Jansen G A, Verhoeven N M, Denis S, Romeijn G, Jakobs C, ten Brink H J, Wanders R J
University of Amsterdam, Academic Medical Centre, Department of Pediatrics, Emma Children's Hospital, Laboratory for Genetic Metabolic Diseases (Room F0-224), P.O. Box 22700, 1100 DE, Amsterdam, Netherlands.
Biochim Biophys Acta. 1999 Sep 22;1440(2-3):176-82. doi: 10.1016/s1388-1981(99)00126-2.
Phytanic acid is broken down by alpha-oxidation in three steps finally yielding pristanic acid. The first step occurs in peroxisomes and is catalysed by phytanoyl-CoA hydroxylase. We have studied the second step in the alpha-oxidation pathway, which involves conversion of 2-hydroxyphytanoyl-CoA to pristanal catalysed by 2-hydroxyphytanoyl-CoA lyase. To this end, we have developed a stable isotope dilution gas chromatography-mass spectrometry assay allowing activity measurements in rat liver homogenates. Cell fractionation studies demonstrate that in rat liver 2-hydroxyphytanoyl-CoA lyase is localised in peroxisomes. This finding may have important implications for inherited diseases in man characterised by impaired phytanic acid alpha-oxidation.
植烷酸通过α-氧化分三步分解，最终生成降植烷酸。第一步发生在过氧化物酶体中，由植烷酰辅酶A羟化酶催化。我们研究了α-氧化途径的第二步，这一步涉及由2-羟基植烷酰辅酶A裂解酶催化将2-羟基植烷酰辅酶A转化为降植醛。为此，我们开发了一种稳定同位素稀释气相色谱-质谱分析法，可用于测量大鼠肝脏匀浆中的活性。细胞分级分离研究表明，在大鼠肝脏中，2-羟基植烷酰辅酶A裂解酶定位于过氧化物酶体。这一发现可能对以植烷酸α-氧化受损为特征的人类遗传性疾病具有重要意义。
