Acetylcarnitine and Free Carnitine in Body Fluids before and after Birth

Abstract

SummaryThe acetylcarnitine concentration in amniotic fluid fell significantly between 33 and 37 and 40 weeks of gestation. It was significantly higher in samples that had a low lecithin to sphingomyelin ratio. The acetylcarnitine content of tracheal fluid was higher in samples obtained from premature newborns. The major excretory form of carnitine is the acetate ester and only in adults does the urine contain significant amounts of free carnitine. The level of acetylcarnitine in plasma significantly increases after the first day of life; there was no difference in the plasma levels of carnitine between full-term and premature newborns. Plasma-free carnitine and acetylcarnitine levels were significantly lower in infants who were receiving a soybean-based formula. A positive correlation was found between the plasma level of ketone bodies and that of acetylcarnitine. SpeculationA characteristic of early postnatal adaptation in human newborns is a high dependence on the utilization of fatty acids derived from endogenous sources and increasingly from digested milk triglycerides. This essential energy-producing mechanism seems to be facilitated by carnitine, of which a considerable amount is derived from m a .It is well known that the change from fetal life to extrauterine existence entails, among other things, changes in the supply and utilization of nutriknts. In mammals, including humans, the "prenatal diet" can be considered as one high in carbohydrate, postnatally as a high-fat diet (1, 18). This change is accompanied by a rapid m e in blood levels of free fatty acids and ketone bodies after birth (26,28,38). This rapid elevation of free fatty acid blood levels in human newborns during or shortly after birth is due to the release of fatty acids from adipose tissue mainly in response to j? adrenergic stimulation of lipolysis (29,39). Later high levels of free fatty acid in blood reflect intestinal absorption of fatty acids from triglycerides supplied in the diet (18). Thus, / 3 oxidation of free fatty acid would seem to be a very important source of energy in the newborn. Carnitine (y-trimethylamino-P-hydroxybutyrate) is essential for optimum oxidation of fatty acids in mitochondria (2), since it facilitates transport of fatty acid across the mitochondrial membrane:There is no doubt that carnitine and the carnitine transferases are essential for fatty acid oxidation after birth. We have reported relatively constant individual levels of free carnitine after birth in whole blood (35). However, there is substantial carnitine excretion in urine (35) before onset of feeding. Intake of exogenous carnitine 1 varies with the type of milk fed. Formulas with a soybean base have no detectable carnitine (35).The rapid postnatal increase in fat utilization in the rat is accompanied by a rise in hepatic (2, 3), cardiac (42, 43), brain (19), and brown fat (19) carnitine palmitoyl transferase and carnitine acetyl transferase activities. In man, carnitine palmitoyl transferase activity in white fat also rises rapidly after birth (...

Neonatal Blood Carnitine Concentrations: Normative Data by Electrospray Tandem Mass Spectometry

“…There is no agreement in the literature regarding the concentration of fetal blood carnitine with advancing gestation. Some reports show a significant decrease of fetal blood carnitine levels in the later stages of gestation (16,17,20,21,23), whereas others have shown no changes in fetal blood carnitine levels during gestation (24,26). These observations have been made in newborns delivered prematurely and may not be an accurate representation of the blood carnitine concentration at that respective age of gestation under healthy conditions.…”

“…This ratio is often abnormal in inborn errors of metabolism such as fatty acid oxidation deficiencies, other mitochondrial disorders, and organic acidurias (1,13,14). The high AC/FC ratio noted in neonates is thought to reflect the increased production of acyl-CoA derivatives, mainly acetylCoA, produced by the normally enhanced fatty acid oxidation in the newborn period (3,5,6,19,26) when the neonate is first exposed to fasting.…”

“…First, the number of newborns studied was much smaller than in our study and thus more prone to sample size biases. Second, several studies have shown changes in TC, FC, and AC within the first days of life (3,9,11,16,19,21,24,26,33). Therefore, timing of blood sampling (day of life 1.85 versus day of life 5) might explain some differences in the reported carnitine concentrations.…”

“…Only a few articles (3, 11, 16 -25) have reported carnitine concentrations in the perinatal period since the original report of Novack et al (26). However the interpretation of the cumulative information from these reports is difficult because of several differences: 1) the study populations 2), technical methods 3), postnatal timing of samples, and 4) analyzed tissues (e.g.…”

Enterohepatic Distribution of Carnitine in Developing Piglets: Relation to Glucagon and Insulin

“…As such, carnitine insufficiency has been shown to impair lipid utilization in premature newborns (6,7). The human newborn is especially susceptible to develop carnitine insufficiency because of low levels in premature infants (8), inadequate dietary intake of carnitine (9), and insufficient endogenous synthesis (10).…”