在小鼠中已经报道了不同组织的精氨酸血浆浓度和精氨酸酶活性的性别差异。此外,雄性而非雌性C57BL/6小鼠具有生长所需的饮食精氨酸。
这项研究的目的是检验精氨酸酶II是精氨酸代谢的性二态性的关键因素的假设。
年轻成年男性和女性野生型(WT),C57BL/6背景小鼠上的杂合子和精氨酸酶II敲除小鼠输注标记的瓜氨酸,精氨酸鸟氨酸,苯丙氨酸,和酪氨酸来确定这些氨基酸的出现和相互转化的速率。在肝脏中测量组织精氨酸酶活性,心,空肠,肾,胰腺,和带有精氨酸放射性同位素的脾脏。基因型的影响,性别,他们的互动得到了测试。
雌性小鼠比雄性同窝小鼠多生产36%的瓜氨酸,转化为更大的精氨酸内源性合成,通量,和血浆浓度(42、6和27%,分别;P<0.001)。雌性小鼠的苯丙氨酸通量(10%)也更大,表明整个蛋白质分解的速率更高;然而,他们的蛋白质合成率低于男性(18%;P<0.001)。精氨酸酶II的消融减少了雌性瓜氨酸的产生和精氨酸的从头合成,并增加了雄性小鼠中精氨酸的出现率和血浆精氨酸浓度(16%和22%,分别;P<0.001)。精氨酸酶II缺失没有影响,然而,观察到全身蛋白质动力学。精氨酸酶II活性存在于胰腺中,肾,空肠,和脾脏;WT女性的肾精氨酸酶活性比WT女性高2倍。
精氨酸的内源性合成及其处置存在明显的性二态性。雌性小鼠的精氨酸利用率高于雄性同窝小鼠。精氨酸酶II的消融增加了雄性小鼠中精氨酸的可用性。
Sex differences in plasma concentration of arginine and arginase activity of different tissues have been reported in mice. In addition, male but not female C57BL/6 mice have a dietary arginine requirement for growth.
The goal of this research was to test the hypothesis that arginase II is a key factor in the sexual dimorphism of arginine metabolism.
Young adult male and female wild type (WT), and heterozygous and arginase II knockout mice on a C57BL/6 background mice were infused with labeled citrulline, arginine, ornithine, phenylalanine, and tyrosine to determine the rates of appearance and interconversion of these amino acids. Tissue arginase activity was measured in the liver, heart, jejunum, kidney, pancreas, and spleen with an arginine radioisotope. The effect of genotype, sex, and their interaction was tested.
Female mice produced ∼36% more citrulline than their male littermates, which translated into a greater arginine endogenous synthesis, flux, and plasma concentration (42, 6, and 27%, respectively; P < 0.001). Female mice also had a greater phenylalanine flux (10%) indicating a greater rate of whole protein breakdown; however, they had a lower protein synthesis rate than males (18%; P < 0.001). The ablation of arginase II reduced the production of citrulline and the de novo synthesis of arginine in females and increased the rate of appearance of arginine and plasma arginine concentration in male mice (16 and 22%, respectively; P < 0.001). No effect of arginase II deletion, however, was observed for whole-body protein kinetics. Arginase II activity was present in the pancreas, kidney, jejunum, and spleen; WT females had a ∼2-fold greater renal arginase activity than their WT counterparts.
A clear sexual dimorphism exists in the endogenous synthesis of arginine and its disposal. Female mice have a greater arginine availability than their male littermates. The ablation of arginase II increases arginine availability in male mice.