Tryptophan analogues and the mechanism of induction of rat-liver tryptophan pyrrolase, in vivo

TY - JOUR

T1 - Tryptophan analogues and the mechanism of induction of rat-liver tryptophan pyrrolase, in vivo

AU - Greengard, Olga

N1 - Funding Information: mechanism basically different from that involved in substrate induction~, ~a. To avoid complications arising from stress-induced adrenocortical secretion, adrenalectomized rats were employed in the present experiments. It may be seen in Fig. I that the effect of (~-methyltryptophan in vivo is similar to that of tryptophan: the initial change, occurring during the first hour after its administration, is a conversion of apo-to holotryt)tophan pyrrolase and the next stage, as seen at 4 h, is a more than 3-fold increase in total tryptophan pyrr~lase levels. Fig. I also shows that 5-methyltryptophan which does not raise the total enzynle level does not influence the holo-to apotryptophan pyrrolase ratio. Similar results were obtained with acetyl-~.-tryt)tophan. The level of tryptophan t)yrrolase reaches a maximum 4 h after L-tryptophan administration. Subsequently the holo-to apotrypt~@~an pyrmlase rat% and then the total amount of tryt)tophan pyrrolase decreases rapidly to normal levels '~. In contrast, SOURI(I,;S ANI) TOWNSEND 2 showed that after t~-mettlyltryptophalx a(Iminis-tration the total enzynle level remains high for 3 days. For this to occur, the afore-menti(med hypothesis requires the holo to apotryptot)han pyrrolase rati(~ to remain high for a \])rolonged period. Assays carried out 53 h after ~-methyltryt)tophal~ treatment show that this is the case (@ lrig. I). The apparent affinity of t~em~ t~) apotryptophan pyrrolase increases ~ith increasing concentrations of tryptophan s, and this phenomenon appears t~ m~derlie the tryptophan-mediated c{mversion ~,f at)o to hoh}tryptophan l)yrr~}las{' i~ vivo ~. The present observations suggest that ~-naethyltryptophan, though not a substrate, has a similar effect, whereas 5-methyltryptoI)han, which may 1)e a substrate:k does not influence the h()h)-t~) apotryptophan pyrrolase rati(). Thus, this study fl~rther sut>t)orts the hypothesis on the lleCcssary role of the heine coenzyme in the "sub.strate"-induced elevation ¢~l the amount of liw~ tryptopha~ l)yrrolase and suggests that the effectiveness of tryptophan analogues as inducers is related to their ability to raise the holo-to at)otryptophan pyrrolase ratio. This work was supported by the Muscular Dystrophy Associations of America and by U.S. Pul)lic Health Service grant CA-o7o37-oz. I am indet)ted to Merck, Sharpe and Dohme l,al)oratories for gifts of t~-methyltryptophan and to M. A. SmTH for capal)le technical assistance.

PY - 1964/6/1

Y1 - 1964/6/1

UR - http://www.scopus.com/inward/record.url?scp=50549212206&partnerID=8YFLogxK

U2 - 10.1016/0926-6569(64)90315-3

DO - 10.1016/0926-6569(64)90315-3

M3 - Article

AN - SCOPUS:50549212206

SN - 0926-6569

VL - 85

SP - 492

EP - 494

JO - BBA - Enzymological Subjects

JF - BBA - Enzymological Subjects

IS - 3

ER -