Fatty acid synthesis in mitochondria elongation of short-chain fatty acids and formation of unsaturated long-chain fatty acids

Author(s):  
E.J.V.J. Christ
1972 ◽  
Vol 129 (4) ◽  
pp. 929-935 ◽  
Author(s):  
Isabel A. Forsyth ◽  
Christopher R. Strong ◽  
Raymond Dils

1. The rate of fatty acid synthesis by mammary explants from rabbits pregnant for 16 days or from rabbits pseudopregnant for 11 days was stimulated up to 15-fold by culturing for 2–4 days with prolactin. This treatment initiated the predominant synthesis of C8:0 and C10:0 fatty acids, which are characteristic of rabbit milk. 2. Inclusion of insulin in the culture medium increased the rate of synthesis of these medium-chain fatty acids. By contrast the inclusion of corticosterone led to the predominant synthesis of long-chain fatty acids. When explants were cultured for 2–4 days with insulin, corticosterone and prolactin, the rate of fatty acid synthesis increased up to 42-fold, but both medium- and long-chain fatty acids were synthesized. 3. These results show that the stimulus to mammary-gland lipogenesis and the initiation of synthesis of medium-chain fatty acids observed between days 16 and 23 of pregnancy in the rabbit can be simulated in vitro by prolactin alone. 4. When mammary explants from rabbits pregnant for 23 days were cultured for 2 days with insulin, corticosterone and prolactin, the rate of fatty acid synthesis increased fivefold, but there was a preferential synthesis of long-chain fatty acids. Culture with prolactin alone had little effect on the rate or pattern of fatty acids synthesized. 5. The results are compared with findings in vivo on the control of lipogenesis in the rabbit mammary gland, and are contrasted with the known effects of hormones in vitro on the mammary gland of the mid-pregnant mouse.


2006 ◽  
Vol 290 (3) ◽  
pp. C785-C792 ◽  
Author(s):  
Gavin Stewart ◽  
Tohru Hira ◽  
Andrew Higgins ◽  
Craig P. Smith ◽  
John T. McLaughlin

Several orphan G protein-coupled receptors, including GPR40, have recently been shown to be responsive to fatty acids. Although previous reports have suggested GPR40 detects medium- and long-chain fatty acids, it has been reported to be unresponsive to short chain fatty acids. In this study, we have heterologously expressed mouse GPR40 in Xenopus laevis oocytes and measured fatty acid-induced increases in intracellular Ca2+, via two electrode voltage clamp recordings of the endogenous Ca2+-activated chloride conductance. Exposure to 500 μM linoleic acid (C18:2), a long-chain fatty acid, stimulated significant currents in mGPR40-injected oocytes ( P < 0.01, ANOVA), but not in water-injected control oocytes (not significant, ANOVA). These currents were confirmed as Ca2+-activated chloride conductances because they were biphasic, sensitive to changes in external pH, and inhibited by DIDS. Similar currents were observed with medium-chain fatty acids, such as lauric acid (C12:0) ( P < 0.01, ANOVA), and more importantly, with short-chain fatty acids, such as butyric acid (C4:0) ( P < 0.01, ANOVA). In contrast, no responses were observed in mGPR40-injected oocytes exposed to either acetic acid (C2:0) or propionic acid (C3:0). Therefore, GPR40 has the capacity to respond to fatty acids with chain lengths of four or greater. This finding has important implications for understanding the structure:function relationship of fatty acid sensors, and potentially for short-chain fatty acid sensing in the gastrointestinal tract.


1958 ◽  
Vol 149 (936) ◽  
pp. 414-420

1. Introduction: The role of acetate in fatty-acid synthesis In 1945 Folley and his colleagues (see Foiley 1949, 1952; Malpress 1946) suggested that, in the ruminant, short-chain fatty acids might be synthesized by the lactating mammary gland from acetate. These short-chain fatty acids might then serve as precursors for the synthesis of long-chain acids. Folley & French (1949, 1950) showed that in vitro slices of lactating ruminant mammary gland were able to synthesize fat from acetate, as indicated by a respiratory quotient greater than unity. Non-ruminant lactating mammary tissue was unable to do so, but could utilize glucose for fat synthesis. It was later shown, with the aid of tracers (Balmain, Folley & Glascock 1954) that non-ruminant lactating mammary gland slices could use acetate for the synthesis of fat, provided that glucose was also added. Experiments in vivo laid emphasis upon the synthesis of short-chain fatty acids by the mammary gland. Popják & Beeckmans (1950) showed that injection of [ carboxy - 14 C]acetate into the pregnant rabbit gave rise to a high degree of labelling in the mammary gland fat. Fractionation of these fatty acids (Popják, Folley & French 1950) showed that the label was predominantly concentrated in the short-chain fatty acids, and that this labelling was far higher than that found in the liver fatty acids, indicating synthesis in the gland itself.


1998 ◽  
Vol 53 (11-12) ◽  
pp. 995-1003 ◽  

Abstract Herbicidal chloroacetamides cause a very sensitive inhibition of fatty acid incorporation into an insoluble cell wall fraction of Scenedesmus acutus. The molecular basis was investigated in more detail. After incubation of the algae with [14C]oleic acid and saponification, the remaining pellet was solubilized and fractionated consecutively with chloroform / methanol, phosphate buffer, amylase, pronase, and finally with dioxane/HCl. By acid hydrolysis in dioxane a part of the cell wall residue was solubilized showing inhibition of exogenously applied oleic acid and other labelled precursors such as stearic acid, palmitic acid, and acetate. After extraction of this dioxane-soluble subfraction with hexane, HPLC could separate labelled metabolites less polar than oleic acid. T heir formation was completely inhibited by chloroacetam ides, e.g. 1 μᴍ metazachlor. This effect was also observed with the herbicidally active 5-enantiomer of metolachlor while the inactive R-enantiomer had no influence. These strongly inhibited metabolites could be characterized by radio-HPLC /MS as very long chain fatty acids (VLCFAs) with a carbon chain between 20 and 26. Incubating am etazachlor-resistant cell line of S. acutus (Mz-1) with [14C]oleic acid, V LCFA s could not be detected in the dioxane/ HCl-subfraction. Furthermore, comparing the presence of endogenous fatty acids in wildtype and mutant Mz-1 the VLCFA content of the mutant is very low, while the content of long chain fatty acids (C16 -18) is increased, particularly oleic acid. Obviously, the phytotoxicity of chloroacetam ides in S. acutus is due to inhibition of VLCFA synthesis. The resistance of the mutant to metazachlor has a bearing on the higher amount of long chain fatty acids replacing the missing VLCFAs in essential membranes or cell wall components.


2004 ◽  
Vol 381 (3) ◽  
pp. 941-949 ◽  
Author(s):  
Roger SCHNEITER ◽  
Britta BRÜGGER ◽  
Clare M. AMANN ◽  
Glenn D. PRESTWICH ◽  
Raquel F. EPAND ◽  
...  

Morphological analysis of a conditional yeast mutant in acetyl-CoA carboxylase acc1ts/mtr7, the rate-limiting enzyme of fatty acid synthesis, suggested that the synthesis of C26 VLCFAs (very-long-chain fatty acids) is important for maintaining the structure and function of the nuclear membrane. To characterize this C26-dependent pathway in more detail, we have now examined cells that are blocked in pathways that require C26. In yeast, ceramide synthesis and remodelling of GPI (glycosylphosphatidylinositol)-anchors are two pathways that incorporate C26 into lipids. Conditional mutants blocked in either ceramide synthesis or the synthesis of GPI anchors do not display the characteristic alterations of the nuclear envelope observed in acc1ts, indicating that the synthesis of another C26-containing lipid may be affected in acc1ts mutant cells. Lipid analysis of isolated nuclear membranes revealed the presence of a novel C26-substituted PI (phosphatidylinositol). This C26-PI accounts for approx. 1% of all the PI species, and is present in both the nuclear and the plasma membrane. Remarkably, this C26-PI is the only C26-containing glycerophospholipid that is detectable in wild-type yeast, and the C26-substitution is highly specific for the sn-1 position of the glycerol backbone. To characterize the biophysical properties of this lipid, it was chemically synthesized. In contrast to PIs with normal long-chain fatty acids (C16 or C18), the C26-PI greatly reduced the bilayer to hexagonal phase transition of liposomes composed of 1,2-dielaidoyl-sn-glycero-3-phosphoethanolamine (DEPE). The biophysical properties of this lipid are thus consistent with a possible role in stabilizing highly curved membrane domains.


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