FURTHER STUDIES ON THE METABOLISM OF UROCANIC-α-C14 ACID

1956 ◽  
Vol 34 (4) ◽  
pp. 783-790 ◽  
Author(s):  
M. Kraml ◽  
L. P. Bouthillier

The existence of radioactive metabolites in the liver extracts of rats a short time after injection of urocanic-α-C14 acid has been investigated. Glutamic acid, N-formiminoglutamic acid, and an unknown compound that yields glutamic acid on hydrolysis were the major urocanic acid catabolites found therein. These three substances accounted for as much as 75% of the total radiocarbon in the extracts. The sole catabolic pathway of importance for urocanic acid, in the rat, is the formation of glutamic acid. Since formylglutamic acid could not be detected in these extracts, the role of this substance as an obligatory urocanic acid catabolite becomes questionable.

1956 ◽  
Vol 34 (1) ◽  
pp. 783-790 ◽  
Author(s):  
M. Kraml ◽  
L. P. Bouthillier

The existence of radioactive metabolites in the liver extracts of rats a short time after injection of urocanic-α-C14 acid has been investigated. Glutamic acid, N-formiminoglutamic acid, and an unknown compound that yields glutamic acid on hydrolysis were the major urocanic acid catabolites found therein. These three substances accounted for as much as 75% of the total radiocarbon in the extracts. The sole catabolic pathway of importance for urocanic acid, in the rat, is the formation of glutamic acid. Since formylglutamic acid could not be detected in these extracts, the role of this substance as an obligatory urocanic acid catabolite becomes questionable.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yafei Wang ◽  
Erik Brodin ◽  
Kenichiro Nishii ◽  
Hermann B. Frieboes ◽  
Shannon M. Mumenthaler ◽  
...  

AbstractColorectal cancer and other cancers often metastasize to the liver in later stages of the disease, contributing significantly to patient death. While the biomechanical properties of the liver parenchyma (normal liver tissue) are known to affect tumor cell behavior in primary and metastatic tumors, the role of these properties in driving or inhibiting metastatic inception remains poorly understood, as are the longer-term multicellular dynamics. This study adopts a multi-model approach to study the dynamics of tumor-parenchyma biomechanical interactions during metastatic seeding and growth. We employ a detailed poroviscoelastic model of a liver lobule to study how micrometastases disrupt flow and pressure on short time scales. Results from short-time simulations in detailed single hepatic lobules motivate constitutive relations and biological hypotheses for a minimal agent-based model of metastatic growth in centimeter-scale tissue over months-long time scales. After a parameter space investigation, we find that the balance of basic tumor-parenchyma biomechanical interactions on shorter time scales (adhesion, repulsion, and elastic tissue deformation over minutes) and longer time scales (plastic tissue relaxation over hours) can explain a broad range of behaviors of micrometastases, without the need for complex molecular-scale signaling. These interactions may arrest the growth of micrometastases in a dormant state and prevent newly arriving cancer cells from establishing successful metastatic foci. Moreover, the simulations indicate ways in which dormant tumors could “reawaken” after changes in parenchymal tissue mechanical properties, as may arise during aging or following acute liver illness or injury. We conclude that the proposed modeling approach yields insight into the role of tumor-parenchyma biomechanics in promoting liver metastatic growth, and advances the longer term goal of identifying conditions to clinically arrest and reverse the course of late-stage cancer.


2021 ◽  
pp. 140349482110270
Author(s):  
Knut Ole Sundnes ◽  
Geir Sverre Braut

The COVID-19 epidemic has revealed a shortage of basic knowledge and understanding of pandemics, especially regarding their dynamics and how to contain them. The results are a host of governments’ decrees and instructions, one replacing the other, often within the same week. It has further, in a truly short time, resulted in an overwhelming number of publications, many of them prioritising early publication over quality. This commentary addresses the concept of structured research related to disasters and how the use of endorsed guidelines will facilitate well-designed evaluation research with improved rigour and external validity, even if applied retrospectively. The outcome should be a solidified knowledge base. Further, the important role of public health efforts is to be highlighted, as their role has proved crucial during the COVID-19 pandemic.


Author(s):  
Thamer Y. Mutter ◽  
Gerben J. Zylstra

Sphingomonas wittichii RW1 grows on the two related compounds dibenzofuran (DBF) and dibenzo- p -dioxin (DXN) as the sole source of carbon. Previous work by others (P.V. Bunz, R. Falchetto, and A.M. Cook. Biodegradation 4:171-8, 1993, doi: 10.1007/BF00695119) identified two upper pathway meta cleavage product hydrolases (DxnB1 and DxnB2) active on the DBF upper pathway metabolite 2-hydroxy-6-oxo-6-(2-hydroxyphenyl)-hexa-2,4-dienoate. We took a physiological approach to determine the role of these two enzymes in the degradation of DBF and DXN by RW1. Single knockouts of either plasmid located dbfB1 or chromosome located dbfB2 had no effect on RW1 growth on either DBF or DXN. However, a double knockout lost the ability to grow on DBF but still grew normally on DXN demonstrating that DbfB1 and DbfB2 are the only hydrolases involved in the DBF upper pathway. Using a transcriptomic-guided approach we identified a constitutively expressed third hydrolase encoded by the chromosomally located SWIT0910 gene. Knockout of SWIT0910 resulted in a strain that no longer grows on DXN but still grows normally on DBF. Thus the DbfB1 and DbfB2 hydrolases function in the DBF but not the DXN catabolic pathway and the SWIT0190 hydrolase functions in the DXN but not the DBF catabolic pathway. Importance S. wittichii RW1 is one of only a few strains known to grow on DXN as the sole course of carbon. Much of the work deciphering the related RW1 DXN and DBF catabolic pathways has involved genome gazing, transcriptomics, proteomics, heterologous expression, and enzyme purification and characterization. Very little research has utilized physiological techniques to precisely dissect the genes and enzymes involved in DBF and DXN degradation. Previous work by others identified and extensively characterized two RW1 upper pathway hydrolases. Our present work demonstrates that these two enzymes are involved in DBF but not DXN degradation. In addition, our work identified a third constitutively expressed hydrolase that is involved in DXN but not DBF degradation. Combined with our previous work, this means that the RW1 DXN upper pathway involves genes from three very different locations in the genome: an initial plasmid-encoded dioxygenase and a ring cleavage enzyme and hydrolase encoded on opposite sides of the chromosome.


1996 ◽  
Vol 67 (5) ◽  
pp. 423-429 ◽  
Author(s):  
Shinobu FUJIMURA ◽  
Hidenori KOGA ◽  
Hiromi TAKEDA ◽  
Naoko TONE ◽  
Motoni KADOWAKI ◽  
...  

2018 ◽  
Vol 85 (5) ◽  
Author(s):  
Ri-Qing Yu ◽  
Zohre Kurt ◽  
Fei He ◽  
Jim C. Spain

ABSTRACT Many plants produce allelopathic chemicals, such as stilbenes, to inhibit pathogenic fungi. The degradation of allelopathic compounds by bacteria associated with the plants would limit their effectiveness, but little is known about the extent of biodegradation or the bacteria involved. Screening of tissues and rhizosphere of peanut (Arachis hypogaea) plants revealed substantial enrichment of bacteria able to grow on resveratrol and pterostilbene, the most common stilbenes produced by the plants. Investigation of the catabolic pathway in Sphingobium sp. strain JS1018, isolated from the rhizosphere, indicated that the initial cleavage of pterostilbene was catalyzed by a carotenoid cleavage oxygenase (CCO), which led to the transient accumulation of 4-hydroxybenzaldehyde and 3,5-dimethoxybenzaldehyde. 4-Hydroxybenzaldehyde was subsequently used for the growth of the isolate, while 3,5-dimethoxybenzaldehyde was further converted to a dead-end metabolite with a molecular weight of 414 (C24H31O6). The gene that encodes the initial oxygenase was identified in the genome of strain JS1018, and its function was confirmed by heterologous expression in Escherichia coli. This study reveals the biodegradation pathway of pterostilbene by plant-associated bacteria. The prevalence of such bacteria in the rhizosphere and plant tissues suggests a potential role of bacterial interference in plant allelopathy. IMPORTANCE Pterostilbene, an analog of resveratrol, is a stilbene allelochemical produced by plants to inhibit microbial infection. As a potent antioxidant, pterostilbene acts more effectively than resveratrol as an antifungal agent. Bacterial degradation of this plant natural product would affect the allelopathic efficacy and fate of pterostilbene and thus its ecological role. This study explores the isolation and abundance of bacteria that degrade resveratrol and pterostilbene in peanut tissues and rhizosphere, the catabolic pathway for pterostilbene, and the molecular basis for the initial cleavage of pterostilbene. If plant allelopathy is an important process in agriculture and management of invasive plants, the ecological role of bacteria that degrade the allelopathic chemicals must be equally important.


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