Carnitine carbon is derived metabolically from lysine and methionine in animals The primary biosynthetic site is the liver, although butyrobetaine hydroxylase, the key enzyme catalyzing the final step in carnitine biosynthesis, is found in liver, kidney, and brain 2. The fetus is incapable of endogenous synthesis of carnitine due to the lack of this enzyme Recently, butyrobetaine hydroxylase activity has been detected in fetal-placental tissues 16 , but the activity is low.
Thus, carnitine concentrations in fetal tissues are greatly dependent on maternal carnitine status and the rate of placental transfer 15 , Carnitine deficiency develops among very low birth weight infants who do not receive exogenous carnitine supplementation Therefore, adequate supply of exogenous carnitine may be important for fetal growth and organ development, especially for fetuses having potential genetic defects related to long-chain fatty acid oxidative metabolism.
Supplementation with L-carnitine may improve fetal energy metabolism by increasing carnitine level, subsequently altering the acetyl-CoA:CoA ratio, metabolic pathways, and energy supply.
Carnitine was shown to modulate the expression and activity of placental short-chain 3-hydroxyacyl CoA dehydrogenase, one of the mitochondrial fatty acid oxidation enzymes 4.
Furthermore, L-carnitine supplementation stimulated CPT I and subsequently accelerated palmitate oxidation in newborn piglets during cardiac development and hypoxia In addition to stimulating CPT activity and increasing fatty acid oxidation, supplementation with L-carnitine was shown to stimulate pyruvate dehydrogenase complex PDHC activity in isolated human skeletal muscle mitochondria 22 , 23 and increase glucose oxidation in the fatty acid-perfused isolated working heart Correspondingly, increases in oxidative capacity could improve mitochondrial bioenergetics and aid development of fetuses at risk for prematurity and intrauterine growth retardation.
We have examined this hypothesis by testing the effects of maternal supplementation with carnitine on carnitine status and CPT and PDHC activities in liver, kidney, and heart tissues from and d-old pig fetuses, the stage at which fetal weight and protein accretion are accelerated Pregnant, first-parity swine average body weight The pigs consumed diets and water ad libitum.
On d 55 and 70, the pigs were killed by electrical stunning followed by exsanguination. A mid-lateral incision was made to gain access to the abdominal cavity. The ovarian pedicles and uterine stump, at the level of the cranial cervix, were cut and the uterus removed. Once the uterus was removed, fetuses were collected from the right uterine horn under aseptic conditions. Fetal weights averaged Liver, kidney, and heart from each individual fetus were removed and immediately snap-frozen in liquid nitrogen.
Tissue samples were homogenized PRO homogenizer, Pro Scientific in perchloric acid, and free carnitine and acylcarnitines were extracted as described by Lin and Odle Carnitine and acylcarnitine concentrations were determined using an enzymatic radioisotope method 29 , The homogenization was conducted with a ratio of tissue and buffer of g:mL.
Homogenate protein concentration was determined by use of the biuret method Tissue samples were homogenized and protein was determined as described above. PDHC-activated activity was measured in tissue homogenates using a modified method described by Uziel et al. Each flask was sealed with a rubber cap from which a small tube was suspended containing 0.
The reaction was terminated by injecting 0. The 14 CO 2 produced from the reaction was trapped in the center tubes and radioactivity was measured by liquid scintillation counting L-[ N -methyl- 3 H]-carnitine 2. Tissue differences were also evaluated by multivariate ANOVA based on a completely randomized design using the general linear models procedure.
Maternal supplementation with dietary L-carnitine during early pregnancy significantly increased fetal free carnitine and long-chain acylcarnitine concentrations in liver and free carnitine concentration in heart, but did not affect the kidney tissues of fetuses Table 1. Age did not affect carnitine status in fetal heart and kidney tissues. The effects of maternal carnitine supplementation and gestational age on total carnitine status were similar to the effects on free and acylcarnitines.
Supplementation with dietary L-carnitine to dams had no effects on specific activity of CPT malonyl-CoA inhibited and uninhibited in kidney and heart tissue and its kinetic constants in any tissue from or d-old fetuses but was associated with a significant increase in CPT activity Fig. Similar to the carnitine status, CPT activity and kinetic constants differed among the various fetal tissues. The apparent malonyl-CoA—inhibited activity in kidney was 1 times higher than in heart and 4 times higher than in liver.
The uninhibited activity in kidney was similar to the activity in liver but was 1. The K m for carnitine obtained from liver 0. The values of K m for carnitine were significantly higher than free carnitine concentrations in liver and kidney from d-old fetuses and in all of the measured tissues from d-old fetuses with or without maternal dietary carnitine supplementation Fig.
Tissue carnitine concentrations were corrected using tissue dry weight:wet weight ratios The enzyme activity decreased in heart tissue but increased in kidney tissue with gestational age. The enzyme activity in the kidney was greater than in liver and heart.
Previous studies 5 , 33 , 34 demonstrate the placenta-fetal interrelationship in carnitine metabolism during pregnancy and suggest that supplementation of carnitine during pregnancy may be beneficial to both mother and fetus. However, the effect of maternal carnitine supplementation on fetal tissue carnitine status deserves evaluation, given the importance of placental transfer 7. Our results show that dietary supplementation of L-carnitine to pregnant dams significantly increased carnitine concentrations in fetal liver, heart, and muscle tissues 35 , demonstrating that the placenta is capable of increasing the transport of carnitine to the fetus in the early stages of pregnancy.
Results from earlier studies also showed that carnitine placental transfer in humans occurred primarily in the middle stage 33 or the last trimester of pregnancy Our data are consistent with these observations in humans, suggesting that carnitine placental transfer in the porcine species occurs at the same stage of pregnancy in humans.
The patterns of carnitine distribution in fetal tissues also are similar to human neonates Therefore, the data further support the pig as an appropriate animal model for studies concerning perinatal carnitine metabolism. Supplementation with maternal dietary L-carnitine increases placenta carnitine transfer and fetal tissue carnitine deposition, but the uptake of carnitine varies greatly among tissues. Carnitine concentrations were higher in heart than in liver and kidney.
Supplementation with L-carnitine significantly increased carnitine uptake in fetal liver and heart but did not affect kidney. Moreover, the uptake of carnitine was associated with increasing gestational age in liver but not in heart and kidney. In addition, oxidative metabolism is greater in heart than in liver and kidney of fetuses; thus, the carnitine concentrations may reflect the difference in vital functions, such as the rate of oxidative metabolism for the production of energy in the tissues during fetal life 7.
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Considering that several health factors can contribute to a reduced carnitine status during pregnancy, we recommend that all expecting mothers talk to their doctors about whether they are getting enough carnitine, or whether additional carnitine supplementation is needed.
Carnitine: A compound found in animal proteins and synthesized in the human body to help support cellular health and energy production. He holds a Masters Degree in Nutrition, and believes that many health conditions are the result of suboptimal nutrient status.
For this reason, Adin is committed to informing others about the latest research in nutrition, lifestyle modification, and dietary supplements. Several studies seem promising when it comes to L-carnitine use during pregnancy. A study in the "Journal of Animal Physiology and Animal Nutrition" found that supplemental L-carnitine during pregnancy increases insulin-like growth factor levels in the body.
This, in turn, may enhance placenta development and intrauterine nutrition of unborn babies, which theoretically explains the higher birth weights associated with the supplement, notes lead study author J. Supplementing after a baby's birth may also help boost the energy and nutrient value of breast milk, according to a study published in the "Journal of Nutrition.
Women who develop preeclampsia, a pregnancy condition characterized by elevated blood pressure and protein in the urine, have higher than normal blood levels of L-carnitine, according to a "Obstetrics and Gynecology" study. Just what this means in terms of carnitine supplementation during pregnancy remains unclear as of July , so it's better to avoid this supplement during pregnancy until more is known, advises "Pregnancy Do's and Don'ts" author Elisabeth A.
Preeclampsia can cause severe complications when you are pregnant. These include liver rupture, stroke, bleeding problems and premature separation of your placenta from your uterus, though a mother's death due to preeclampsia is rare.
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