Hormone-Induced Lipolysis and The Metabolic Pathways Providing Energy To The Cell: A Possible Role of Atp As a Rate-Limiting Factor

1975 ◽  
pp. 105-122 ◽  
Author(s):  
G. Fassina ◽  
P. Dorigo ◽  
R. M. Gaion
Keyword(s):  
Metabolic Pathways ◽  
Limiting Factor ◽  
Rate Limiting

scholarly journals Glypican-1 drives unconventional secretion of Fibroblast Growth Factor 2

2021 ◽  
Author(s):  
Carola Sparn ◽  
Eleni Dimou ◽  
Annalena Meyer ◽  
Roberto Saleppico ◽  
Sabine Wegehingel ◽  
...  
Keyword(s):  
Growth Factor ◽  
Heparan Sulfate ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 2 ◽  
Structural Basis ◽  
Limiting Factor ◽  
Fibroblast Growth ◽  
Unconventional Secretion ◽  
Rate Limiting

Fibroblast Growth Factor 2 (FGF2) is a tumor cell survival factor that is transported into the extracellular space by an unconventional secretory mechanism. Cell surface heparan sulfate proteoglycans are known to play an essential role in this process. Unexpectedly, we found that among the diverse sub-classes consisting of syndecans, perlecans, glypicans and others, Glypican-1 (GPC1) is both the principle and rate-limiting factor that drives unconventional secretion of FGF2. By contrast, we demonstrate GPC1 to be dispensable for FGF2 signaling into cells. We provide first insights into the structural basis for GPC1-dependent FGF2 secretion, identifying disaccharides with N-linked sulfate groups to be enriched in the heparan sulfate chains of GPC1 to which FGF2 binds with high affinity. Our findings have broad implications for the role of GPC1 as a key molecule in tumor progression.

scholarly journals Ketogenesis Impact on Liver Metabolism Revealed by Proteomics of Lysine β-hydroxybutyrylation

2021 ◽  
Author(s):  
Kevin B. Koronowski ◽  
Carolina M. Greco ◽  
He Huang ◽  
Jin-Kwang Kim ◽  
Jennifer L. Fribourgh ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Ketone Bodies ◽  
Hepatic Metabolism ◽  
Mass Spectrometry Analysis ◽  
Metabolic Enzyme ◽  
Spectrometry Analysis ◽  
Evolutionarily Conserved ◽  
Specific Manner ◽  
Rate Limiting

SUMMARYKetone bodies are evolutionarily conserved metabolites that function as energy substrates, signaling molecules and epigenetic regulators. β-hydroxybutyrate (β-OHB) is utilized in lysine β-hydroxybutyrylation (Kbhb) of histones, which associates with starvation-responsive genes, effectively coupling ketogenic metabolism with gene expression. The emerging diversity of the lysine acylation landscape prompted us to investigate the full proteomic impact of Kbhb. Global protein Kbhb is induced in a tissue-specific manner by a variety of interventions that evoke β-OHB. Mass spectrometry analysis of the β-hydroxybutyrylome in mouse liver revealed 891 sites of Kbhb within 267 proteins enriched for fatty acid, amino acid, detoxification and 1-carbon metabolic pathways. Kbhb of S-adenosyl-L-homocysteine hydrolase (AHCY), a rate-limiting enzyme of the methionine cycle, results in inhibition of enzymatic activity. Our results illuminate the role of Kbhb on hepatic metabolism under ketogenic conditions and demonstrate the functional consequence of this modification on a central metabolic enzyme.

Why Do Children With Specific Language Impairment Name Pictures More Slowly Than Their Peers?

1996 ◽  
Vol 39 (5) ◽  
pp. 1081-1098 ◽  
Author(s):  
Margaret Lahey ◽  
Jan Edwards
Keyword(s):  
Language Impairment ◽  
Specific Language Impairment ◽  
Receptive Language ◽  
Limiting Factor ◽  
Language Performance ◽  
Specific Language ◽  
Language Problems ◽  
Different Types ◽  
Rate Limiting

To examine the role of different cognitive processes in accounting for the slower naming times of children with specific language impairment (SLI) relative to peers with no language impairment (NLI), three tasks designed to stress different types of processing were administered: naming pictures with the signal to respond presented at various delay intervals, naming following different durations of exposure to identical and unrelated primes, and vocally responding to nonlinguistic stimuli. Children with SLI, aged 4 to 9.5 years, were significantly slower than their NLI age peers on naming and on responding to nonlinguistic stimuli, but the effect of delay interval before naming and of duration of prime exposure before naming was similar for both groups. Results suggested that speed of naming is related to the slower nonlinguistic response processing of children with SLI and not to speed of their linguistic or perceptual processing. To examine differences in processing that might relate to pattern of language performance we examined responses of two subgroups of SLI. The subgroup of children whose language problems involved expressive but not receptive skills was not significantly slower than their NLI peers. The children whose problems involved both expressive and receptive language were significantly slower, but this was influenced by age. Findings are discussed in terms of language performance, age, task variables, and a generalized rate-limiting factor.

scholarly journals Activation of SAT1 engages polyamine metabolism with p53-mediated ferroptotic responses

2016 ◽  
Vol 113 (44) ◽  
pp. E6806-E6812 ◽  
Author(s):  
Yang Ou ◽  
Shang-Jui Wang ◽  
Dawei Li ◽  
Bo Chu ◽  
Wei Gu
Keyword(s):  
Cell Death ◽  
Metabolic Pathways ◽  
Cell Metabolism ◽  
Specific Inhibitor ◽  
Polyamine Metabolism ◽  
Cycle Arrest ◽  
Induced Stress ◽  
Rate Limiting ◽  
Insight Into

Although p53-mediated cell-cycle arrest, senescence, and apoptosis remain critical barriers to cancer development, the emerging role of p53 in cell metabolism, oxidative responses, and ferroptotic cell death has been a topic of great interest. Nevertheless, it is unclear how p53 orchestrates its activities in multiple metabolic pathways into tumor suppressive effects. Here, we identified the SAT1 (spermidine/spermine N1-acetyltransferase 1) gene as a transcription target of p53. SAT1 is a rate-limiting enzyme in polyamine catabolism critically involved in the conversion of spermidine and spermine back to putrescine. Surprisingly, we found that activation of SAT1 expression induces lipid peroxidation and sensitizes cells to undergo ferroptosis upon reactive oxygen species (ROS)-induced stress, which also leads to suppression of tumor growth in xenograft tumor models. Notably, SAT1 expression is down-regulated in human tumors, and CRISPR-cas9–mediated knockout of SAT1 expression partially abrogates p53-mediated ferroptosis. Moreover, SAT1 induction is correlated with the expression levels of arachidonate 15-lipoxygenase (ALOX15), and SAT1-induced ferroptosis is significantly abrogated in the presence of PD146176, a specific inhibitor of ALOX15. Thus, our findings uncover a metabolic target of p53 involved in ferroptotic cell death and provide insight into the regulation of polyamine metabolism and ferroptosis-mediated tumor suppression.

scholarly journals Role of fructose 2,6-bisphosphate in mammary gland of fed, starved and re-fed lactating rats

1985 ◽  
Vol 232 (3) ◽  
pp. 931-934 ◽  
Author(s):  
S Ward ◽  
N J Kuhn
Keyword(s):  
Mammary Gland ◽  
Intracellular Concentration ◽  
Limiting Factor ◽  
Maximal Rate ◽  
Physiological Conditions ◽  
Highly Sensitive ◽  
Lactating Mammary Gland ◽  
Rate Limiting

The fructose 2,6-bisphosphate (Fru-2,6-P2) content and intracellular concentration of lactating mammary gland was measured in fed, starved and re-fed rats. There was little or no change on starvation, and about 1.5-fold rise on re-feeding, contrasting with estimated glycolytic changes of about 10-fold. The 6-phosphofructokinase (PFK-1) activity of mammary extracts was highly sensitive to added Fru-2,6-P2 under all conditions examined, and appeared to approach saturation at physiological concentrations of this effector. The activity of mammary PFK-1 measured under optimal and ‘physiological’ conditions suggested that this enzyme operates in vivo at about 24% of maximal rate, and is likely to be an important rate-limiting factor in mammary glycolysis.

scholarly journals THE ROLE OF PNEUMATIC TUBE SYSTEM IN EFFICIENCY OF EMERGENCY LABORATORY SERVICE OF THE HOSPITAL

2018 ◽  
Vol 19 (3) ◽  
pp. 40-44
Author(s):  
V. M. Teplov ◽  
E. A. Karpova ◽  
Yu. P. Kovalchuk ◽  
I. P. Minnullin ◽  
S. S. Komedev ◽  
...  
Keyword(s):  
Blood Test ◽  
Laboratory Tests ◽  
Limiting Factor ◽  
Test Results ◽  
Tube System ◽  
Laboratory Service ◽  
Pneumatic Tube ◽  
Rate Limiting ◽  
Pneumatic Tube System

Laboratory tests are one of the most commonly ordered tests in the ED and often the rate-limiting  factor in the workup of a patient. The pneumatic tube system (PTS) can use to provide quick specimen  delivery. First aim of this study was to assess PTS by comparing routine chemistry, hematology, coagulation  blood test results and sample integrity indices between duplicate samples transported either manually or  automatically. Also we tried to assess the contribution of PTS to reduction in lab turnaround times.

scholarly journals Participation of the Ubiquitin-Conjugating Enzyme UBE2E3 in Nedd4-2-Dependent Regulation of the Epithelial Na+ Channel

2004 ◽  
Vol 24 (6) ◽  
pp. 2397-2409 ◽  
Author(s):  
Christophe Debonneville ◽  
Olivier Staub
Keyword(s):  
Binding Sites ◽  
Regulatory Mechanism ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Na Channel ◽  
Limiting Factor ◽  
Ubiquitin Conjugating Enzyme ◽  
Rate Limiting ◽  
Epithelial Na Channel

ABSTRACT The epithelial Na+ channel (ENaC) is a heteromeric protein complex playing a fundamental role in Na+ homeostasis and blood pressure regulation. Specific mutations inactivating PY motifs in ENaC C termini cause Liddle's syndrome, an inherited form of hypertension. Previously we showed that these PY motifs serve as binding sites for the E3 enzyme Nedd4-2, implying ubiquitination as a regulatory mechanism of ENaC. Ubiquitination involves the sequential action of E1, E2, and E3 enzymes. Here we identify the E2 enzyme UBE2E3, which acts in concert with Nedd4-2, and show by coimmunoprecipitation that UBE2E3 and Nedd4-2 interact together. In Xenopus laevis oocytes, UBE2E3 reduces ENaC activity marginally, consistent with Nedd4-2 being the rate-limiting factor in this process, whereas a catalytically inactive mutant of UBE2E3 (UBE2E3-CS) causes elevated ENaC activity by increasing cell surface expression. No additive effect is observed when UBE2E3-CS is coexpressed with an inactive Nedd4-2 mutant, and the stimulatory role of UBE2E3-CS depends on the integrity of the PY motifs (Nedd4-2 binding sites) and the ubiquitination sites on ENaC. In renal mpkCCDcl4 cells, displaying ENaC-dependent transepithelial Na+ transport, Nedd4-2 and UBE2E3 can be coimmunoprecipitated and overexpression of UBE2E3 affects Na+ transport, corroborating the concept of a concerted action of UBE2E3 and Nedd4-2 in ENaC regulation.

scholarly journals A novel zebrafish intestinal tumor model reveals a role for cyp7a1-dependent tumor-liver crosstalk in tumor's adverse effects on host

2017 ◽  
Author(s):  
Sora Enya ◽  
Koichi Kawakami ◽  
Yutaka Suzuki ◽  
Shinpei Kawaoka
Keyword(s):  
Tumor Model ◽  
Host Gene ◽  
Limiting Factor ◽  
Intestinal Tumor ◽  
Liver Inflammation ◽  
Growth Defects ◽  
Rate Limiting ◽  
Important Basis ◽  
Host Genes

AbstractThe nature of host organs and genes that underlie tumor-induced physiological disruption on host remains ill-defined. Here, we establish a novel zebrafish intestinal tumor model that is optimized for addressing this issue, and find that hepatic cyp7a1, the rate-limiting factor for synthesizing bile acids (BAs), is such a host gene. Inducing krasG12D by Gal4 specifically expressed in the posterior intestine resulted in formation of an intestinal tumor classified as dysplasia. The local intestinal tumor caused systemic detrimental effects on host including liver inflammation, hepatomegaly, growth defects, and organismal death. Whole-organismal level gene expression analysis and metabolite measurements revealed that the intestinal tumor reduced total BAs levels via down-regulation of hepatic cyp7a1. Genetically rescuing cyp7a1 expression in the liver restored the BAs synthesis and ameliorated tumor-induced liver inflammation, but not other tumor-dependent phenotypes. Thus, we found a previously unknown role of cyp7a1 as the host gene that links the intestinal tumor, hepatic cholesterol-BAs metabolism, and liver inflammation in tumor-bearing fish. Our model provides an important basis to discover host genes responsible for tumor-induced phenotypes and to uncover mechanisms underlying how tumors adversely affect host organisms.

scholarly journals The Potential Role of Changes in the Glucose and Lipid Metabolic Pathways in Gastrointestinal Cancer Progression: Strategy in Cancer Therapy

2021 ◽  
pp. 1-8
Author(s):  
Gordon A. Ferns ◽  
Milad Shahini Shams Abadi ◽  
Ahmad Raeisi ◽  
Mohammad-Hassan Arjmand
Keyword(s):  
Cancer Progression ◽  
Metabolic Pathways ◽  
Cell Metabolism ◽  
Tumor Formation ◽  
High Rate ◽  
Metabolic Inhibitors ◽  
Chemotherapy Drugs ◽  
Poor Outcomes ◽  
Rate Limiting

<b><i>Background:</i></b> Changes in cell metabolism are a well-known feature of some cancers, and this may be involved in the etiology of tumor formation and progression, as well as tumor heterogeneity. These changes may affect fatty acid metabolism and glycolysis and are required to provide the increase in energy necessary for the high rate of proliferation of cancer cells. Gastrointestinal cancers remain a difficult-to-treat cancer, particularly as they are usually diagnosed at a late stage of disease and are associated with poor outcomes. <b><i>Summary:</i></b> Recently, the changes in the metabolic pathways, including the expression of the rate-limiting enzymes involved, have been considered to be a potential target for therapy for gastrointestinal tumors. <b><i>Key Message:</i></b> A combination of routine chemotherapy drugs with metabolic inhibitors may improve the effectiveness of treatment.

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