Fatty Acid Synthesis by Subcellular Fractions of Lung Tissue

Tombropoulos, Elias G.

doi:10.1126/science.146.3648.1180

Cited by 37 publications

(6 citation statements)

References 6 publications

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“…This data is at variance with that of Tombropolous [19], who reported that mitoclzondrial fatty acid synthesis was the most active pathway in lung. T h e hepatic pattern of relatively low prenatal activity is similar to that described previously [22] in developing rat heart.…”

Section: Discussioncontrasting

confidence: 56%

Enzyme Activities Related to Fatty Acid Synthesis in Developing Mammalian Lung

Gross

Warshaw

1974

Pediatr Res

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ExtractFatty acids are important components of pulmonary surface-active lipids and lung membranes. We have investigated fatty acid synthesis in developing rabbit lung by measuring the rate of incorporation of (14C)acetyl or (14C)malonyl-CoA into pentaneextractable fatty acids. Because the lung can incorporate exogenously supplied as well as endogenously synthesized fatty acid into phospholipid, parallel studies of hepatic fatty acid synthesis were carried out.Fatty acids can be synthesized in fetal rabbit lung by the de nouo pathway and to a lesser extent by chain elongation. The activity of enzymes related to de nouo fatty acid synthesis is at adult levels by 23 days of fetal life and remains fairly constant thereafter. Enzymes associated with hepatic de nouo fatty acid synthesis reach very 'high levels of activity during fetal life but this decreases by 50% after birth, in association with the onset of suckling. Activity of the enzymes of de nouo pulmonary synthesis appears to be unaffected by birth and onset of nutritional intake.Pulmonary and hepatic fatty acid elongation do not appear to be major routes of fatty acid synthesis in the fetal rabbit. Microsomal elongation activity is low in the fetus and on the first day of life, adult activity being fourfold greater. Pulmonary mitochondrial elongation becomes progressively more active during fetal life, but quantitatively appears less important than de nouo synthesis.Gas-liquid chromatography of the fatty acids synthesized by fatty acid synthetase in the supernatant fraction of lung homogenates revealed that the main product was palmitic acid, a major component of dipalmityl lecithin which is an important surfaceactive lipid. The maior products of pulmonary mitochondrial and microsomal fatty acid elongation were stearic acid and 20-and 22-carbon unsaturated fatty acids.The early maturation of the enzymes of the de nouo pathway ensures a source of fatty acid for lung membrane growth and for surfactant formation when the pathways for lecithin synthesis mature. SpeculationInasmuch as the enzymes associated with de nouo fatty acid synthesis are active before the pathway for lecithin synthesis matures, fatty acid synthesis is probably not the ratelimiting factor in surfactant production in the rabbit fetus. The role of other lecithin precursors such as choline remains to be investigated.Early dietary intake does not appear to influence pulmonary fatty acid synthesis, but may play an important role in overall pulmonary lipid metabolism and the regulation of lung surface activity.

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Section: Discussioncontrasting

confidence: 56%

Enzyme Activities Related to Fatty Acid Synthesis in Developing Mammalian Lung

Gross

Warshaw

1974

Pediatr Res

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“…Numerous studies [9,11,18,19,24,27,31,32,34,351 have shown that mammalian lung tissue synthesizes fatty acids and rapidly incorporates radioactive acetate and palmitate into lecithin and other phospholipids, but very little [2, 161 is reported on the de nouo biosynthesis of lecithin in fetal or adult lung.…”

Section: Introductionmentioning

confidence: 99%

The Biochemical Development of Surface Activity in Mammalian Lung: II. The Biosynthesis of Phospholipids in the Lung of the Developing Rabbit Fetus and Newborn

1967

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ExtractIn the lung of the rabbit fetus there was a rise in concentration of total lipids before term, the phospholipids constituting the major fraction. The concentrations of phosphatidylethanolamine and lecithin rose concurrently until day 28 when phosphatidylethanolamine concentration dropped, but lecithin continued to rise to term. From day 28 to term in the nonbreathing fetus there was an increase of 300 % in acetone-precipitated surface-active lecithin found almost entirely in the residual parenchyma after wash with little increase in this fraction in alveolar wash. After breathing for 1 hour there were increases in total alveolar lecithin 3-5 fold over nonbreathing fetal lung while increases in acetoneprecipitated alveolar wash lecithin from nonbreathing to breathing lung were 20-30 fold. Enzymatic reactions were studied in vitro according to the pathways for the de novo synthesis of lecithin and phosphatidylethanolamine as follows:CDP-choline incorporation declined steadily during gestation, although at term still showed rapid incorporation. The methylation reaction (2) showed peak incorporation on day 28 of gestation, at beginning viability. CDP-ethanolamine incorporation was the most active in vitro pathway studied peaking on days 25-26. Serine incorporation showed little activity, following a pattern of incorporation similar to that of CDP-ethanolamine. Activity of all pathways was found in microsomes. Methylation was also found in mitochondria1 fraction of the term fetus and adult and in the cell-free soluble fraction from adult alveolar lavage. Reaction rates were similar from CDP-choline incorporation in both fetal and adult lung homogenate, but fetal lung incorporated methyl groups faster than adult lung. Intermediate compounds of methylation reaction were not found in alveolar wash of fetal lung, but were isolated from adult alveolar wash. Methylation in lung was pH sensitive, peak incorporation was seen at pH 7.8. Addition of ethanol or boiling one minute did not stop methylation. After breathing, those rabbit fetuses delivered by cesarean section after 28 full days of gestation synthesized 100 % of surface-active alveolar lecithin by one hour of breathing, 90 % of incorporation was with 3 H-choline, 10 % with ( 14 CH,)-methionine. Much less incorporation into alveolar wash lecithin was seen with the breathing term fetus, but much more surface-active alveolar wash lecithin was isolated than from the fetus of 28 full days of gestation. SpeculationThe most important pathway in rabbit fetal development and in the newborn rabbit for the de novo synthesis of surface-active alveolar lecithin is the incorporation of CDP-choline. Although there is good correspondence between the concentrations of lecithin and phosphatidylethanolamine in fetal lung and the enzymatic activities studies in vitro, once breathing begins there is little correspondence between in viuo and in vitro biosynthesis of lecithin by fetuses of the same gestational age. In the rabbit fetus and newborn the methylation reaction appears t...

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“…The subcellular site(s) and precise biochemical pathways involved in lung fatty acid synthesis have not been established conclusively. Evidence has appeared suggesting that lung mitochondria are active in surfactant synthesis in general (Klaus et al, 1962) and in fatty acid synthesis in particular (Tombropoulos, 1964). The report ofactive fatty acid synthesis by a mitochondriarich fraction of lung using acetate incorporation into long-chain fatty acids (Tombropoulos, 1964) does not preclude an elongation of existing fatty acyl-CoA derivatives rather than new synthesis.…”

Section: Discussionmentioning

confidence: 99%

Lipid metabolism by rat lung in vitro. Utilization of citrate by normal and starved rats

Scholz

1972

Biochemical Journal

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1. The utilization of [1,5-(14)C(2)]citrate by lung slices and cell cytosol preparations, and the activities of liver and lung cytosol citrate-cleavage enzyme (EC 4.1.3.8), l-malate-NAD oxidoreductase (malate dehydrogenase, EC 1.1.1.37) and phosphoenolpyruvate carboxylase (EC 4.1.1.32) were examined in normal and starved rats. 2. Lipogenesis from citrate was decreased by approx. 70% in both the phospholipid and neutral lipid fractions of lung slices from starved rats as compared with fed controls. 3. Incorporation of citrate by lung cytosol preparations into fatty acids was decreased by approx. 35% in the starved rats. The apparent inhibition by avidin of fatty acid synthesis was overcome partially by preincubation of lung cytosol preparations with biotin. These results are consistent with the presence in lung tissue of the malonyl-CoA pathway for fatty acid synthesis. 4. Lung citrate-cleavage enzyme activity decreased in rats that had been starved for 72h whereas malate dehydrogenase and phosphoenolpyruvate carboxylase activities remained unchanged. The results suggest that the pattern of utilization of lipid precursors by rat lung may be altered during various nutritional states.

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Fatty Acid Synthesis by Subcellular Fractions of Lung Tissue

Cited by 37 publications

References 6 publications

Enzyme Activities Related to Fatty Acid Synthesis in Developing Mammalian Lung

Enzyme Activities Related to Fatty Acid Synthesis in Developing Mammalian Lung

The Biochemical Development of Surface Activity in Mammalian Lung: II. The Biosynthesis of Phospholipids in the Lung of the Developing Rabbit Fetus and Newborn

Lipid metabolism by rat lung in vitro. Utilization of citrate by normal and starved rats

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