Reversal of fungitoxicity of 8-quinolinols and their copper(II) bischelates. II. Reversal of the action of 8-quinolinol by DL-α-lipoic acid

1981 ◽  
Vol 27 (6) ◽  
pp. 612-615 ◽  
Author(s):  
Herman Gershon ◽  
Larry Shanks

The effect of amino acids and derivatives, Krebs cycle acids and related compounds, fatty acids, and vitamins and related compounds on the toxicity of 8-quinolinol and bis(8-quinolinolato)copper(II) to Aspergillus oryzae (ATCC 1011) was studied. Only aliphatic thiol-containing compounds (cysteine, glutathione, dithioerythritol, and dithiothreitol) and DL-α-lipoic acid protected against 8-quinolinol but not its copper(II) bischelate.It is suggested that 8-quinolinol inhibits lipoic acid biosynthesis, and the mode of fungitoxicity of 8-quinolinol is different from that of bis(8-quinolinolato)copper(II).

2008 ◽  
Vol 74 (16) ◽  
pp. 5078-5085 ◽  
Author(s):  
Aner Gurvitz ◽  
J. Kalervo Hiltunen ◽  
Alexander J. Kastaniotis

ABSTRACT We describe the physiological function of heterologously expressed Mycobacterium tuberculosis InhA during de novo lipoic acid synthesis in yeast (Saccharomyces cerevisiae) mitochondria. InhA, representing 2-trans-enoyl-acyl carrier protein reductase and the target for the front-line antituberculous drug isoniazid, is involved in the activity of dissociative type 2 fatty acid synthase (FASII) that extends associative type 1 fatty acid synthase (FASI)-derived C20 fatty acids to form C60-to-C90 mycolic acids. Mycolic acids are major constituents of the protective layer around the pathogen that contribute to virulence and resistance to certain antimicrobials. Unlike FASI, FASII is thought to be incapable of de novo biosynthesis of fatty acids. Here, the genes for InhA (Rv1484) and four similar proteins (Rv0927c, Rv3485c, Rv3530c, and Rv3559c) were expressed in S. cerevisiae etr1Δ cells lacking mitochondrial 2-trans-enoyl-thioester reductase activity. The phenotype of the yeast mutants includes the inability to produce sufficient levels of lipoic acid, form mitochondrial cytochromes, respire, or grow on nonfermentable carbon sources. Yeast etr1Δ cells expressing mitochondrial InhA were able to respire, grow on glycerol, and produce lipoic acid. Commensurate with a role in mitochondrial de novo fatty acid biosynthesis, InhA could accept in vivo much shorter acyl-thioesters (C4 to C8) than was previously thought (>C12). Moreover, InhA functioned in the absence of AcpM or protein-protein interactions with its native FASII partners KasA, KasB, FabD, and FabH. None of the four proteins similar to InhA complemented the yeast mutant phenotype. We discuss the implications of our findings with reference to lipoic acid synthesis in M. tuberculosis and the potential use of yeast FASII mutants for investigating the physiological function of drug-targeted pathogen enzymes involved in fatty acid biosynthesis.


1975 ◽  
Vol 21 (3) ◽  
pp. 409-411 ◽  
Author(s):  
Herman Gershon ◽  
Raulo Parmegiani ◽  
Janice Baricko Hauck

The effect of amino acids and related compounds on the toxicity of 8-quinolinols and their copper(II) bischelates to Aspergillus oryzae (ATCC 1011) was studied. None of the compounds tested except the thiol-containing compounds cysteine, cysteamine, glutathione, and N-acetylcysteine reversed the inhibitory action of 8-quinolinol but not that of 5-iodo-8-quinolinol or bis(8-quinolinolato)copper(II). It appears that the mechanism(s) of fungitoxicity of 8-quinolinol is different from that of 5-iodo-8-quinolinol or bis(8-quinolinolato)copper(II).


Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1010-P
Author(s):  
VICTORIA E. PARKER ◽  
DARREN ROBERTSON ◽  
TAO WANG ◽  
DAVID C. HORNIGOLD ◽  
MAXIMILIAN G. POSCH ◽  
...  

2020 ◽  
Vol 21 (8) ◽  
pp. 785-798 ◽  
Author(s):  
Abedin Abdallah ◽  
Evera Elemba ◽  
Qingzhen Zhong ◽  
Zewei Sun

The gastrointestinal tract (GIT) of humans and animals is host to a complex community of different microorganisms whose activities significantly influence host nutrition and health through enhanced metabolic capabilities, protection against pathogens, and regulation of the gastrointestinal development and immune system. New molecular technologies and concepts have revealed distinct interactions between the gut microbiota and dietary amino acids (AAs) especially in relation to AA metabolism and utilization in resident bacteria in the digestive tract, and these interactions may play significant roles in host nutrition and health as well as the efficiency of dietary AA supplementation. After the protein is digested and AAs and peptides are absorbed in the small intestine, significant levels of endogenous and exogenous nitrogenous compounds enter the large intestine through the ileocaecal junction. Once they move in the colonic lumen, these compounds are not markedly absorbed by the large intestinal mucosa, but undergo intense proteolysis by colonic microbiota leading to the release of peptides and AAs and result in the production of numerous bacterial metabolites such as ammonia, amines, short-chain fatty acids (SCFAs), branched-chain fatty acids (BCFAs), hydrogen sulfide, organic acids, and phenols. These metabolites influence various signaling pathways in epithelial cells, regulate the mucosal immune system in the host, and modulate gene expression of bacteria which results in the synthesis of enzymes associated with AA metabolism. This review aims to summarize the current literature relating to how the interactions between dietary amino acids and gut microbiota may promote host nutrition and health.


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