In this letter to biochemist Henry Lardy, Kornberg shared his recent work on the pathway of uridine triphosphate synthesis,
part of the early work that led him to nucleotide synthesis, and ultimately to DNA synthesis.
Number of Image Pages:
2 (115,498 Bytes)
1951-02-06 (February 6, 1951)
Lardy, Henry A.
University of Wisconsin
Original Repository: Stanford University Libraries. Department of Special Collections and University Archives. Arthur Kornberg Papers
Reproduced with permission of Arthur Kornberg.
Medical Subject Headings (MeSH):
From Physician to Enzyme Hunter, 1942-1953
February 6, 1951
I was happy to get your letter and especially the information that you may have isolated uridine triphosphate from muscle.
I remember very well the data which Kuby showed me when I was in Madison, but, as you point out, the impression at that time
was that you might be dealing with adenosine tetraphosphate. In view of the lower absorption coefficient of uridine and cytidine,
this must have been a mixture containing some adenosine polyphosphate as well.
The history of our interest in UTP goes like this: When Leloir's work came out, I wondered whether UTP might be a condensing
agent like ATP forming a pyrophosphate bridge with glucose-1-phosphate. Recently Ted Park (at Camp Detrick) was kind enough
to send me some uridine diphosphate isolated from his Staph. aureus compound. We observed that in a system containing phosphopyruvate
and a rather purified transferring enzyme from rabbit muscle, there was a quantitative conversion to uridine triphosphate.
We did some preliminary work with UTP and glucose-1-phosphate in yeast extracts, but the results are too uncertain to be relied
upon. At the moment our chief concern is to get adequate amounts of uridine diphosphate for further work. We have had very
poor luck with yeast as a source material, the yields being far lower than anticipated from Leloir's report. We are just
about to try to prepare it from Staph. Aureus according to Park and Johnson's method.
Since the enzymatic synthesis of UTP was carried out in a rather purified system and we have not had the problem of separating
it from adenine compounds, I probably cannot be of much help on your separation problem. I might suggest this, however: In
some other work we were doing recently, we attained very handsome chromatograms of ATP on Dowex-1 chloride using .01 N HCl
in .05 M NaCl as the eluting agent. Also, it is my impression that the ability of mercuric salts to precipitate ATP in acid
solution is related to the amino group, and this might prove to be a means of separation.
I am planning to present this work at the ACS meetings in Boston in April, and I wonder whether you will be attending these
sessions. In any case, I will try to keep you informed of our progress in this work, and will, in turn, be very grateful
for information about what you folks are finding out.