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Effects of Drugs
Published in Stephen W. Carmichael, Susan L. Stoddard, The Adrenal Medulla 1986 - 1988, 2017
Stephen W. Carmichael, Susan L. Stoddard
Ekker, Sourkes and Gabor (1988) used immunotitration to examine the changes in S-adenosylmethionine decarboxylase content after administration of piribedil or 2-deoxyglucose. They determined that there was no difference in the half-life of the decarboxylase activity in adrenal glands of untreated rats and of rats receiving piribedil. These and other experiments suggested that the decrease in adrenal S-adenosylmethionine decarboxylase activity and protein content caused by stress is due to a decrease in the rate of synthesis of the enzyme.
Eflornithine
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Following the success of eflornithine as a treatment for HAT, the potential activity of eflornithine in other parasitic diseases, including malaria, has been investigated. Polyamine metabolism in Plasmodia is more complex than in mammalian cells, and as a rapidly proliferating organism, malaria parasites are dependent on an abundant supply of polyamines (Muller et al., 2008). In plasmodia, the two key enzymes, S-adenosylmethionine decarboxylase and ornithine decarboxylase, are arranged on a bifunctional protein (Muller et al., 2008). Although eflornithine was shown to not have any useful activity as an antimalarial, other inhibitors of polyamine metabolism are the subjects of ongoing research (Muller et al., 2008).
Role of Polyamines in Prolactin Actions
Published in James A. Rillema, Actions of Prolactin on Molecular Processes, 1987
Polyamine biosynthesis in eukaryotic cells involves several precursors such as arginine, ornithine, methionine, and S-adenosylmethionine (Figure 2). Ornithine is mainly formed in the urea cycle through the cleavage of urea from arginine by arginase. Ornithine is then converted to putrescine in a reaction catalyzed by ornithine decarboxylase (ODC).29–31S-Adenosylmethionine is a universal methyl donor in transmethylation reactions. In polyamine biosynthesis, this compound is first decarboxylated by S-adenosylmethionine decarboxylase (S-ado-met DC).29–31S-Ado-met serves as the propylamine donor in the formation of spermidine from putrescine by spermidine synthase as well as in the formation of spermine from spermidine by spermine synthase.29–31
Emerging compounds and therapeutic strategies to treat infections from Trypanosoma brucei: an overhaul of the last 5-years patents
Published in Expert Opinion on Therapeutic Patents, 2023
Francesco Melfi, Simone Carradori, Cristina Campestre, Entela Haloci, Alessandra Ammazzalorso, Rossella Grande, Ilaria D’Agostino
Pentamidine (Figure 1) is an aromatic diamidine used since the 1930s. The rationale for using diamidines was based on their hypoglycemic effect and the intent to starve the trypanosomes of their source of nutrients. Moreover, the diamidines are known to act with a trypanocidal effect, whose mechanism of action has been widely studied, and several proposals were made. It seems that pentamidine can bind to T. brucei DNA double helix at adenine-thymine-rich regions in the minor groove, forming cross-linkages between two adenines, preferentially four to five base pairs apart. Moreover, pentamidine is a reversible inhibitor of trypanosomal S-adenosylmethionine decarboxylase (SAMDC), impairing the mechanism of polyamines synthesis [4]. Likewise, other modes of action are kinetoplast fragmentation and inhibition of the biosynthetic pathways for proteins and phospholipids [5].
Effect of Methionine on AMD1 Gene Expression in Prostate Cancer Cells
Published in Nutrition and Cancer, 2021
Shaochen Shen, Linhong Zeng, Hongwei Huang
MET plays a vital role in the formation of S-adenosyl-L-methionine (SAM). SAM is central in the biological methyl-group donor and the source of aminopropyl groups in polyamine biosynthesis. Increased tRNA methylase activity has been found in several experimental and human tumors. In addition, an increase in the polyamine biosynthesis is associated with the neoplastic state (5–7). S-adenosylmethionine decarboxylase 1 (AMD1), also known as SAMDC, is the rate-limiting enzyme regulating polyamine metabolism. SAM is decarboxylated by AMD1. Decarboxylated SAM (dcSAM) is important in the formation of polyamines (8, 9). The role of MET in prostate cancer and its specific mechanism has been scarcely studied. In this study, prostate cancer cells were cultured In Vitro to analyze whether the abnormal expression of AMD1 gene promotes MET in prostate cancer. We further explored the methionine mechanism in promoting the occurrence and development of prostate cancer.
The latest automated docking technologies for novel drug discovery
Published in Expert Opinion on Drug Discovery, 2021
An interesting strategy named SCAR (steric-clashes alleviating receptor) that performs covalent docking without covalent-bond formation was recently reported by Ai et al. [186]. In SCAR, the reactive residue side chain in the binding site of the protein is mutated to glycine, and docking of covalent ligands are performed in this site by using a noncovalent docking protocol. Authors used SCAR to perform a high-throughput screening and found covalent inhibitors of S-adenosylmethionine decarboxylase with novel molecular scaffolds. They also demonstrated that the method is applicable to other covalent-docking examples by test it with a dataset containing 76 covalent complexes, and observed that their results are comparable to the ones shown by other covalent docking programs.