Reminiscence of 40-year research on nitrogen metabolism.
Bottom Line: These amino acids are not efficiently metabolized in the liver, so I had to consider the physiology of extrahepatic tissues as well.Finally, I came across a huge protease complex, the proteasome.Whether these players, small amino acid metabolizing enzymes and the huge protease complex, danced well in harmony on my playground or not, I still do not know.
Affiliation: Tokushima University, Japan.
This article summarizes my research over 40 years. The main theme of my work is nitrogen metabolism of amino acids, though later I focused on protein turnover in the cell. In the first years of my research work, I was busy dissecting the pathways involved in the metabolism of certain amino acids and their related enzymes. Then I became interested in the physiology and regulation of matabolism of these amino acids. For that, I used primary cultured hepatocytes, which contain many liver-specific enzymes. However, this play field was very rough around 1970 and hence I had to smooth them (differentiated) first. We discovered a specific growth factor (hepatocyte growth factor, HGF) in rat platelets. Exceptionally, I also worked on branched chain amino acids (valine, leucine and isoleucine). These amino acids are not efficiently metabolized in the liver, so I had to consider the physiology of extrahepatic tissues as well. Finally, I came across a huge protease complex, the proteasome. Whether these players, small amino acid metabolizing enzymes and the huge protease complex, danced well in harmony on my playground or not, I still do not know.
Mentions: In September 1957, I returned to Osaka and was appointed a Research Assistant at the Department of Nutrition, School of Medicine, with Dr. Suda, who had been at that time promoted to a Professor. Again, I was lucky for being able to secure a position as soon as I returned to Japan. I say this because I know of the suffering of young graduates nowadays in finding new posts. After coming back to Japan, the Japanese Society of Biochemistry organized the International Symposium of Enzyme Chemistry in Tokyo and Kyoto, which represented the first international meeting of biochemistry in Japan. The symposium was attended by several famous scientists from around the world, who delivered excellent lectures followed by heated discussion and resulted in the publication of excellent papers.3) The symposium program also included several satellite meetings including amino acid metabolism (Photo. 1). Interestingly, the symposium provided the chance for young Japanese biochemists to obtain work abroad.