scholarly journals Ceramide turnover in GtoPdb v.2021.3

2021 ◽  
Vol 2021 (3) ◽  
Author(s):  
Anthony H. Futerman
Keyword(s):  
Endoplasmic Reticulum ◽  
Kinetic Parameters ◽  
Metabolic Pathway ◽  
Stress Responses ◽  
Cell Stress ◽  
Serine Palmitoyltransferase ◽  
Transfer Protein ◽  
Multiple Routes ◽  
Mediate Cell

Ceramides are a family of sphingophospholipids synthesized in the endoplasmic reticulum, which mediate cell stress responses, including apoptosis, autophagy and senescence, Serine palmitoyltransferase generates 3-ketosphinganine, which is reduced to dihydrosphingosine. N-Acylation allows the formation of dihydroceramides, which are subsequently reduced to form ceramides. Once synthesized, ceramides are trafficked from the ER to the Golgi bound to the ceramide transfer protein, CERT (COL4A3BP, Q9Y5P4). Ceramide can be metabolized via multiple routes, ensuring tight regulation of its cellular levels. Addition of phosphocholine generates sphingomyelin while carbohydrate is added to form glucosyl- or galactosylceramides. Ceramidase re-forms sphingosine or sphinganine from ceramide or dihydroceramide. Phosphorylation of ceramide generates ceramide phosphate. The determination of accurate kinetic parameters for many of the enzymes in the sphingolipid metabolic pathway is complicated by the lipophilic nature of the substrates.

scholarly journals Ceramide turnover (version 2020.5) in the IUPHAR/BPS Guide to Pharmacology Database

2020 ◽  
Vol 2020 (5) ◽  
Author(s):  
Anthony H. Futerman
Keyword(s):  
Endoplasmic Reticulum ◽  
Kinetic Parameters ◽  
Metabolic Pathway ◽  
Stress Responses ◽  
Cell Stress ◽  
Serine Palmitoyltransferase ◽  
Transfer Protein ◽  
Multiple Routes ◽  
Mediate Cell

Ceramides are a family of sphingophospholipids synthesized in the endoplasmic reticulum, which mediate cell stress responses, including apoptosis, autophagy and senescence, Serine palmitoyltransferase generates 3-ketosphinganine, which is reduced to dihydrosphingosine (dihydrosphingosine). N-Acylation allows the formation of dihydroceramides, which are subsequently reduced to form ceramides. Once synthesized, ceramides are trafficked from the ER to the Golgi bound to the ceramide transfer protein, CERT (COL4A3BP, Q9Y5P4). Ceramide can be metabolized via multiple routes, ensuring tight regulation of its cellular levels. Addition of phosphocholine generates sphingomyelin while carbohydrate is added to form glucosyl- or galactosylceramides. Ceramidase re-forms sphingosine or sphinganine from ceramide or dihydroceramide. Phosphorylation of ceramide generates ceramide phosphate. The determination of accurate kinetic parameters for many of the enzymes in the sphingolipid metabolic pathway is complicated by the lipophilic nature of the substrates.

scholarly journals Ceramide turnover (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
Anthony H. Futerman
Keyword(s):  
Endoplasmic Reticulum ◽  
Kinetic Parameters ◽  
Metabolic Pathway ◽  
Stress Responses ◽  
Cell Stress ◽  
Serine Palmitoyltransferase ◽  
Transfer Protein ◽  
Multiple Routes ◽  
Mediate Cell

Ceramides are a family of sphingophospholipids synthesized in the endoplasmic reticulum, which mediate cell stress responses, including apoptosis, autophagy and senescence, Serine palmitoyltransferase generates 3-ketosphinganine, which is reduced to sphinganine (dihydrosphingosine). N-Acylation allows the formation of dihydroceramides, which are subsequently reduced to form ceramides. Once synthesized, ceramides are trafficked from the ER to the Golgi bound to the ceramide transfer protein, CERT (COL4A3BP, Q9Y5P4). Ceramide can be metabolized via multiple routes, ensuring tight regulation of its cellular levels. Addition of phosphocholine generates sphingomyelin while carbohydrate is added to form glucosyl- or galactosylceramides. Ceramidase re-forms sphingosine or sphinganine from ceramide or dihydroceramide. Phosphorylation of ceramide generates ceramide phosphate. The determination of accurate kinetic parameters for many of the enzymes in the sphingolipid metabolic pathway is complicated by the lipophilic nature of the substrates.

scholarly journals Identification and dynamics of the human ZDHHC16-ZDHHC6 palmitoylation cascade

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Laurence Abrami ◽  
Tiziano Dallavilla ◽  
Patrick A Sandoz ◽  
Mustafa Demir ◽  
Béatrice Kunz ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Mathematical Modelling ◽  
Experimental Determination ◽  
Kinetic Parameters ◽  
Turnover Rate ◽  
Data Driven ◽  
Lipid Modification ◽  
Site Specific

S-Palmitoylation is the only reversible post-translational lipid modification. Knowledge about the DHHC palmitoyltransferase family is still limited. Here we show that human ZDHHC6, which modifies key proteins of the endoplasmic reticulum, is controlled by an upstream palmitoyltransferase, ZDHHC16, revealing the first palmitoylation cascade. The combination of site specific mutagenesis of the three ZDHHC6 palmitoylation sites, experimental determination of kinetic parameters and data-driven mathematical modelling allowed us to obtain detailed information on the eight differentially palmitoylated ZDHHC6 species. We found that species rapidly interconvert through the action of ZDHHC16 and the Acyl Protein Thioesterase APT2, that each species varies in terms of turnover rate and activity, altogether allowing the cell to robustly tune its ZDHHC6 activity.

scholarly journals Identification and dynamics of the DHHC16-DHHC6 palmitoylation cascade

2017 ◽  
Author(s):  
Laurence Abrami ◽  
Tiziano Dallavilla ◽  
Patrick A. Sandoz ◽  
Mustafa Demir ◽  
Béatrice Kunz ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Mathematical Modelling ◽  
Experimental Determination ◽  
Kinetic Parameters ◽  
Turnover Rate ◽  
Data Driven ◽  
Lipid Modification ◽  
Site Specific

ABSTRACTS-Palmitoylation is the only reversible post-translational lipid modification. Knowledge about the DHHC family of palmitoyltransferases is very limited. Here we show that mammalian DHHC6, which modifies key proteins of the endoplasmic reticulum, is controlled by an upstream palmitoyltransferase, DHHC16, revealing the first palmitoylation cascade. Combination of site specific mutagenesis of the three DHHC6 palmitoylation sites, experimental determination of kinetic parameters and data-driven mathematical modelling allowed us to obtain detailed information on the 8 differentially palmitoylated DHHC6 species. We found that species rapidly interconvert through the action of DHHC16 and the Acyl Protein Thioesterase APT2, that each species varies in terms of turnover rate and activity, altogether allowing the cell to robustly tune its DHHC6 activity.

MEASUREMENT OF STEROID BINDING PROTEINS

1970 ◽  
Vol 65 (1_Suppl) ◽  
pp. S104-S121 ◽  
Author(s):  
E. E. Baulieu ◽  
J. P. Raynaud ◽  
E. Milgrom
Keyword(s):  
Kinetic Parameters ◽  
Binding Proteins ◽  
Binding Specificity ◽  
Binding Parameters ◽  
Target Organs ◽  
Biological Mixtures ◽  
Steroid Binding Proteins ◽  
Steroid Binding ◽  
Steroid Binding Protein

ABSTRACT A brief review of the characteristics of steroid binding proteins found in the plasma and in some target organs is presented, followed by some general remarks on binding »specificity« and binding parameters. Useful techniques for measuring binding parameters at equilibrium are reported, both those which keep the equilibrium intact and those which implicate its disruption. A concept is developed according to which the determination of a specific steroid binding protein is based on the »differential dissociation« of the several steroid binding complexes present in most biological mixtures. Methods which allow determination of the kinetic parameters of the binding systems are also presented. Various representations of the binding and therefore different modes of graphic representation and calculation are discussed, including the recent »proportion graph« method.

Regeneration Mechanism Studied by Potential-Time Response to Sinusoidal Current-Time Function

1997 ◽  
Vol 62 (10) ◽  
pp. 1511-1526
Author(s):  
María-Luisa Alcaraz ◽  
Ángela Molina
Keyword(s):  
Kinetic Parameters ◽  
Rate Constant ◽  
Theoretical Study ◽  
Time Function ◽  
Time Response ◽  
Current Time ◽  
Regeneration Mechanism ◽  
Sinusoidal Current ◽  
Regeneration Processes

A theoretical study of the potential-time response to sinusoidal current applied to static and dynamic electrodes for regeneration processes is presented. Methods for determination of the regeneration fraction, rate constant of the chemical reaction and heterogeneous kinetic parameters are proposed.

scholarly journals Crosstalk between endoplasmic reticulum stress and oxidative stress: a dynamic duo in multiple myeloma

2021 ◽  
Author(s):  
Sinan Xiong ◽  
Wee-Joo Chng ◽  
Jianbiao Zhou
Keyword(s):  
Oxidative Stress ◽  
Multiple Myeloma ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Cell Fate ◽  
Stress Responses ◽  
Plasma Cells ◽  
Reactive Oxygen Species Generation ◽  
Future Research ◽  
And Oxidative Stress

AbstractUnder physiological and pathological conditions, cells activate the unfolded protein response (UPR) to deal with the accumulation of unfolded or misfolded proteins in the endoplasmic reticulum. Multiple myeloma (MM) is a hematological malignancy arising from immunoglobulin-secreting plasma cells. MM cells are subject to continual ER stress and highly dependent on the UPR signaling activation due to overproduction of paraproteins. Mounting evidence suggests the close linkage between ER stress and oxidative stress, demonstrated by overlapping signaling pathways and inter-organelle communication pivotal to cell fate decision. Imbalance of intracellular homeostasis can lead to deranged control of cellular functions and engage apoptosis due to mutual activation between ER stress and reactive oxygen species generation through a self-perpetuating cycle. Here, we present accumulating evidence showing the interactive roles of redox homeostasis and proteostasis in MM pathogenesis and drug resistance, which would be helpful in elucidating the still underdefined molecular pathways linking ER stress and oxidative stress in MM. Lastly, we highlight future research directions in the development of anti-myeloma therapy, focusing particularly on targeting redox signaling and ER stress responses.

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