scholarly journals Halogenated tryptophan derivatives disrupt essential transamination mechanisms in bloodstream form Trypanosoma brucei

2020 ◽  
Vol 14 (12) ◽  
pp. e0008928
Author(s):  
Peter E. Cockram ◽  
Emily A. Dickie ◽  
Michael P. Barrett ◽  
Terry K. Smith

Amino acid metabolism within Trypanosoma brucei, the causative agent of human African trypanosomiasis, is critical for parasite survival and virulence. Of these metabolic processes, the transamination of aromatic amino acids is one of the most important. In this study, a series of halogenated tryptophan analogues were investigated for their anti-parasitic potency. Several of these analogues showed significant trypanocidal activity. Metabolomics analysis of compound-treated parasites revealed key differences occurring within aromatic amino acid metabolism, particularly within the widely reported and essential transamination processes of this parasite.

1994 ◽  
Vol 267 (5) ◽  
pp. E672-E679 ◽  
Author(s):  
L. J. Wykes ◽  
J. D. House ◽  
R. O. Ball ◽  
P. B. Pencharz

Low tyrosine solubility in total parenteral nutrition (TPN) solutions complicates meeting the aromatic amino acid needs of infants. This study compared the effectiveness of two tyrosine precursors to supply the aromatic amino acid needs of TPN-fed neonatal piglets with a control group in which total aromatic acid needs were met by the addition of phenylalanine (Phe). Eighteen 3-day-old male Yorkshire piglets (6/group) received TPN for 8 days by central line. The solution was supplemented with Phe or one of the following two tyrosine precursors: N-acetyltyrosine (N-AcTyr) or glycyltyrosine (GlyTyr). Aromatic amino acid metabolism, growth, and nitrogen utilization were measured. Average amino acid and energy intakes were 14.6 g.kg-1.day-1 and 1,050 kJ.kg-1.day-1. Nitrogen balance and utilization were significantly higher (P < 0.05) in piglets in the control Phe group and on the GlyTyr regimen. The high urinary excretion of N-AcTyr (65%) confirms its low bioavailability. Flux and oxidation were significantly higher (P < 0.05) in the Phe group. High plasma Phe levels and excretion of Phe catabolites, as well as the high plasma tyrosine in the GlyTyr group, indicate that current strategies employed to meet the aromatic amino acid needs of neonates on TPN need further refinement.


2017 ◽  
Vol 284 (1854) ◽  
pp. 20162607 ◽  
Author(s):  
Marcos Sterkel ◽  
Pedro L. Oliveira

The phenylalanine/tyrosine degradation pathway is frequently described as a catabolic pathway that funnels aromatic amino acids into citric acid cycle intermediates. Previously, we demonstrated that the accumulation of tyrosine generated during the hydrolysis of blood meal proteins in Rhodnius prolixus is potentially toxic, a harmful outcome that is prevented by the action of the first two enzymes in the tyrosine degradation pathway. In this work, we further evaluated the relevance of all other enzymes involved in phenylalanine/tyrosine metabolism in the physiology of this insect. The knockdown of most of these enzymes produced a wide spectrum of distinct phenotypes associated with reproduction, development and nymph survival, demonstrating a highly pleiotropic role of tyrosine metabolism. The phenotypes obtained for two of these enzymes, homogentisate dioxygenase and fumarylacetoacetase, have never before been described in any arthropod. To our knowledge, this report is the first comprehensive gene-silencing analysis of an amino acid metabolism pathway in insects. Amino acid metabolism is exceptionally important in haematophagous arthropods due to their particular feeding behaviour.


1999 ◽  
Vol 181 (2) ◽  
pp. 689-694 ◽  
Author(s):  
Kyeong R. Park ◽  
Jean-Christophe Giard ◽  
Juno H. Eom ◽  
Shawn Bearson ◽  
John W. Foster

ABSTRACT Two acid-inducible genes, aniC and aciK, that require anaerobiosis and tyrosine for expression were identified as orf326a encoding a potential amino acid/polyamine antiporter and hyaB encoding hydrogenase I, respectively. Cyclic AMP (cAMP) receptor protein, cAMP, and TyrR, regulator of aromatic amino acid metabolism, were strong positive regulators of both genes.


2007 ◽  
Vol 137 (6) ◽  
pp. 1579S-1585S ◽  
Author(s):  
Cornelis H. C. Dejong ◽  
Marcel C. G. van de Poll ◽  
Peter B. Soeters ◽  
Rajiv Jalan ◽  
Steven W. M. Olde Damink

1986 ◽  
Vol 14 (6) ◽  
pp. 999-1001 ◽  
Author(s):  
CHRISTOPHER I. POGSON ◽  
MARK SALTER ◽  
RICHARD G. KNOWLES

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