Taylor Adam M, Kammath Vishnu, Bleakley Aaron
Lancaster Medical School, Faculty of Health & Medicine, Lancaster University, Lancaster, Bailrigg LA1 4YW, United Kingdom.
Lancaster Medical School, Faculty of Health & Medicine, Lancaster University, Lancaster, Bailrigg LA1 4YW, United Kingdom.
Med Hypotheses. 2016 Jun;91:77-80. doi: 10.1016/j.mehy.2016.04.001. Epub 2016 Apr 8.
The hypothesis that is proposed is that tyrosinase, an enzyme widely found within the human body is implicated in the ochronosis that occurs in alkaptonuria; an autosomal recessive condition first used by Archibald Garrod to describe the theory of "Inborn Errors of Metabolism." The disease results from the absence of a single enzyme in the liver that breaks down homogentisic acid; this molecule becomes systemically elevated in sufferers. The condition is characterised by a clinical triad of symptoms; homogentisic aciduria from birth, ochronosis (darkening) of collagenous tissues (from ∼30years of age) and ochronotic osteoarthropathy in weight bearing joints due to long term ochronosis in them (from ∼40years of age). Tyrosinase, a polyphenol oxidase has been shown in many species to contribute to the darkening of tissues in many organisms; including humans in the production of melanin. Tyrosinase under the right conditions shows alterations in its substrate specificity and may contribute to the darkening seen in AKU where it moves away from polymerising tyrosine but also homogentisic acid, the causative molecule in alkaptonuria, that is present in excess.
提出的假说是，酪氨酸酶（一种在人体内广泛存在的酶）与黑尿症中出现的褐黄病有关；黑尿症是一种常染色体隐性疾病，阿奇博尔德·加罗德最早用它来描述“先天性代谢缺陷”理论。这种疾病是由于肝脏中一种分解尿黑酸的单一酶缺失所致；这种分子在患者体内会系统性升高。该病的特征是一组三联征症状；出生时即有尿黑酸尿症，胶原组织褐黄病（约30岁开始），以及由于负重关节长期出现褐黄病（约40岁开始）而导致的褐黄病性骨关节炎。酪氨酸酶是一种多酚氧化酶，在许多物种中已表明它会导致许多生物体组织变黑；包括人类在黑色素生成过程中。在合适的条件下，酪氨酸酶的底物特异性会发生改变，可能会导致黑尿症中出现的组织变黑，此时它不再聚合酪氨酸，而是聚合尿黑酸（黑尿症中的致病分子，在体内过量存在）。
