Hpd, also known as 4-hydroxyphenylpyruvate dioxygenase, is a critical enzyme in tyrosine metabolism [1,2]. Tyrosine metabolism pathways are essential for various biological processes, and the proper function of Hpd is crucial for maintaining normal physiological states [1,2].

In breast cancer, Hpd overexpression is positively correlated with histological grade and clinical stage, and inversely correlated with 10-year overall survival rates, suggesting it may be a prognostic predictor and potential therapeutic target [1]. Also, decreased Hpd expression, a cause of human tyrosinemia, is regulated by the TTC36-STK33-PELI1 signaling axis. Ttc36-/-mice have reduced Hpd expression in the liver, exhibit tyrosinemia, damage to hippocampal neurons, and deficits of learning and memory, revealing the significance of this regulatory axis in tyrosinemia and associated neurological disorders [2].

In conclusion, Hpd is vital for tyrosine metabolism. The study of Hpd through animal models, like the Ttc36-/-mice, has provided insights into its role in diseases such as breast cancer and tyrosinemia-related neurological damage, highlighting its potential as a biomarker and therapeutic target in these disease areas [1,2].

References:

1. Wang, Xuanyu, Shang, Yongjun, Yang, Lina, Shan, Changliang, Liu, Shuangping. 2019. HPD overexpression predicts poor prognosis in breast cancer. In Pathology, research and practice, 215, 152524. doi:10.1016/j.prp.2019.152524. https://pubmed.ncbi.nlm.nih.gov/31277952/

2. Xie, Yajun, Lv, Xiaoyan, Ni, Dongsheng, Lu, Zhimin, Zhou, Qin. 2019. HPD degradation regulated by the TTC36-STK33-PELI1 signaling axis induces tyrosinemia and neurological damage. In Nature communications, 10, 4266. doi:10.1038/s41467-019-12011-0. https://pubmed.ncbi.nlm.nih.gov/31537781/