in the defluorination reaction without discarding the idea that its mode of action is essentially the same as that of the synthetic tetrahydropteridines. According... 

The factor in glucose dehydrogenase preparations which can stimulate tyrosine formation can be replaced by crystalline catalase when tetrahydropteridines are used while catalase cannot replace glucose dehydrogenase with the cofactor. It is possible that the glucose dehydrogenase fractions contain another factor, besides catalase, which is required for the activity of the cofactor. This additional factor may also be involved in the conversion of the cofactor to an active form. 

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