High incidence up to 70% of gout was found in inbred chickens of Fayoumi strain fed a 40% protein diet. Mean plasma uric acid levels of gouty and non-gouty male chickens of Fayoumi. strain and white Leghorn. strain fed a 40% protein diet, were 21.5,8.5,5.0 mg/dl, respectively. Disappearance curves of plasma uric acid after intravenous injection of [U-¹⁴C]uric acid in both non-gouty and gouty chickens were parallel, although uric acid pool size was much larger in gouty chickens than in non-gouty ones. Next, urine was collected through cloaca after the fecal outlet was artificially made at the abdominal wall. Urinary [¹⁴C] uric acid was much more in gouty chickens compared with non-gouty chickens, after [U-¹⁴C]glycine was intravenously injected. These findings showed that the. cause of hyperuricemia of gouty chickens was the accelerated uric acid synthesis rather than the impared urinary excretion of uric acid. Activities of hepatic enzymes such as hypoxanthine-guanine-phosphoribosyltransferase, PPRP synthetase, PPRP amidotransferase, glutaminase, glutamine synthetase, etc. were compared between non-gouty and gouty chickens. Feed back inhibition of hepatic amidotransferase by IMP, GNP or AMP was observed in a smaller extent in gouty chickens than in nongouty ones. This chicken will be used as an animal model of at least a type of human gout.

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Vol. 1 (1977) No. 1 p. 30

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Vol. 1 (1977) No. 1 p. 60

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Vol. 1 (1977) No. 1 p. 79

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Vol. 1 (1977) No. 1 p. 142

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¹⁴C-Allopurinol(100mg/Kg,i.p.)投与後のマウス尿中に排泄される放射性Allopurinol及びOxipurinol含量には著明な性差がみとめられた. しかしながら,14C-Oxipurinol投与後のマウスの尿中放射性Oxipurinol量には雌雄差はみとめられなかった. 成熟マウス肝上清分画のAllopurinol酸化酵素活性ならびにAldehyde oxidase活性(基質NMN)には雌雄差がみとめられたがXanthine oxidase活性(基質Hypoxanthjne)には有意な性差は観察されなかった. 性腺摘除マウス肝Allopurinol酸化酵素活性及びAldehyde oxidase活性はTestosterone投与により上昇したが,Estradiol-17βによっては影響を受けなかった. 絶食により,Allopurinol酸化酵素活性及びAldehyde oxidase活性は同程度低下した. Xanthine oxidaseは凍結融解ならびにTris-HCl Buffer( KClを含む)での透析操作により,その活性は著しく上昇したが,Allopurinol酸化酵素活性ならびにAldehyde oxidase活性は共に変化しなかったが,透析液中からKClを除くと両酵素活性共に低下することが見い出された. また,この条件で低下した両酵素はK⁺,NH₄⁺,Rb⁺の添加で活性化された. Aldehyde oxidase精製時,Allopurinol酸化酵素活性ならびにAldehyde oxidase活性は同じ比率で上昇した. Allopurinol及びNMN酸化反応は,それぞれNMN及びAllopurinolにより競合的に抑制された. 多くの生体活性アミンならびにその関連物質は両酵素活性を同程度抑制した.
以上の知見より, マウス肝上清に存在するAll-opurinol酸化酵素はXanthine oxidaseであるよりはむしろAldehyde oxidaseであることが示された.

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Measurement was made of HGPRT and APRT activities in erythrocytes for 15 cases of Lesch-Nyhan syndrome. As for the activity of HGPRT in 2 cases with Lesch-Nyhan syndrome, there appeared the enzyme activity when the substrates, concentrations of hypoxanthine and PRPP, were made to rise. The activity of HGPRT in erythrocytes of two cases at high concentration of hy poxanthine rose in a sigmoid curve when the concentration of PRPP was made to rise, whereupon the apparent Km stood at 9.2×10^-3 and 9.8×10^-3. This apparent Km was about 30 times that of the control group. The Km to hypoxanthine was 1.8×10^-4 in both cases, which was about 10 times that of the control group. The activity of HGPRT in erythrocytes of other 13 cases showed no change.
In 1970, Seegmiller et al. provided deficiency of HGPRT activity in erythrocytes of patients with Lesch-Nyhan syndrome (1).
In 1971, Arnold et al. (2) and Rubin et al. (3) purified HGPRT enzyme protein in erythrocytes of normal adult males and prepared anti-HGPRT serum using rats or rabbits. It was made clear that HGPRT enzyme protein is present in erythrocytes of patients with Lesch-Nyhan syndrome since these erythrocytes al beit without enzyme activity, showed an absorption band to anti-HGPRT serum serum immunologically. HGPRT protein in erythrocytes of patients with Lesch-Nyhan syndrome was reported to be 140μg/ml erythrocytes, an amount equal to that in normal adult males (4,5).
Recently, McDonald et al. (6) have reported a variant type of erythrocyte HGPRT enzyme in one case of Lesch-Nyhan syndrome. This is of great interest since there have been previous reports merely on cases in which the enzyme activity was defect in this syndrome.
We have made measurement of erythrocytes HGPRT and APRT enzyme activities in 15 cases of Lesch-Nyhan syndrome. In two cases, a rise in HGPRT activity was demonstrated for variations in concentrations of hypoxanthine and PRPP, the substrates.
In this paper mention will be made of the enzymatic study on erythrocytes HGPRT and APRT activities referring to these two cases.

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For estimation of uric acid metabolism of hyperuricemia in patients with gout, uric acid clearance and urinary excretion of urate were determined in 150 cases of gout and 10 normal controls. Mean and standard deviation of the clearance and the urinary excretion of the controls were 9.4 ±1.6 ml/min and 0.52 ±0.10 mg/kg/hr, respectively. Therefore, cases with uric acid clearance under 6.1 ml/min were defined as underexcretion type, those under 3.9 ml/min were as severe underexcretion type. Regarding the urinary excretion of urate, cases with the excerion over 0.73mg/kg/hr should be defined as overproduction type. However, because ratio of urinary excretion to synthesis of urate in patient with gout were generally lower than those of the controls and 90%of patients who had urinary excretion over 0.50 mg/kg/hr were overproduction type in the urate-14C turnover study as reported previously, we assumed that those with urinary excretion over 0.50 mg/kg/hr were overproduction type. By the criteria,150cases of hyperuricemia were classified into 6 groups, that is, overproduction type, overproduction with moderate underexcretion type, overproduction with severe underexcretion type, moderate underexcretion type, severe underexcretion type and normal production and excretion type, which were 29 cases (19.3%),23cases (15.3%) 1 case (0.7%),38 cases (25.3%) 57 cases (38.0%) and 2 cases (1.4%) respectively.
Serum uric acid level of overproduction type was generally lower than that of underexcretion type but urinary excretion, uric acid clearance, creatinine clearance and clearance ratio of overproduction type were generally higher than those of underexcretion type.
Significant positive correlation were demons t r ated between uric acid clearance and urinary excretion (r=0.77), uric acid clearance and clearance ratio (r=0.66), uric acid clearance and creatinine clearance (r=0.40), creatinine clearance and urinary excretion (r=0.28), and significant negative correlation were obtained between serum uric acid level and uric acid clearance (r=-0.54), creatinine clearance and clearance ratio (r=-0.34), serum uric acid level and clearance ratio (r=-0.29), serum uric acid level and creatinine clearance (r=-0.26), respectively.
To estimate production of uric acid in hyperuricemia of gout more precisely, modification of the clearance method was discussed.

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