scholarly journals Alternative route for the biosynthesis of polyunsaturated fatty acids in K562 cells

1993 ◽  
Vol 291 (3) ◽  
pp. 841-845 ◽  
Author(s):  
J Naval ◽  
M J Martínez-Lorenzo ◽  
I Marzo ◽  
P Desportes ◽  
A Piñeiro

K562 human leukaemia cells lack a significant delta 6-desaturase activity. However, they synthesize long-chain polyunsaturated fatty acids (PUFA) from linoleic (C18:2(9,12)) and linolenic (C18:3(9,12,15)) acids, by reactions involving a C2 chain elongation followed by a delta 5-desaturation step and, to some extent, a further elongation. The main products formed were separated by argentation t.l.c. and identified by g.l.c. as the uncommon fatty acids C20:3(5,11,14) and C20:4(5,11,14,17) respectively. These acids were also produced when cells were supplemented with C20:2(11,14) or C20:3(11,14,17) respectively. The presence of a delta 5-desaturase was further confirmed by using its corresponding normal substrates, C20:3(8,11,14) and C20:4(8,11,14,17), which led to C20:4(5,8,11,14) and C20:5(5,8,11,14,17) respectively. On the other hand, a high delta 9-desaturase activity, but no significant delta 4-desaturase activity, were detected in K562 cells. These results indicate the existence of an alternative pathway, involving delta 5-desaturase, which is the only route for PUFA biosynthesis in K562 cells. This pathway may be relevant for the biosynthesis of PUFA in cells lacking delta 6-desaturase activity.

Open Biology ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 190140 ◽  
Author(s):  
Lishuang Song ◽  
Lei Yang ◽  
Jiapeng Wang ◽  
Xuefei Liu ◽  
Lige Bai ◽  
...  

Linoleic acid (18 : 2, n-6) and α-linolenic acid (18 : 3, n-3) are polyunsaturated fatty acids (PUFAs), which are essential for mammalian health, development and growth. However, the majority of mammals, including humans, are incapable of synthesizing n-6 and n-3 PUFAs. Mammals must obtain n-6 and n-3 PUFAs from their diet. Fatty acid desaturase (Fad) plays a critical role in plant PUFA biosynthesis. Therefore, we generated plant-derived Fad3 single and Fad2–Fad3 double transgenic mice. Compared with wild-type mice, we found that PUFA levels were greatly increased in the single and double transgenic mice by measuring PUFA levels. Moreover, the concentration of n-6 and n-3 PUFAs in the Fad2–Fad3 double transgenic mice were greater than in the Fad3 single transgenic mice. These results demonstrate that the plant-derived Fad2 and Fad3 genes can be expressed in mammals. To clarify the mechanism for Fad2 and Fad3 genes in transgenic mice, we measured the PUFAs synthesis-related genes. Compared with wild-type mice, these Fad transgenic mice have their own n-3 and n-6 PUFAs biosynthetic pathways. Thus, we have established a simple and efficient method for in vivo synthesis of PUFAs.


1993 ◽  
Vol 71 (9) ◽  
pp. 683-683 ◽  
Author(s):  
M. T. Clandinin

Metabolism of long-chain polyunsaturated fatty acids derived from 18:2ω−6 and 18:3ω−3 by chain elongation – desaturation is essential for synthesis of complex structural lipids, leukotrienes, thromboxanes, and prostaglandins. These essential fatty acids are required for normal function in developing tissues and appropriate maturation of a wide variety of physiological processes. During development, fetal accretion of long-chain metabolites of ω−6 and ω−3 fatty acids may result from maternal or placental synthesis and transfer or, alternatively, from the metabolism of 18:2ω−6 and 18:3ω−3 to longer chain homologues by the fetus. After birth the infant must synthesize or be fed the very long chain polyunsaturated fatty acids of C20 and C22 type derived from 18:2ω−6 and 18:3ω−3.Metabolism of ω−6 and ω−3 fatty acids utilizes the same enzyme system and is competitive. When levels of dietary ω−3 and ω−6 C18 fatty acids are altered, the levels of metabolites of these precursor fatty acids change in specific brain membranes, influencing membrane lipid dependent functions. For example, a diet unbalanced in very long chain ω−3 and ω−6 fatty acids may increase brain membrane ω−3 fatty acid content when 20:5ω−3 is fed, while decreasing membrane fatty acid content of the ω−6 series of competing fatty acids. As 20:4ω−6 is quantitatively and qualitatively important to brain phospholipid, significant reduction in brain levels of 20:4ω−6 may be less than optimal. The impact of these compositional changes on brain function is not yet clear.The authors in this symposium address how this general area of essential fatty acid metabolism is relevant to the evolution of man, growth and development of fish, function of the retina and neural tissue, cognitive development of infants, and infant nutrition.


1982 ◽  
Vol 207 (1) ◽  
pp. 29-35 ◽  
Author(s):  
F H Faas ◽  
W J Carter

We have studied the influence of experimental hypothyroidism in the rat on the synthesis of unsaturated fatty acids and on liver microsomal lipid fatty acid composition. Hypothyroid rats demonstrated an 80% decrease in delta 9 (stearate) desaturation and a 43% decrease in delta 6 (linoleate) desaturation. Liver microsomal fatty acid composition was altered in the hypothyroid animals with a significantly decreased proportion of arachidonate and increased proportions of linoleate, eicosa-8,11,14-trienoate, eicosapentaenoate and docosahexaenoate. The bulk of these changes occurred in both of the two major phospholipid components, phosphatidylcholine and phosphatidylethanolamine. All of the changes were corrected by treatment of the hypothyroid rat with 25 micrograms of tri-iodothyronine/100 g body wt. twice daily. The diminished delta 9 desaturation did not lead to any changes in fatty acid composition. The increased linoleate and decreased arachidonate levels may be due to the diminished delta 6 desaturase activity, the rate-controlling step in the conversion of linoleate into arachidonate. The increases in the proportions of the other polyunsaturated fatty acid components cannot be explained by changes in the synthesis of unsaturated fatty acids, but are probably due to diminished utilization of these fatty acids.


2021 ◽  
Vol 168 (5) ◽  
Author(s):  
Supanut Pairohakul ◽  
Peter J. W. Olive ◽  
Matthew G. Bentley ◽  
Gary S. Caldwell

AbstractPolychaete worms are rich sources of polyunsaturated fatty acids (PUFA) and are increasingly incorporated into aquaculture broodstock diets. Conventionally, the build-up of PUFA in polychaetes was considered passive, with direct accumulation along the food web, originating with microalgae and other primary producers. However, it has been argued that polychaetes (and other multicellular eukaryotes) are capable of PUFA biosynthesis through the elongation and desaturation of precursor lipids. We further test this hypothesis in the ecologically and economically important nereid polychaete Alitta virens by adopting a stable isotope labelling approach. Worms were fed a 13C-1-palmitic acid (C16:0) enriched diet with the resulting isotopically enriched lipid products identified over a 7-day period. The data showed strong evidence of lipid elongation and desaturation, but with a high rate of PUFA turnover. A putative biosynthetic pathway is proposed, terminating with docosahexaenoic acid (DHA) via arachidonic (AA) and eicosapentaenoic acids (EPA) and involving a Δ8 desaturase.


1985 ◽  
Vol 225 (2) ◽  
pp. 307-313 ◽  
Author(s):  
S Hughes ◽  
D A York

Hepatic delta 6-desaturase activity is primarily located in the mitochondrial fraction in mice. Both delta 6- and delta 5-desaturase activities are increased in the liver of young (6-week-old) obese mice. The increase in hepatic delta 6-desaturase activity in obese mice does not occur until weaning. Neither restriction of food intake nor hyperinsulinaemia normalize hepatic delta 6-desaturase activity of obese mice. Both cold acclimation and tri-iodothyronine (30 micrograms/day per kg) decreased hepatic delta 6-desaturase activity of obese mice to levels observed in lean mice, whereas the increase in activity in obese mice was still maintained after the induction of hypothyroidism.


1985 ◽  
Vol 227 (3) ◽  
pp. 1021-1023 ◽  
Author(s):  
M T Clandinin ◽  
K Wong ◽  
R R Hacker

Microsomes isolated from liver and brain tissue were assayed to examine transitions in metabolic capability to synthesize tetraenes and pentaenes by chain elongation-desaturation of C20:3(8,11,14) during the perinatal development of the pig. Rates of synthesis of tetraenes and pentaenes by chain elongation-desaturation of C20:3(8,11,14) were greatest in liver. During the latter half of gestation, the capability to synthesize tetraenes increased 7- or 23-fold on a per mg of microsomal protein basis for brain and liver respectively. Increase in the capacity to synthesize tetraenes from C20:3(8,11,14) suggests a significant transition in the activity of the delta 5-desaturase during the last half of gestation. These observations indicate that in liver and brain the capability to chain elongate-desaturate C18:2(9,12) to longer chain homologues increases significantly during early development as a function of transitions in the activity of the delta 5-desaturase.


2001 ◽  
Vol 2001 ◽  
pp. 71-71
Author(s):  
M. Kouba ◽  
M. Enser ◽  
G.R. Nute ◽  
F.M. Whittington ◽  
J.D. Wood ◽  
...  

The n-3 polyunsaturated fatty acids (PUFA) are healthy nutrients which can be increased in pork by feeding sources such as linseed to the growing animal. The levels achieved depend on many factors such as the concentrations of lipid classes in tissues (eg phospholipids containing high PUFA levels are more abundant in muscle than adipose tissue) competition for incorporation with n-6 PUFA and possible inhibitory effects of PUFA on synthesis of saturated and monounsaturated fatty acids. This study examined the time course of the incorporation of n-3 PUFA into tissue lipids and the effects on the major synthetic enzyme D9-desaturase. The effects on pork odour were also studied.


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