Mock Donald M, Mock Nell I
Department of Biochemistry, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
J Nutr. 2002 Jul;132(7):1945-50. doi: 10.1093/jn/132.7.1945.
Recent clinical studies have provided evidence that marginal biotin deficiency is more common than previously thought. The validity of that conclusion rests on two indicators of biotin status that depend on renal function. Our goal was to develop and assess the usefulness of two additional indicators in detecting marginal biotin status in a rat model, i.e., 1) activity of the biotin-dependent enzyme propionyl-CoA carboxylase in lymphocytes; and 2) urinary excretion of 3-hydroxypropionic acid, an organic acid that reflects decreased activity of propionyl-CoA carboxylase. Marginal-to-moderate biotin deficiency was induced experimentally by an egg-white diet (deficient rats); the biotin-supplemented rats were fed the egg-white diet plus supplemental biotin. Propionyl-CoA carboxylase activity was determined by an optimized H(14)CO(3)(-) incorporation assay. Urinary organic acids were determined by gas chromatography/mass spectrometry. Lymphocyte propionyl-CoA carboxylase activity decreased dramatically and in parallel with hepatic propionyl-CoA carboxylase activity. By d 7, lymphocyte propionyl-CoA carboxylase activity in each rat in the deficient group had decreased to less than the lowest value of any rat on d 0. By two-way ANOVA, the effects of diet (P < 0.0001), time (P < 0.005) and their interaction (P < 0.0001) were all significant. The urinary excretion of 3-hydroxypropionic acid did not differ between the two groups. Lymphocyte propionyl-CoA carboxylase activity is an early and sensitive indicator of marginal biotin deficiency, whereas the urinary excretion of 3-hydroxypropionic acid is not.
近期的临床研究已提供证据表明，边缘性生物素缺乏比之前认为的更为常见。该结论的有效性基于两个取决于肾功能的生物素状态指标。我们的目标是开发并评估另外两个指标在大鼠模型中检测边缘性生物素状态的有用性，即：1）淋巴细胞中生物素依赖性酶丙酰辅酶A羧化酶的活性；2）3-羟基丙酸的尿排泄量，3-羟基丙酸是一种反映丙酰辅酶A羧化酶活性降低的有机酸。通过给予蛋清饮食（缺乏生物素的大鼠）实验性诱导边缘性至中度生物素缺乏；补充生物素的大鼠喂食蛋清饮食加补充生物素。通过优化的H(14)CO(3)(-)掺入试验测定丙酰辅酶A羧化酶活性。通过气相色谱/质谱法测定尿有机酸。淋巴细胞丙酰辅酶A羧化酶活性显著下降，且与肝脏丙酰辅酶A羧化酶活性平行下降。到第7天，缺乏组每只大鼠的淋巴细胞丙酰辅酶A羧化酶活性已降至低于第0天任何大鼠的最低值。通过双向方差分析，饮食（P < 0.0001）、时间（P < 0.005）及其相互作用（P < 0.0001）的影响均具有显著性。两组之间3-羟基丙酸的尿排泄量没有差异。淋巴细胞丙酰辅酶A羧化酶活性是边缘性生物素缺乏的早期敏感指标，而3-羟基丙酸的尿排泄量则不是。
