Department of Biochemistry, Peoples' Friendship University, Moscow, Russia.
Laboratory of Combined Treatment, N.N. Blokhin Cancer Research Center, Moscow, Russia.
Amino Acids. 2021 Jan;53(1):111-118. doi: 10.1007/s00726-020-02930-4. Epub 2021 Jan 4.
L-lysine α-oxidase (LO) is an L-amino acid oxidase with antitumor, antimicrobial and antiviral properties. Pharmacokinetic (PK) studies were carried out by measuring LO concentration in plasma and tissue samples by enzyme immunoassay. L-lysine concentration in samples was measured spectrophotometrically using LO. After single i.v. injection of 1.0, 1.5, 3.0 mg/kg the circulating T of enzyme in mice varied from 51 to 74 min and the AUC values were 6.54 ± 0.46, 8.66 ± 0.59, 9.47 ± 1.45 μg/ml × h, respectively. LO was distributed in tissues and determined within 48 h after administration with maximal accumulation in liver and heart tissues. Mean time to reach the maximum concentration was highest for the liver-9 h, kidney-1 h and 15 min for the tissues of heart, spleen and brain. T of LO in tissues ranged from 7.75 ± 0.73 to 26.10 ± 2.60 h. In mice, plasma L-lysine decreased by 79% 15 min after LO administration in dose 1.6 mg/kg. The serum L-lysine levels remained very low from 1 to 9 h (< 25 μM, 17%), indicating an acute lack of L-lysine in animals for at least 9 h. Concentration of L-lysine in serum restored only 24 h after LO administration. The results of LO PK study show that it might be considered as a promising enzyme for further investigation as a potential anticancer agent.
L-赖氨酸α-氧化酶（LO）是一种具有抗肿瘤、抗菌和抗病毒特性的 L-氨基酸氧化酶。通过酶免疫测定法测量血浆和组织样品中的 LO 浓度进行药代动力学（PK）研究。使用 LO 通过分光光度法测量样品中的 L-赖氨酸浓度。在小鼠单次静脉注射 1.0、1.5、3.0 mg/kg 后，酶的循环 T 在 51 到 74 分钟之间变化，AUC 值分别为 6.54±0.46、8.66±0.59、9.47±1.45μg/ml×h。LO 分布在组织中，并在给药后 48 小时内测定，在肝脏和心脏组织中积累最多。达到最大浓度的平均时间对于肝脏为 9 小时，肾脏为 1 小时，心脏、脾脏和大脑组织为 15 分钟。LO 在组织中的 T 从 7.75±0.73 到 26.10±2.60 小时不等。在小鼠中，在给予 1.6mg/kg 的 LO 后 15 分钟，血浆 L-赖氨酸减少了 79%。在 1 至 9 小时期间，血清 L-赖氨酸水平非常低（<25μM，17%），表明动物体内至少在 9 小时内 L-赖氨酸严重缺乏。仅在 LO 给药后 24 小时血清 L-赖氨酸浓度才恢复。LO PK 研究的结果表明，它可能被认为是一种很有前途的酶，可进一步研究作为潜在的抗癌剂。
