metabolic turnover
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2021 ◽  
pp. 101294
Author(s):  
Paulo A. Gameiro ◽  
Vesela Encheva ◽  
Mariana Silva Dos Santos ◽  
James I. MacRae ◽  
Jernej Ule

Author(s):  
Ririko Takeda ◽  
Ariful Islam ◽  
Tomohito Sato ◽  
Hiroki Kurita ◽  
Tomoaki Kahyo ◽  
...  

Proceedings ◽  
2020 ◽  
Vol 62 (1) ◽  
pp. 5
Author(s):  
Oksana Lockridge ◽  
Lawrence M. Schopfer

The genes for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) encode the proteins responsible for enzyme activity. Additional gene products, PRiMA and ColQ, anchor AChE and BChE proteins into membranes. Soluble AChE and BChE tetramers are composed of four identical subunits plus one polyproline-rich peptide. Dilution does not release the polyproline-rich peptide from tetramers. However, protein denaturation, for example, heating in a boiling water bath, dissociates the polyproline-rich peptide. Using mass spectrometry to sequence peptides released from soluble AChE and BChE tetramers, we find sequences that correspond to proline-rich regions from a variety of proteins. A typical peptide sequence contains 20 consecutive prolines in a 23-residue peptide, LPPPPPPPPPPPPPPPPPPPPLP. There is no single, common consensus sequence, i.e., no specific gene appears to be responsible for the polyproline-rich peptides found in soluble AChE and BChE tetramers. We propose that during metabolic turnover, protein fragments containing polyproline-rich sequences are scavenged by AChE and BChE dimers, to make stable AChE and BChE tetramers. The 40-residue, alpha-helical C-terminus of AChE or BChE is the tetramerization domain that binds the polyproline-rich peptide. Four parallel alpha helices wrap around a single antiparallel polyproline peptide to lock the tetramer in place. This organization was established by classical X-ray crystallography for isolated C-termini in complex with a proline-rich peptide. The organization was confirmed for intact, tetrameric human BChE using cryoelectron microscopy. When 40 amino acids are deleted from the carboxy terminus, monomeric enzymes are created that retain full enzymatic activity.


Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4515
Author(s):  
Stephen B. Shears ◽  
Huanchen Wang

Inositol pyrophosphates (PP-InsPs) comprise an important group of intracellular, diffusible cellular signals that a wide range of biological processes throughout the yeast, plant, and animal kingdoms. It has been difficult to gain a molecular-level mechanistic understanding of the actions of these molecules, due to their highly phosphorylated nature, their low levels, and their rapid metabolic turnover. More recently, these obstacles to success are being surmounted by the chemical synthesis of a number of insightful PP-InsP analogs. This review will describe these analogs and will indicate the important chemical and biological information gained by using them.


2020 ◽  
Vol 61 (4) ◽  
pp. 523-536 ◽  
Author(s):  
Kotaro Hama ◽  
Yuko Fujiwara ◽  
Shigeo Takashima ◽  
Yasuhiro Hayashi ◽  
Atsushi Yamashita ◽  
...  

X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder caused by deleterious mutations in the ABCD1 gene. The ABCD1 protein transports very long-chain FAs (VLCFAs) from the cytosol into the peroxisome where the VLCFAs are degraded through β-oxidation. ABCD1 dysfunction leads to VLCFA accumulation in individuals with X-ALD. FAs are activated by esterification to CoA before metabolic utilization. However, the intracellular pools and metabolic profiles of individual acyl-CoA esters have not been fully analyzed. In this study, we profiled the acyl-CoA species in fibroblasts from X-ALD patients and in ABCD1-deficient HeLa cells. We found that hexacosenoyl (26:1)-CoA, but not hexacosanoyl (26:0)-CoA, was the most abundantly concentrated among the VLCFA-CoA species in these cells. We also show that 26:1-CoA is mainly synthesized from oleoyl-CoA, and the metabolic turnover rate of 26:1-CoA was almost identical to that of oleoyl-CoA in both WT and ABCD1-deficient HeLa cells. The findings of our study provide precise quantitative and metabolic information of each acyl-CoA species in living cells. Our results suggest that VLCFA is endogenously synthesized as VLCFA-CoA through a FA elongation pathway and is then efficiently converted to other metabolites, such as phospholipids, in the absence of ABCD1.


Author(s):  
John Dupré ◽  
Daniel J. Nicholson

This chapter argues that scientific and philosophical progress in our understanding of the living world requires that we abandon a metaphysics of things in favour of one centred on processes. We identify three main empirical motivations for adopting a process ontology in biology: metabolic turnover, life cycles, and ecological interdependence. We show how taking a processual stance in the philosophy of biology enables us to ground existing critiques of essentialism, reductionism, and mechanicism, all of which have traditionally been associated with substance ontology. We illustrate the consequences of embracing an ontology of processes in biology by considering some of its implications for physiology, genetics, evolution, and medicine. And we attempt to locate the subsequent chapters of the book in relation to the position we defend.


2017 ◽  
Vol 283 ◽  
pp. 33-44 ◽  
Author(s):  
Hao Chen ◽  
Henk M. De Feyter ◽  
Peter B. Brown ◽  
Douglas L. Rothman ◽  
Shuhui Cai ◽  
...  

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