scholarly journals Fatty acid activation in carcinogenesis and cancer development: Essential roles of long‑chain acyl‑CoA synthetases (Review)

2018 ◽  
Author(s):  
Yue Tang ◽  
Jing Zhou ◽  
Shing Hooi ◽  
Yue‑Ming Jiang ◽  
Guo‑Dong Lu
Keyword(s):  
Fatty Acid ◽  
Cancer Development ◽  
Acid Activation ◽  
Chain Acyl ◽  
Fatty Acid Activation ◽  
Long Chain

scholarly journals Saccharomyces cerevisiae contains four fatty acid activation (FAA) genes: an assessment of their role in regulating protein N-myristoylation and cellular lipid metabolism.

1994 ◽  
Vol 127 (3) ◽  
pp. 751-762 ◽  
Author(s):  
D R Johnson ◽  
L J Knoll ◽  
D E Levin ◽  
J I Gordon
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Carbon Source ◽  
Vegetative Growth ◽  
Fatty Acid Synthetase ◽  
Acid Activation ◽  
Beta Oxidation ◽  
Fatty Acid Activation ◽  
Long Chain

Saccharomyces cerevisiae has been used as a model for studying the regulation of protein N-myristoylation. MyristoylCoA:protein N-myristoyl-transferase (Nmt1p), is essential for vegetative growth and uses myristoylCoA as its substrate. MyristoylCoA is produced by the fatty acid synthetase (Fas) complex and by cellular acylCoA synthetases. We have recently isolated three unlinked Fatty Acid Activation (FAA) genes encoding long chain acylCoA synthetases and have now recovered a fourth by genetic complementation. When Fas is active and NMT1 cells are grown on media containing a fermentable carbon source, none of the FAA genes is required for vegetative growth. When Fas is inactivated by a specific inhibitor (cerulenin), NMT1 cells are not viable unless the media is supplemented with long chain fatty acids. Supplementation of cellular myristoylCoA pools through activation of imported myristate (C14:0) is predominantly a function of Faa1p, although Faa4p contributes to this process. Cells with nmt181p need larger pools of myristoylCoA because of the mutant enzyme's reduced affinity for this substrate. Faa1p and Faa4p are required for maintaining the viability of nmt1-181 strains even when Fas is active. Overexpression of Faa2p can rescue nmt1-181 cells due to activation of an endogenous pool of C14:0. This pool appears to be derived in part from membrane phospholipids since overexpression of Plb1p, a nonessential lysophospholipase/phospholipase B, suppresses the temperature-sensitive growth arrest and C14:0 auxotrophy produced by nmt1-181. None of the four known FAAs is exclusively responsible for targeting imported fatty acids to peroxisomal beta-oxidation pathways. Introduction of a peroxisomal assembly mutation, pas1 delta, into isogenic NMT1 and nmt1-181 strains with wild type FAA alleles revealed that when Fas is inhibited, peroxisomes contribute to myristoylCoA pools used by Nmt1p. When Fas is active, a fraction of cellular myristoylCoA is targeted to peroxisomes. A NMT1 strain with deletions of all four FAAs is still viable at 30 degrees C on media containing myristate, palmitate, or oleate as the sole carbon source--indicating that S. cerevisiae contains at least one other FAA which directs fatty acids to beta-oxidation pathways.

scholarly journals Palmitoyl-coenzyme A synthetase. Mechanism of reaction

1973 ◽  
Vol 131 (2) ◽  
pp. 199-209 ◽  
Author(s):  
J. Bar–Tana ◽  
G. Rose ◽  
R. Brandes ◽  
B. Shapiro
Keyword(s):  
Fatty Acid ◽  
Chain Fatty Acid ◽  
Acid Activation ◽  
Long Chain Fatty Acid ◽  
Mechanism Of Reaction ◽  
Ping Pong ◽  
Fatty Acid Activation ◽  
Kinetics Of ◽  
Enzyme Intermediate ◽  
Long Chain

The mechanism of long-chain fatty acid activation catalysed by highly purified microsomal palmitoyl-CoA synthetase was investigated. The kinetics of the overall reaction were found to conform to the Bi Uni Uni Bi Ping Pong mechanism. 18O was transferred from [18O]palmitate to AMP and palmitoyl-CoA exclusively. The enzyme intermediate formed appeared to consist of enzyme-bound palmitate; this formation occurred only in the presence of ATP. However, the involvement of palmitoyl-AMP in the reaction catalysed by the purified enzyme has proved difficult to establish.

scholarly journals Microsomal palmitoyl-coenzyme A synthetase from rat liver. Partial and exchange reactions

1972 ◽  
Vol 129 (5) ◽  
pp. 1101-1107 ◽  
Author(s):  
J. Bar–Tana ◽  
G. Rose ◽  
B. Shapiro
Keyword(s):  
Fatty Acid ◽  
Microsomal Fraction ◽  
Fatty Acyl ◽  
Chain Fatty Acid ◽  
Acid Activation ◽  
Exchange Reactions ◽  
Long Chain Fatty Acid ◽  
Atp Formation ◽  
Fatty Acid Activation ◽  
Long Chain

The partial and exchange reactions of long-chain fatty acid activation were determined by using purified microsomal long-chain fatty acyl-CoA synthetase (EC 6.2.1.3). No significant ATP formation from palmitoyl-AMP and PPi, nor palmitoyl-AMP-dependent CoA disappearance could be demonstrated. Similarly, no palmitate-dependent [32P2]PPi–ATP exchange was catalysed by the pure enzyme. The above partial and exchange reactions were, however, catalysed by the parent microsomal fraction at a rate similar to that of the overall reaction. The implications of these results are discussed.

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