PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Medium-Chain Fatty Acids”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources

Inhibitory action of fatty acids on the growth of Neisseria gonorrhoeae.

Fatty acids of various chain lengths (C(1) to C(24)) were examined for their effects on growth, oxygen consumption, and in vitro reduced nicotinamide adenine dinucleotide oxidase activity of Neisseria gonorrhoeae CS-7. The growth inhibition caused by saturated fatty acids increased with increasing chain length to a maximum with palmitic acid (C(16)). Stearic acid (C(18)) and longer saturated fatty acids showed little inhibition of growth. However, unsaturated fatty acids of chain length C(16) to C(20) were inhibitory. Similar inhibition was observed with Bacillus subtilis and a deep rough mutant of Salmonella typhimurium. Wildtype S. typhimurium and Pseudomonas aeruginosa were more resistant to medium-chain (C(7) to C(10)) fatty acids and completely resistant to long-chain (C(12) to C(18)) fatty acids. Thus, sensitivity of N. gonorrhoeae to long-chain fatty acids appears to be related to the permeability of the outer membrane. Growth inhibition by short-chain (C(1) to C(6)) fatty acids was pH dependent; inhibition of growth increased with decreasing pH. Saturated fatty acids inhibited oxygen consumption by log-phase cells of N. gonorrhoeae. This inhibition increased with increasing chain length to a maximum observed with myristic acid (C(14)). Whereas stearic acid (C(18)) had little effect upon oxygen consumption, unsaturated C(18) fatty acids were inhibitory. An in vitro inhibition of reduced nicotinamide adenine dinucleotide oxidase activity by saturated (C(1) to C(12)) and unsaturated (C(16) to C(20)) fatty acids was also observed. Although the inhibitory concentrations were generally higher than those required to inhibit growth or oxygen consumption, an inhibition of electron transport may be partially responsible for the observed growth inhibition.

Bacteria↗

Biochemical and physiologic consequences of carnitine palmityltransferase deficiency.

A patient with a long history of exercise-unduced pain developed myoglobinuria and respiratory failure following extensive exercise (football). Although muscle histochemistry was normal, tissue oxidation of 14C-labeled palmitate was decreased, and muscle carnitine palmityltransferase (CPT) activity was one-tenth of normal. During fasting, his creatine kinase (CK) rose from 127 mu/ml to 278 mu/ml and blood ketones failed to exhibit a normal rise. Triglycerides were normal, as was fatty-acid mobilization. Prolonged exercise resulted in an inordinately increased CK with only moderate elevations in lactate. Treatment with medium-chain triglycerides did not alter his symptoms or improve exercise performance. Pain on exercise is a common complaint, but the occurrence of myoglobinuria points to a defect of energy metabolism; Screening for defects of fat utilization may be accomplished by the prolonged-exercise test, invitro oxidation of 14C-labeled substrates, and prolonged fasting.

Acyltransferases↗

Aspects of long-chain acyl-COA metabolism.

1. Long-chain acid: CoA ligase (AMP-forming) (trivial name acyl-CoA synthetase; EC 6.2.1.3) is located at the membranes of the endoplasmic reticulum and the outer membrane of the mitochondria. The latter membrane has by far the highest specific activity. 2. GTP-dependent synthesis of acyl-CoA has a very low activity in liver mitochondria (about 5% of the activity measured with ATP). CTP, ITP, UTP and GTP may all provide energy for fatty acid activation in sonicated mitochondria by formation of ATP from endogenous ADP and AMP. 3. In rat liver palmitoyl-CoA: L-carnitine O-palmitoyltransferase (trivial name carnitine palmitoyltransferase; EC 2.3.1.21) is located at the microsomal membranes and in the inner membrane of the mitochondria. Its activity is increased, in both membranes, during fasting and in thyroxine-treated rats. The extramitochondrial carnitine palmitoyltransferase may capture part of the acyl CoA formed at the endoplasmic reticulum as acyl-carnitine, especially during fasting and other metabolic conditions of high fatty acid turnover. This transport form of activated fatty acid can penetrate the inner mitochondrial membrane (the acyl-CoA barrier) where it can be reconverted to acyl-CoA, providing the substrate for beta-oxidation in the inner membrane-matrix compartment. The small part of the mitochondrial carnitine palmitoyltransferase, described to be present at the external surface of the mitochondrial inner membrane, may have the same function in the transport of acyl-CoA formed at the mitochondrial outer membrane. 4. Isolated rat liver mitochondria can oxidize high concentrations of palmitate or oleate in the absence of carnitine. In this case the fatty acids are activated in the inner membrane-matrix compartment of the mitochondria, probably by a medium-chain acyl-CoA synthetase with wide substrate specificity. Because this enzyme is less active in heart and absent in skeletal muscle, these tissues oxidize long-chain fatty acids in an obligatory carnitine-dependent fashion. Also the liver oxidizes long-chain fatty acids in a carnitine-dependent way if lower fatty acid concentrations are used. In this tissue carnitine stimulates specifically the partial oxidation of fatty acids to beta-hydroxybutyrate and acetoacetate. 5. The activities of acyl-CoA: sn-glycerol-3-phosphate O-acyltransferase (trivial name glycerophosphate acyltransferase; EC 2.3.1.15) and carnitine palmitoyltransferase change in opposite directions during fasting. These activity changes, together with the measured kinetic properties of the enzymes in mitochondria and microsomes, allow a switch (relatively) from lipid synthesis to ketogenesis during fasting. This switch may occur at the level of long-chain acyl-CoA both in the endoplasmic reticulum and in the mitochondria.

Acyltransferases↗

Lipidomic Profiling Reveals Differential Behaviors of Individual Free Fatty Acids During Altered Metabolic States in Rats.

We used lipidomic analyses to investigate how individual free fatty acids (FFAs) behave differently in metabolic states altered by diet and by antibiotic treatment (ABX) that depletes gut bacteria. Wistar rats were fed either a low-fat or high-fat purified diet, or standard chow with or without antibiotics for two weeks (n = 8-10). Blood samples were then collected before and after meals. Individual FFAs were quantified and grouped based on distinct postprandial response patterns across dietary and treatment conditions. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), key ω-3 FFAs, exhibited postprandial shifts suggestive of suppressed adipocyte lipolysis following meals. Fatty acids in the high-fat diet (HFD) elevated postprandial FFA levels, masking the meal-induced suppression of lipolysis observed with chow or low-fat diet (LFD). Some FFAs, including medium-chain saturated species, remained unaffected by meals. We further evaluated the impact of diet and ABX on baseline (pre-meal) concentrations of FFAs. Certain FFAs were altered by purified diets compared to standard chow. Notably, EPA and DHA were selectively depleted under HFD conditions, likely due to enhanced catabolic activity. In conclusion, lipidomic profiling revealed divergent behaviors among individual FFAs, reflecting distinct metabolic processes and regulatory mechanisms under altered metabolic states.

Animals↗

Transport of long-chain fatty acids by Escherichia coli: mapping and characterization of mutants in the fadL gene.

A new locus (fadL) that is required for the utilization of long-chain fatty acids has been mapped and partially characterized in an Escherichia coli mutant. The fadL locus has been mapped at 50 min on the chromosome. A mutant bearing a defect in this locus cannot utilize long-chain fatty acids as a sole carbon source. Derivatives of this mutant that can grow on decanoate (termed fadR) are capable of growth on medium-chain but not long-chain fatty acids. It is believed that the fadL mutants is defective in the transport of long-chain fatty acids into the cell for the following reasons: (i) fadR fadL strains can oxidize in vivo decanoate but not oleate; (ii) neither fadL nor fadR fadL strains can incorporate oleate into their membrane lipids; (iii) the activity of the acyl-CoA synthetase (EC 6.2.1.3) in fadR fadL strains is comparable to the acyl-CoA synthetase activity in fadR fadL+ strains; and (iv) in vitro extracts from fadR fadL+ strains. If the above hypothesis is correct, the uptake of long-chain fatty acids by E. coli requires at least two gene products.

Biological Transport↗

Ethylmalonic-adipic aciduria. In vivo and in vitro studies indicating deficiency of activities of multiple acyl-CoA dehydrogenases.

The mechanisms underlying ethylmalonic-adipic aciduria were studied in a 5-yr-old girl. Oxidation of radioactive substrates by cultured skin fibroblasts from the proband and asymptomatic family members was also determined and compared to that by normal fibroblasts and that by cells from a patient with glutaric aciduria type II. Feeding medium-chain triglycerides promptly induced vomiting and lethargy accompanied by a pronounced increase of urinary ethylmalonate. Significant increases of serum isovalerate and urinary isovalerylglycine were observed after leucine feeding, but urinary glutarate increased only slightly after lysine feeding. Thus, the results from clinical investigation remained equivocal as to whether pathways other than fatty acid oxidation were blocked in our patient. Oxidation of [1-(14)C]butyrate by cultured skin fibroblasts from the proband was reduced to 14% of control. In vitro oxidation of [2-(14)C]lysine and [2-(14)C]leucine was also reduced to 28 and 23% of control, respectively. Much more severe reduction in oxidation of these three substrates (3, 9, and 9%, respectively) was observed in glutaric aciduria type II cells. These results indicated that in the proband, degradative pathways of fatty acids, lysine, and leucine are blocked at the steps of butyryl-CoA, glutaryl-CoA, and isovaleryl-CoA dehydrogenases, respectively, as in the case of glutaric aciduria type II. Because activities of multiple acyl-CoA dehydrogenases are reduced, a deficiency of electron-transferring flavoprotein, which serves as a hydrogen-acceptor for these dehydrogenases, is postulated as the underlying mechanisms of these two diseases, but a genetic heterogeneity was indicated by significant differences in the residual activities in these two types of cells. The hypothesis of more than one mutant allele of an autosomal recessive gene was also suggested by the study on cells from asymptomatic members of the family.

Acidosis↗

Thiolases of Escherichia coli: purification and chain length specificities.

The presence of only one thiolase (EC 2.3.1.9) in wild-type Escherichia coli induced for enzymes of beta oxidation was demonstrated. A different thiolase was shown to be present in a mutant constitutive for the enzymes of butyrate degradation. The two thiolases were purified to near homogeneity by a simple two-step procedure and were found to be associated with different proteins as shown by gel electrophoresis. The thiolase isolated from induced wild-type Escherichia coli cell was active on beta-ketoacyl-coenzyme A derivatives containing 4 to 16 carbons, but exhibited optimal activity with medium-chain substrates. In contrast, the thiolase isolated from the constitutive mutant was shown to be specific for acetoacetyl-coenzyme A.

Acetyl-CoA C-Acetyltransferase↗

Fatty liver, encephalopathy, and sudden unexpected death in early childhood due to medium-chain acyl-coenzyme A dehydrogenase deficiency.

A case of sudden death associated with fatty liver and encephalopathy is described in a 4-year old white boy with medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency. The death was caused by hypoglycemia triggered by fasting and vomiting associated with a minor viral infection. The differential diagnosis of the hepatoencephalopathy is discussed in relation to other conditions, especially Reye's syndrome. The forensic pathologist should be familiar with MCAD and other deficiencies of beta-oxidation of fatty acids as a cause of sudden unexpected death in children in order to advise parents in genetic counseling to prevent disability or death of other affected, but still asymptomatic siblings.

Brain Diseases↗

Long-term effect of medium-chain triglyceride on hepatic enzymes catalyzing lipogenesis and cholesterogenesis in rats.

This study was conducted to investigate the long-term effect of dietary medium-chain triglyceride (MCT) as compared with that of corn oil feeding on lipid metabolism in rats. Both serum cholesterol and triglyceride levels in MCT-fed rats showed significant decrease during the experimental period of eight weeks, although liver cholesterol and triglyceride contents were not distinguishable between the two groups. Significant elevation of the activity of lipogenic enzymes, such as fatty acid synthetase (FAS) and malic enzyme (ME) of the liver, was observed in MCT-fed rats without any fat accumulation of the liver (fatty liver). The increase of lipogenic enzyme activity was accompanied by a significant reduction of essential fatty acids (EFA) such as 18:2 (omega6) and 20:4 (omega6) in total liver lipid. In contrast, hepatic beta-hydroxy-beta-methylglutaryl CoA(HMG-CoA) reductase activity was significantly decreased in MCT-fed rats, that would play an important role in achieving hypocholesterolemia. From these results obtained in a long-term experiment, it is concluded that exogenous MCT depresses the key enzyme catalyzing cholesterol synthesis with a concomitant elevation of lipogenic enzyme activity in the rat liver.

Animals↗

Acyl-CoA synthetases in guinea-pig liver mitochondria. Purification and characterization of a distinct propionyl-CoA synthetase.

Guinea-pig liver mitochondria contain three soluble ATP-dependent acyl-CoA synthetases: (a) a medium-chain acyl-CoA synthetase, (b) a salicylate activating enzyme, and (c) a propionyl-CoA synthetase. A complete separation of these enzymes has been accomplished and the resulting preparation of propionyl-CoA synthetase (Spec. act. 4 units/mg protein) accepts acetate, propionate and butyrate as substrates with a high preference for propionate.

Acetates↗

Medium-chain triglyceride feeding in premature infants: effects on calcium and magnesium absorption.

The effect of medium-chain triglycerides (MCT) on the absorption of calcium and magnesium in premature infants was studied in 34 infants with birth weights lower than 2,000 gm. The infants were divided into three groups and fed three formulas similar in nutrient content except for the type of fat, as follows: group 1 (control): corn oil, oleo, and coconut oil (39:41:20); group 2: MCT, corn oil, and coconut oil (40:40:20); group 3: MCT and corn oil (80:20). The infants fed MCT-containing formulas absorbed significantly more calcium than the control group. Magnesium absorption was significantly increased in the 80% MCT group.

Absorption↗

Medium-chain triglyceride feeding in premature infants: effects on fat and nitrogen absorption.

The effect of medium-chain triglycerides (MCT) on the "physiological" steatorrhea of prematurity was studied in 34 infants with birthweights below 2,000 gm. The infants were divided into three groups and fed three formulas identical in nutrient content except for the type of fat, as follows: group 1 (control): corn oil, oleo, and coconut oil (39:41:20); group 2: MCT, corn oil, and coconut oil (40:40:20); group 3: MCT and corn oil (80:20). The infants fed MCT-containing formulas had striking diminution in stool volume and frequency. Their total fat absorption was significantly improved when compared with controls; nitrogen absorption was slightly but significantly improved in the 80% MCT group. The results also suggest that nitrogen sparing may be enhanced in premature infants fed MCT-containing formulas.

Birth Weight↗

Iron-Deprivation Liposomes for Cancer Therapy.

Targeting iron homeostasis in tumor cells represents a promising anticancer strategy, as iron plays essential roles in tumor growth, invasion, and metastasis. Although deferoxamine can effectively chelate iron, its clinical application is limited by poor membrane permeability, short half-life, and lack of targeting capability. To overcome these challenges, we designed and synthesized a family of DFO-bearing lipids by modifying the molecule with dual fatty acid chains of varying lengths, and co-assembled them with auxiliary lipids via microfluidics to construct "iron-deprivation" liposomes. Among them, the medium-chain DFO-C12-liposomes exhibited the highest cellular uptake, iron-deprivation efficiency, and anticancer activity in vitro, markedly depleting mitochondrial iron, disrupting Fe-S cluster synthesis, suppressing mitochondrial respiration, and inducing autophagy. Furthermore, DFO-C12-liposomes efficiently coordinated Mn2 + via DFO-Mn2 + chelation, providing MRI capability while inducing iron deprivation-mediated ferroptosis. In addition, the iron-deprivation liposomes can encapsulate anticancer drugs such as doxorubicin, leading to an enhanced antitumor effect through the combination of iron deprivation and chemotherapy for osteosarcoma treatment. In summary, the "iron-deprivation" liposomes integrate iron chelation, imaging functionality, and chain-length-dependent cellular uptake into a versatile nanoplatform for regulating tumor iron homeostasis and achieving enhanced antitumor efficacy through multimodal therapeutic strategies.

alkyl chain‐length engineering↗

A disorder of muscle lipid metabolism and myoglobinuria. Absence of carnitine palmityl transferase.

Two brothers, 29 and 33 years of age, had recurrent myoglobinuria, renal failure and azotemia, but were otherwise normal, without apparent muscle weakness or exercise intolerance. Ischemic exercise resulted in normal lactate production. Muscle glycogen content and activities of phosphorylase and phosphofructokinase were normal. Plasma triglycerides were elevated (500 mg per deciliter) on a regular diet and rose during fasting. During a 72-hour fast, serum creatine phosphokinase rose more than 10 times, and myoglobin was detected in urine. Plasma ketone production was minimal during fasting, but prompt ketonemia ( a normal response) occurred after ingestion of medium-chain triglycerides. Carnitine palmityl transferase activity was virtually absent in crude muscle extracts and mitochondrial fractions. Lack of this enzyme impairs long-chain fatty acid utilization, reflected in increased content of plasma free fatty acids and plasma triglycerides. Depletion of ATP because of this metabolic block in muscle may account for the attacks of myoglobinuria.

Acute Kidney Injury↗

Necessity of vitamin B12 for growth of rats fed on an odd- or even-carbon-number fat.

1. The effect of vitamin B12 on growth was studied in young male and female rats fed on diets sufficient (+B12) or deficient (-B12) in vitamin B12 containing 30% of the dietary energy as fat, either maize oil (CO) or triundecanoin (TUD). 2. Vitamin B12 deficiency severely depressed growth. After 6 weeks the weight gain of CO(-B12) rats was only 72% of that of CO(+B12) rats and the gain of TUD(-B12) rats was only 47% of TUD(+B12) rats. 3. After fasting 24 or 96 h TUD-fed rats, both +B12 and -B12, had greater glycogen reserves and higher plasma glucose levels than CO-fed rats. 4. It is concluded that vitamin B12 is required for the metabolism and utilization of both an odd-carbon-number medium-chain fat, TUD, and an even-C-number long-chain fat, CO, during growth in rats.

Animals↗

On the mechanism of malonyl-CoA-independent fatty-acid synthesis. Different properties of the mitochondrial chain elongation and enoylCoA reductase in various tissues.

1. NADPH-specific mitochondrial enoyl-CoA reductase can be assayed by a sensitive radioactive test, employing tritium-labelled NADPH, synthesized in a prefixed reaction from D-[1-3H]-glucose via the hexokinase and glucose-6-phosphate dehydrogenase reactions. 2. Liver, kidney cortex, heart muscle, skeletal muscle, brown adipose tissue, brain cortex, and aortic intimal tissue are investigated concerning chain lengths specificity of the chain elongation and the enoyl-CoA reductase. Medium-chain acyl-CoA compounds prove to be the best primers for the chain elongation. Enoyl-CoA reductases still show large incorporation rates with hexadecenoyl-CoA. 3. The differences in the chain lengths specificity of the chain elongation and enoyl-CoA reductase can be explained by the inhibitory effect of long-chain acyl-CoA derivatives on the 3-hydroxyacyl-CoA dehydrogenase. 4. The nucleotide specificity in the different tissues reveals two types of chain elongation: In addition to liver and kidney cortex, mitochondria of brown adipose tissue need NADH + NADPH for optimal chain elongation, whereas heart muscle, skeletal muscle and aortic intimal mitochondria only need NADH. 5. Different physiological roles are proposed for the two types. The "heart type" may be of importance in the conservation of reducing equivalents or acetate units in the anaerobic state, the "liver type" may play a role in the transfer of hydrogen from NADPH to the respiratory chain. In addition, the mitochondrial chain elongation may serve as bypass of the first part of the respiratory chain.

Adipose Tissue, Brown↗

Free fatty acid and glucose metabolism during hypothermic perfusion of canine kidneys.

Canine kidneys were subjected to continuous nonpulsatile perfusion using 200 ml of a perfusate containing 50 g/l albumin. When optimal oxygenation was achieved, perfusate K+ contents were unchanged for 24 h, indicating adequate membrane function but tended to increase thereafter. Lowered oxygen pressures resulted in significant cellular K+ loss during the first hours of perfusion. During oxygenated perfusion, glucose and free fatty acids (FFA) were oxidized in considerable amounts with a preferential consumption of octanoate. A capacity for long-chain FFA oxidation became obvious when the octanoate had been used up, but the amount of these FFA in the perfusate depended preferentially on FFA being liberated from tissue lipids during the 1st day of perfusion. Glucose consumption rates were highest during the first 2 days of perfusion but the subsequent reduction of the metabolic rate was not accompanied by an accumulation of lactate. Thus medium-chain FFA and glucose should be supplied to the continuously perfused kidney in hypothermia and optimal oxygenation of the perfusate should be guaranteed. However, it seems to be unnecessary to supply exogenous long-chain FFA.

Albumins↗