ニワトリ肝より,リン酸マグネシウム存在下にアミドホスフォリボシルトランスフェラーゼを電気泳動的に均一に精製し,活性並びにプリンヌクレオチドによる阻害に対する感受性が安定な標品を得た.この標品はトリス緩衝液中では分子量約11万の二量体として存在しているが,基質PRPPによりさらに会合が進む.PRPPによって会合した酵素は阻害剤AMPにより再び解離する傾向を示す.この事実はニワトリ肝におけるプリンヌクレオチドの合成が,この酵素のもつアロステリックな性質によって調節されていることを示唆する.

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The effects of a high protein diet on purine metabolism in gouty and non-gouty chickens were compared. The daily urinary urate excretion were compared in gouty and non-gouty chickens fed a high protein (40%) and a normo protein (17%) diets. The daily urinary urate excretion in gouty chicken on high protein diet was more than that in non-gouty ones. The activities of six enzymes involved in purine metabolism (G-PRPP-AT, PRPP synthetase, glutamine synthetase, HGPRT, APRT and xanthine dehydrogenase) in the livers of gouty and non-gouty chickens on high and normo protein diets were also compared. The activities of G-PRPP-AT and glutamine synthetase in gouty chicken were more highly induced by a high protein diet than in non-gouty ones. In contrast, HGPRT and APRT activities in gouty chicken were decreased by a high protein diet while those in non-gouty ones were increased. A high protein diet induced PRPP synthetase and xanthine dehydrogenase in similar extent in gouty and nongouty chickens. The hepatic contents of PRPP, glutamine, oxypurine and urate were estimated. A high protein diet increased the hepatic PRPP content both in gouty and non-gouty chickens. On the other hand, the hepatic glutainine content in gouty chicken was decreased by a high protein diet, but not in non-gouty ones. Increase of urate content in the liver was observed only in gouty chicken, and it was twice in nongouty ones. These results suggest that the excessive supply of glutamine is one of the important factors in the accelerated purine and urate biosynthesis in gouty chicken.

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Purine代謝異常を伴う原発性免疫不全症には,T,B両リンパ球の機能低下を伴うADA欠損症とTリンパ球のみの機能低下を伴うPNP欠損症がある. 両酵素とも purine salvage 経路の酵素でありながら,発現する病型が異なる.この病型の差は,T,B両リンパ球間でのpurine代謝調節機構の差に原因して生ずるものと推測される.そこで我々はヒトT,B両リンパ球を用いて,生化学的方法および新たに開発した酵素組織化学的方法とにより,PNP活性を比較検討した.同時にADA活性も比較検討した.生化学的には,Tリンパ球の方がBリンパ球に比して,PNP活性が約3倍,ADA活性が約2倍有意に高いとの所見を得た.Formazan穎粒形成による酵素組織化学的方法でも,PNP染色およびADA染色ともに,T リンパ球の方がB リンパ球に比して顆粒が多数であった. しかし, T , B 両リンパ球聞の顆粒形成の差はPNP染色でより大であった.これらの結果は,Tリンパ球機能にPNPがより重要な役割を果していることを示唆する.リンパ球による尿酸産生には, T リンパ球がより多くの寄与をし,PNP,ADA活性の低いBリンパ球の寄与は少ないと推測される.

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In 22 patients with hyperuricemia, measurements of the CH₅₀, the proteins of complement-system, proteinase inhibitors, plasminogen and fibrinogen in the blood were carried out, in order to find out pathophysiological response into sodium urate deposition. Significant increase of C₄, C₃, C₃-Activator and fibrinogen was generally present in patients with hyperuricemia as compared to normal control. In patients with previous history of gouty attack, these changes became more prominent and CH₅₀ and C_1q also showed significant increase. The documentation of these finding which were obtained in non-acute phase, suggests us the presence of more or less pathophysiological changes in the background of hyperuricemic patients. And study of these complement activity and proteins in the blood might be significant procedures to support diagnosis ot so-called asymptomatic nyperuricemia.

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Uric acid is the end-product of purine metabolism, and the purines are nitrogenous bases derived from the breakdown of nucleic acids. It was presented by the authors at the Eighteenth Annual Meeting of the Japanese Society of Neurology in Nagoya, May 18,1977, that CSF uric acid levels were increased in patients with histologically malignant brain tumor. Responsible factors for increased CSF uric acid levels are thought to be (1) increased permeability of blood-CSF barrier; (2) cerebral cell necrosis; and (3) increased turnover of the nucleic acid. The purpose of this paper is to find out the diagnostic value of CSF uric acid levels in patients with brain tumor compared with CSF lactate dehydrogenase activities. CSF uric acid levels and lactate dehydrogenase activities were investigated in 30 cases of normal control and in 52 cases of brain tumor. The mean values and standard deviations of CSF uric acid levels and lactate dehydrogenase activities were as follows in normal controls.Increased CSF uric acid levels and lactate dehydrogenase activities over the age of 50 are thought to be due to cerebral cell necrosis. Both CSF uric acid levels and lactate dehydrogenase activities were increased in histologically malignant brain tumors with numerous mitotic figures such as grade III-IV astrocytoma, medulloblastoma and sarcomatous meningioma. But, there is a strange phenomenon named “paradoxical normalization”. It is a phenomenon that both CSF uric acid levels and lactate dehydrogenase activities are normalized in histologically malignant brain tumors with cyst formation. CSF uric acid levels were not influenced by increased intracranial pressure. But CSF lactate dehydrogenase activities were more easily influenced and increased in almost all cases above 400 mm H₂O, even if these cases were histologically benign. Uric acid levels and lactate dehydrogenase activities were investigated in the cyst fluids of brain tumor. Both of them were more concentrated in the cyst fluid than in the CSF. In the malignant brain tumor, uric acid levels and lactate dehydrogenase activities in the cyst fluids were higher than the serum levels. But in the benign brain tumor, they were lower than the serum levels.

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In the presence of Cu²⁺, ascorbate decomposes histamine in citrate phosphate buffer (pH 6.5). The breakdown is completely inhibited by catalase, but only slightly by superoxide dismutase, and scanvenger of OH. Addition of H₂O₂ to the reaction mixture markedly enhances the rate of histamine breakdown by ascorbate. However, H₂O₂ alone cannot breakdown histamine even in the presence of Cu²⁺. Therefore, it is concluded that the combination of H₂O₂ and monodehydroascorbic acid, both of which are produced during the autooxidation of ascorbate, plays a major role in the histamine transformation. Ascorbic acid cannot be replaced by equimolar concentration of uric acid, in the system of histamine breakdown, while the latter, along with other purine derivatives, blocked ascorbate-induced histamine transformation. Detailed mechanisms in respect to the inhibitory effect of urate on ascorbate-induced histamine breakdown are now in progress in our laboratory.

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