scholarly journals Cryptosporidium parvum Long-Chain Fatty Acid Elongase

2007 ◽  
Vol 6 (11) ◽  
pp. 2018-2028 ◽  
Author(s):  
Jason M. Fritzler ◽  
Jason J. Millership ◽  
Guan Zhu
Keyword(s):  
Fatty Acid ◽  
Functional Characterization ◽  
Fatty Acyl ◽  
Chain Fatty Acid ◽  
Type I ◽  
Long Chain Fatty Acid ◽  
Fatty Acid Elongase ◽  
Key Enzyme ◽  
Acyl Coenzyme A ◽  
Long Chain

ABSTRACT We report the presence of a new fatty acyl coenzyme A (acyl-CoA) elongation system in Cryptosporidium and the functional characterization of the key enzyme, a single long-chain fatty acid elongase (LCE), in this parasite. This enzyme contains conserved motifs and predicted transmembrane domains characteristic to the elongase family and is placed within the ELO6 family specific for saturated substrates. CpLCE1 gene transcripts are present at all life cycle stages, but the levels are highest in free sporozoites and in stages at 36 h and 60 h postinfection that typically contain free merozoites. Immunostaining revealed localization to the outer surface of sporozoites and to the parasitophorous vacuolar membrane. Recombinant CpLCE1 displayed allosteric kinetics towards malonyl-CoA and palmitoyl-CoA and Michaelis-Menten kinetics towards NADPH. Myristoyl-CoA (C14:0) and palmitoyl-CoA (C16:0) display the highest activity when used as substrates, and only one round of elongation occurs. CpLCE1 is fairly resistant to cerulenin, an inhibitor for both type I and II fatty acid synthases (i.e., maximum inhibitions of 20.5% and 32.7% were observed when C16:0 and C14:0 were used as substrates, respectively). These observations ultimately validate the function of CpLCE1.

scholarly journals Two Italian Patients with ELOVL4-Related Neuro-Ichthyosis:  Expanding the Genotypic and Phenotypic Spectrum and Ultrastructural Characterization

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 343
Author(s):  
Andrea Diociaiuti ◽  
Diego Martinelli ◽  
Francesco Nicita ◽  
Claudia Cesario ◽  
Elisa Pisaneschi ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Chain Fatty Acid ◽  
Spinocerebellar Ataxia Type ◽  
Facial Dysmorphism ◽  
Macular Dystrophy ◽  
Compound Heterozygous ◽  
Long Chain Fatty Acid ◽  
Fatty Acid Elongase ◽  
Spastic Quadriplegia ◽  
Long Chain

Elongation of Very Long Chain Fatty Acid-4 (ELOVL4) is a fatty acid elongase responsible for very long-chain fatty acid biosynthesis in the brain, retina, and skin. Heterozygous mutations in ELOVL4 gene cause Stargardt-like macular dystrophy and spinocerebellar ataxia type-34, while different homozygous mutations have been associated with ichthyosis, spastic quadriplegia, and mental retardation syndrome in three kindred. We report the first two Italian children affected with neuro-ichthyosis due to the previously undescribed ELOVL4 homozygous frameshift variant c.435dupT (p.Ile146TyrfsTer29), and compound heterozygous variants c.208C>T (p.Arg70Ter) and c.487T>C (p.Cys163Arg), respectively. Both patients were born with collodion membrane followed by development of diffuse mild hyperkeratosis and scaling, localized erythema, and palmoplantar keratoderma. One infant displayed mild facial dysmorphism. They suffered from failure to thrive, and severe gastro-esophageal reflux with pulmonary aspiration. The patients presented axial hypotonia, hypertonia of limbs, and absent head control with poor eye contact from infancy. Visual evoked potentials showed markedly increased latency and poor morphological definition, indicative of alteration of the retro-retinal visual pathways in both patients. Ultrastructural skin examination revealed abnormalities of lamellar bodies with altered release in the epidermal granular and horny layer intracellular spaces. Our findings contribute to expanding the phenotypic and genotypic features of ELOVL4-related neuro-ichthyosis.

Glucose-6-phosphate dehydrogenase from Neisseria gonorrhoeae: partial characterization of the enzyme and inhibition by long-chain fatty acid acyl-coenzyme A derivatives

1980 ◽  
Vol 26 (8) ◽  
pp. 863-873 ◽  
Author(s):  
Anthony F. Cacciapuoti ◽  
Stephen A. Morse
Keyword(s):  
Fatty Acid ◽  
Neisseria Gonorrhoeae ◽  
Coenzyme A ◽  
Energy Charge ◽  
Chain Fatty Acid ◽  
Adenylate Energy Charge ◽  
Long Chain Fatty Acid ◽  
Acyl Coenzyme A ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Long Chain

The glucose-6-phosphate dehydrogenase from Neisseria gonorrhoeae was inhibited by long-chain fatty acid acyl-coenzyme A derivatives. The inhibition was increased at low concentrations of glucose 6-phosphate and was greater with the NAD-linked activity (ca. 0.05 mM inhibitor required for 50% inhibition) than with the NADP-linked activity (ca. 0.2 mM required for 50% inhibition). Bovine serum albumin and spermine could prevent the inhibition by the acyl-coenzyme A derivatives, but neither of these compounds nor high concentrations of cofactors or substrate could reverse the effect. Dilution of enzyme–inhibitor preincubation mixtures appeared to reverse the inhibition. The inhibition by stearoyl-coenzyme A was of the mixed type, and the inhibitor appeared to have a greater affinity for the free enzyme (Ki = 0.016–0.05 mM) than for enzyme bound to cofactor or substrate (Kis = 0.07–0.08 mM). Glucose-6-phosphate dehydrogenase activity was also inhibited competitively by adenosine 5′-triphosphate and was strongly regulated by adenylate energy charge values between 0.9 and 1.0. Kinetic and other characteristics of the enzyme are presented, and the possible role of glucose-6-phosphate dehydrogenase as a target for fatty acid toxicity in gonococci, mediated in the form of the acyl-coenzyme A derivatives, is discussed.

High-Fat Diet Elevates Liver Docosahexaenoic Acid Possibly through Over-Expression of Very Long-Chain Fatty Acid Elongase 2 in C57BL/6J Mice

2019 ◽  
Vol 89 (1-2) ◽  
pp. 62-72
Author(s):  
Mooli Raja Gopal Reddy ◽  
Gundluri Venkata Asha ◽  
Sravan Kumar Manchiryala ◽  
Uday Kumar Putcha ◽  
Ayyalasomayajula Vajreswari ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
High Fat Diet ◽  
Chain Fatty Acid ◽  
High Fat ◽  
Long Chain Fatty Acid ◽  
Fatty Acid Elongase ◽  
Over Expression ◽  
Long Chain

Abstract. The liver is the main site of lipid metabolism and vitamin A storage. Dietary factors are known to affect liver function, thereby leading to metabolic abnormalities. Here, we assessed the impact of long-term feeding of a high-fat diet on hepatic vitamin A status and lipid metabolism. For this purpose, 14 male and 14 female 35-day-old mice (strain C57BL/6J) were each divided into 2 groups of 7 animals and fed either a stock diet or a high-fat (HF) diet for 26 weeks. In addition to increased body weight/weight gain, the HF diet induced hypertriglyceridemia in both (p < 0.01). However, liver triglyceride levels were comparable among groups, which could be partly explained by unaltered expression of various lipogenic pathway proteins such as sterol regulatory element binding protein 1 (SREBP1), fatty acid synthase (FAS), microsomal triglyceride transfer protein (MTTP), and glycerol 3-phosphate acyl transferase (GPAT). On the other hand, hepatic retinol stores increased significantly in both sexes, whereas males displayed elevated circulatory retinol levels. Notably, long-term feeding of a HF diet elevated n-3 polyunsaturated fatty acid (PUFA) and docosahexaenoic acid (DHA, C22:6) levels in the liver (p ≤ 0.001), which is in line with the over-expression of very long-chain fatty acid elongase 2 (ELOVL2) protein in both sexes of mice (p < 0.01). In conclusion, very long-term feeding of a HF diet increased hepatic retinol stores and induced hypertriglyceridemia. However, it had no effect on hepatic triglyceride accumulation, possibly due to increased DHA levels arising from the ELOVL2-mediated elongation pathway.

scholarly journals Disruption of theSaccharomyces cerevisiae FAT1Gene Decreases Very Long-chain Fatty Acyl-CoA Synthetase Activity and Elevates Intracellular Very Long-chain Fatty Acid Concentrations

1998 ◽  
Vol 273 (29) ◽  
pp. 18210-18219 ◽  
Author(s):  
Paul A. Watkins ◽  
Jyh-Feng Lu ◽  
Steven J. Steinberg ◽  
Stephen J. Gould ◽  
Kirby D. Smith ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acyl ◽  
Chain Fatty Acid ◽  
Synthetase Activity ◽  
Long Chain Fatty Acid ◽  
Long Chain
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