ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Phenylacetate is not excreted to any significant extent as the free acid in rat urine, but must be metabolized in the liver and kidney, first to phenylacetyl-CoA, then to phenylacetylglycine. One hour after [14C]phenylacetate loading, the radioactivity in the liver and kidneys of the young rat could all be accounted for as unchanged phenylacetate (50-5573, phenylacetylglycine (35–40%), and phenylacetyl-CoA (5–8%). In the brain, the radioactivity was present mainly as phenylacetate (82–90%); only 10–18% was found as phenylacetyl-CoA. The formation of phenylacetyl-CoA appeared to be the rate limiting step in the clearance of phenylacetate.In the urine at least 95% of the radioactivity was present as phenylacetylglycine, less than 1% as phenylacetate, and 3–4% as phenylacetyl-CoA. The concentration of phenylacetylglycine in the urine was therefore used as a measure of the in vivo rate of phenylacetatc clearance. This detoxication process was found to develop postnatally. The formation of phenylacetylglycine was barely detecrabie in the newborn rat and remained relatively slow for about 2 weeks. During the third week a large increase in enzymatic activity, approx 40% occurred. Adult level of activity was reached in the 40 day old rat.The extremely slow rate of detoxication in the newborn animal was reflected in the persistence of high concentrations of phenylacetate in the tissues. The relevance of our findings to human phenyl-ketonuria is discussed
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1471-4159.1979.tb02282.x
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