Biosynthesis of endogenous cardiac glycosides by …

Using a computational mlncRNA identification pipeline, we identified 2660 D. purpurea mlncRNA candidates, of which only about 12% can be grouped into families with at least two members in a family, while the others are single gene family members. Furthermore, the conservation of mlncRNAs is very low. Searching the NONCODE database of known npcRNAs, we found that only about 0.3% of the mlncRNAs analyzed was conserved, suggesting the vast majority of D. purpurea mlncRNAs are species-specific. These results are consistent with those obtained from other plant species including M. truncatula, Arabidopsis, wheat, and animals such as Drosophila and mouse [, , , , ], indicating mlncRNAs may be evolved with a low degree of constraint and many of them are probably undergoing frequent birth and death. It is particularly true for the mlncRNAs which produce non-conserved microRNA families represented by single genes [].

Biosynthesis of Endogenous Cardiac Glycosides by …

T1 - Steroid biosynthesis and renal excretion in human essential hypertension

Cardiac glycosides biosynthesis - …

N2 - The human circulation contains four readily distinguishable biologically active inhibitors of the sodium pump that appear to be endogenous to mammals. Of these, one has been purified to homogeneity and by numerous chromatographic, mass spectral, biochemical, and physiological analyses has been shown to be a novel steroidal isomer of ouabain in which the location and orientation of two or more steroidal hydroxyl groups differ. The human endogenous 'ouabain' (EO) is a high affinity reversible inhibitor of the pump with inotropic and vasopressor activity. Circulating levels of EO depend upon the adrenal cortex and metabolic events preceding and following pregnenolone formation are involved in EO biosynthesis. Within the adrenal gland, the stimulus-secretion mechanisms for EO secretion are distinct from those for aldosterone highlighting different regulation. Among Caucasians with essential hypertension, 30-45% have elevated circulating levels of EO. Sustained elevation of plasma ouabain in rats induces chronic hypertension with characteristics similar to those in patients and whose severity is determined by inherited factors and renal function. In conclusion, at least one of the mammalian counterparts to the cardiac glycosides is a novel steroidal isomer of ouabain. The isomer is secreted by the adrenal cortex, and augments cardiovascular function. The observation of this entity in the human circulation, the demonstration of its biosynthesis, and the existence of specific receptors suggest to us that EO is a novel adrenocortical hormone and may be part of a broader family of novel mammalian steroids that regulate the sodium pump and other processes.

Biosynthesis of cardiac glycosides: Nucleotide-bound …

AB - Science has long recognized the ubiquitously occurring deoxysugars as a novel and important class of carbohydrate, by virtue of the variety of potent and intriguing biological activities they exhibit. The study of the biosynthesis of these naturally vital molecules at a molecular level has received a great deal of attention in recent years, whether it be the well-established study of deoxyribonucleotide biosynthesis via ribonucleotide reductase or newer areas that include 3,6-dideoxyhexose construction and O antigen variation, as well as the emerging scrutiny of the biosynthesis of deoxysugar ligands of antibiotics and cardiac glycosides. This review attempts to update the various classes of deoxy, dideoxy, trideoxy, branched-chain, and amino sugars with respect to our current knowledge regarding the vast biological activities, genetics of formation, and molecular basis of their biosynthesis. In particular, the primary focus utilizes CDP-ascarylose biosynthesis, currently the best genetically and biochemically characterized dideoxysugar system, as a basis for comparison and postulation. This review helps display the elegant complexities of these essential natural saccharides and speculates upon tomorrow's potential applications.

is down-regulated by cardiac glycoside drugs digoxin ..
The early steps in the biosynthesis of steroids of both plants and animals are ..


The inhibitors of prostaglandin biosynthesis and nitric oxide production have been considered as potential anti-inflammatory and cancer chemopreventive agents.

a putative key enzyme involved in the biosynthesis of cardiac glycosides.

Steroidal glycosides or cardiac glycosides

Glycosides: Glycosides are found in virtually every and have vast therapeutic efficacy and, certain cases, toxic effect depending on the plant of origin and the dose of plant product ingested. They are glycosylated bioactive principles in which the aglycone moieties are constituted of the alkaloids, vitamins, polyphenols, steroids, terpenoids or antibiotics etc. bound to a mono- or oligosaccharide or to uronic acid (). Glycobiology has revealed that the glycosidic residue is crucial for bioactivity; in other circumstances, glycosylation improves pharmacokinetic parameters and may serve as leads to the development of new and more active drugs, as typified by the recently developed antibiotics-vancomycin (). A precise overview of physiologic role of glycosyl residue in bioactive principles as well as the structure/activity relationship has been described (). The most encountered glycosides of medicinal and toxicological importance are the vitamins glycosides, polyphenolic glycosides (anthraquinone glycosides), alkaloid glycosides, glycosides in the group of antibiotics (streptomycin), glycopeptides, cardiac glycosides, steroid and terpenoid glycosides, cyanogenic glycosides etc. (; ; ; ; ; ).

Aspirin and other NSAIDs exert their primary therapeutic by interfering with the biosynthesis of.

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Through high-throughput 454 sequencing and subsequent assembly, we obtained 23532 genes, of which 15626 encode conserved proteins. We determined 140 unigenes to be candidates involved in cardiac glycoside biosynthesis. It could be grouped into 30 families, of which 29 were identified for the first time in D. purpurea. We identified 2660 mRNA-like npcRNA (mlncRNA) candidates, an emerging class of regulators, using a computational mlncRNA identification pipeline and 13 microRNA-producing unigenes based on sequence conservation and hairpin structure-forming capability. Twenty five protein-coding unigenes were predicted to be targets of these microRNAs. Among the mlncRNA candidates, only 320 could be grouped into 140 families with at least two members in a family. The majority of D. purpurea mlncRNAs were species-specific and many of them showed tissue-specific expression and responded to cold and dehydration stresses. We identified 417 protein-coding genes with regions significantly homologous or complementary to 375 mlncRNAs. It includes five genes involved in secondary metabolism. A positive correlation was found in gene expression between protein-coding genes and the homologous mlncRNAs in response to cold and dehydration stresses, while the correlation was negative when protein-coding genes and mlncRNAs were complementary to each other.