Serendipity reveals the function and physiological role of a large family of proteins.

2021 ◽  
Author(s):  
Diana Downs
Keyword(s):  
Metabolic Pathways ◽  
Physiological Role ◽  
Large Family ◽  
Microbial Metabolism ◽  
Endonuclease Activity ◽  
Fundamental Information ◽  
Original Question

Microbial metabolism involves a complex set of interactions between metabolic pathways that include proteins of both known and uncharacterized function. While investigating the physiological strategy used by actinomycetes with two RpoB paralogs, Damiano et al uncovered the endonuclease activity of a member of the Rid family. While this finding was peripheral to the original question posed by the authors, it has considerable significance. The study by Damiano et al highlights how unexpected, but fundamental, information can be gained by following phenotypic leads.

scholarly journals New Evidence of Similarity between Human and Plant Steroid Metabolism: 5α-Reductase Activity in Solanum malacoxylon

Endocrinology ◽  
2003 ◽  
Vol 144 (1) ◽  
pp. 220-229 ◽  
Author(s):  
Fabiana Rosati ◽  
Giovanna Danza ◽  
Antonio Guarna ◽  
Nicoletta Cini ◽  
Milvia Luisa Racchi ◽  
...  
Keyword(s):  
Steroid Hormones ◽  
Metabolic Pathways ◽  
Reductase Activity ◽  
Physiological Role ◽  
Mechanisms Of Action ◽  
Plant Tissues ◽  
Solanum Malacoxylon ◽  
New Evidence ◽  
Mammalian System

Abstract The physiological role of steroid hormones in humans is well known, and the metabolic pathway and mechanisms of action are almost completely elucidated. The role of plant steroid hormones, brassinosteroids, is less known, but an increasing amount of data on brassinosteroid biosynthesis is showing unexpected similarities between human and plant steroid metabolic pathways. Here we focus our attention on the enzyme 5α-reductase (5αR) for which a plant ortholog of the mammalian system, DET2, was recently described in Arabidopsis thaliana. We demonstrate that campestenone, the natural substrate of DET2, is reduced to 5α-campestanone by both human 5αR isozymes but with different affinities. Solanum malacoxylon, which is a calcinogenic plant very active in the biosynthesis of vitamin D-like molecules and sterols, was used to study 5αR activity. Leaves and calli were chosen as examples of differentiated and undifferentiated tissues, respectively. Two separate 5αR activities were found in calli and leaves of Solanum using campestenone as substrate. The use of progesterone allowed the detection of both activities in calli. Support for the existence of two 5αR isozymes in S. malacoxylon was provided by the differential actions of inhibitors of the human 5αR in calli and leaves. The evidence for the presence of two isozymes in different plant tissues extends the analogies between plant and mammalian steroid metabolic pathways.

scholarly journals The physiological role of nucleobindin-2/nesfatin-1 and their potential clinical significance

2018 ◽  
Vol 72 ◽  
pp. 1084-1096
Author(s):  
Anna Skorupska ◽  
Andrzej Ożyhar ◽  
Dominika Bystranowska
Keyword(s):  
Cancer Cells ◽  
Metabolic Pathways ◽  
Physiological Role ◽  
Melanocortin System ◽  
Adrenocortical Cancer ◽  
Potential Biomarker ◽  
Treatment Of Obesity ◽  
High Level ◽  
Anorexigenic Effect

Nucleobindin-2 is a multidomain protein. Nucleobindin-2 can be cleaved into three peptide products: nesfatin-1, nesfatin-2 and nesfatin-3. It has been also shown that both Nucleobindin-2 and nesfatin-1 exhibit anorexigenic effect in rodents. In this review, we focused on a systematic characteristic of Nucleobindin-2, its anorexigenic effect and discussed possible mechanisms of its action. The first one is associated with melanocortin system and is leptin independent. The second – involves neurons that produce orexigenic neuropeptide Y. This has allowed integrating key findings which have important implications for treatment of obesity. We also presented Nucleobindin-2/nesfatin-1 as proteins which might become potentially important for understanding and treatment of such diseases as epilepsy, acute appendicitis or cancer. It has been shown that the Nucleobindin-2 function in cancerogenesis may be dual. The high level of Nucleobindin-2 and nesfatin-1 expression was found in colony, breast and endometrium cancer cells. Additionally, Nucleobindin-2/nesfatin-1 induced the proliferation process of these cells. In the future, Nucleobindin-2/nesfatin-1 may be used as a potential biomarker in diagnosis. However, Nucleobindin-2/nesfatin-1 inhibited ovarian and adrenocortical cancer cells proliferation and stimulated its apoptosis. The action of both proteins involved variety of metabolic pathways. The knowledge about activity control of Nucleobindin- 2/nesfatin-1 may contribute to new breakthrough in medicine.

The role of vitamin A and its pro-vitamin carotenoids in fetal and neonatal programming: gaps in knowledge and metabolic pathways

2020 ◽  
Vol 79 (1) ◽  
pp. 76-87
Author(s):  
Leonardo M de Souza Mesquita ◽  
Laís V Mennitti ◽  
Veridiana V de Rosso ◽  
Luciana P Pisani
Keyword(s):  
Vitamin A ◽  
Nutritional Status ◽  
Metabolic Pathways ◽  
Metabolic Diseases ◽  
Biological Effects ◽  
Physiological Role ◽  
Current Data ◽  
Cellular Processes ◽  
Pregnancy And Lactation

Abstract Vitamin A (VA) and its pro-vitamin carotenoids are naturally occurring lipophilic compounds involved in several cellular processes and metabolic pathways. Despite their broad spectrum of activities in the general population, dietary deficiencies of these compounds can potentially affect pregnancy outcomes. Since maternal nutritional status and diet composition during pregnancy and lactation can have long-lasting effects in offspring until adulthood, this study presents an overview of VA and the role of pro-VA carotenoids during pregnancy and lactation – the nutrition, metabolism, and biological effects in the offspring. The review aimed to discuss the pro-VA carotenoids and VA-associated pathways and summarize the results with reference to gestational disorders, and VA and pro-VA carotenoids as preventive agents. Also, considering that obesity, overweight, and metabolic diseases are major public health concerns worldwide, fetal and neonatal development is discussed, highlighting the physiological role of these molecules in obesity prevention. This review comprehensively summarizes the current data and shows the potential impact of these compounds on nutritional status in pregnancy and lactation.

scholarly journals Physiological Role of Acyl Coenzyme A Synthetase Homologs in Lipid Metabolism in Neurospora crassa

2013 ◽  
Vol 12 (9) ◽  
pp. 1244-1257 ◽  
Author(s):  
Christine M. Roche ◽  
Harvey W. Blanch ◽  
Douglas S. Clark ◽  
N. Louise Glass
Keyword(s):  
Neurospora Crassa ◽  
Metabolic Pathways ◽  
Lipid Membrane ◽  
Coenzyme A ◽  
De Novo ◽  
Physiological Role ◽  
Functional Redundancy ◽  
Content Type ◽  
Acyl Coenzyme A

ABSTRACTAcyl coenzyme A (CoA) synthetase (ACS) enzymes catalyze the activation of free fatty acids (FAs) to CoA esters by a two-step thioesterification reaction. Activated FAs participate in a variety of anabolic and catabolic lipid metabolic pathways, includingde novocomplex lipid biosynthesis, FA β-oxidation, and lipid membrane remodeling. Analysis of the genome sequence of the filamentous fungusNeurospora crassaidentified seven putative fatty ACSs (ACS-1 through ACS-7). ACS-3 was found to be the major activator for exogenous FAs for anabolic lipid metabolic pathways, and consistent with this finding, ACS-3 localized to the endoplasmic reticulum, plasma membrane, and septa. Double-mutant analyses confirmed partial functional redundancy of ACS-2 and ACS-3. ACS-5 was determined to function in siderophore biosynthesis, indicating alternative functions for ACS enzymes in addition to fatty acid metabolism. TheN. crassaACSs involved in activation of FAs for catabolism were not specifically defined, presumably due to functional redundancy of several of ACSs for catabolism of exogenous FAs.

Physiological Role of Cyclic Electron Flow in Higher Plants

2012 ◽  
Vol 30 (1) ◽  
pp. 100
Author(s):  
Wei HUANG ◽  
Shi-Bao ZHANG ◽  
Kun-Fang CAO
Keyword(s):  
Higher Plants ◽  
Electron Flow ◽  
Physiological Role ◽  
Cyclic Electron Flow

The Renal Outer Medullary Potassium Channel (ROMK): An Intriguing Pharmacological Target for an Innovative Class of Diuretic Drugs

2018 ◽  
Vol 25 (23) ◽  
pp. 2627-2636 ◽  
Author(s):  
Vincenzo Calderone ◽  
Alma Martelli ◽  
Eugenia Piragine ◽  
Valentina Citi ◽  
Lara Testai ◽  
...  
Keyword(s):  
Physiological Role ◽  
Clinical Use ◽  
Diuretic Activity ◽  
First Line ◽  
Potassium Homeostasis ◽  
Diuretic Drugs ◽  
Pharmacological Target ◽  
Diuretic Agents ◽  
Effective Drugs

In the last four decades, the several classes of diuretics, currently available for clinical use, have been the first line option for the therapy of widespread cardiovascular and non-cardiovascular diseases. Diuretic drugs generally exhibit an overall favourable risk/benefit balance. However, they are not devoid of side effects. In particular, all the classes of diuretics cause alteration of potassium homeostasis. <p> In recent years, understanding of the physiological role of the renal outer medullary potassium (ROMK) channels, has shown an intriguing pharmacological target for developing an innovative class of diuretic agents: the ROMK inhibitors. This novel class is expected to promote diuretic activity comparable to (or even higher than) that provided by the most effective drugs used in clinics (such as furosemide), with limited effects on potassium homeostasis. <p> In this review, the physio-pharmacological roles of ROMK channels in the renal function are reported, along with the most representative molecules which have been currently developed as ROMK inhibitors.

MicroRNAs as Biomarker for Breast Cancer

2020 ◽  
Vol 20 (10) ◽  
pp. 1597-1610 ◽  
Author(s):  
Taru Aggarwal ◽  
Ridhima Wadhwa ◽  
Riya Gupta ◽  
Keshav Raj Paudel ◽  
Trudi Collet ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Association Studies ◽  
Large Family ◽  
Breast Cancer Diagnosis ◽  
Cell Multiplication ◽  
Cell Physiology ◽  
Gene Transcript ◽  
Genome Wide Association Studies ◽  
Non Coding Rnas

Regardless of advances in detection and treatment, breast cancer affects about 1.5 million women all over the world. Since the last decade, genome-wide association studies (GWAS) have been extensively conducted for breast cancer to define the role of miRNA as a tool for diagnosis, prognosis and therapeutics. MicroRNAs are small, non-coding RNAs that are associated with the regulation of key cellular processes such as cell multiplication, differentiation, and death. They cause a disturbance in the cell physiology by interfering directly with the translation and stability of a targeted gene transcript. MicroRNAs (miRNAs) constitute a large family of non-coding RNAs, which regulate target gene expression and protein levels that affect several human diseases and are suggested as the novel markers or therapeutic targets, including breast cancer. MicroRNA (miRNA) alterations are not only associated with metastasis, tumor genesis but also used as biomarkers for breast cancer diagnosis or prognosis. These are explained in detail in the following review. This review will also provide an impetus to study the role of microRNAs in breast cancer.

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