No abstract

Extract metabolism. Several follow-ur, studies of infants known t oThe recently developed technique of gas chromatographymass spectrometry supported by computer has considerably improved the analysis of physiologic fluids. This study attempted t o demonstrate the value of this system in the investigation of metabolite patterns in urine in two metabolic problems of prematurity, transient tyrosinemia and late metabolic acidosis. Serial 24-hr urine specimens were analyzed in 9 infants. Transient tyrosinemia, characterized by 5-10-fold increases over basal excretion of tyrosine, p-hydroxyphenyllactate, and p-hydroxyphenylpyruvate in urine, was noted in five of the infants. Several infants had fluctuating levels of tyrosine metabolites in urine although dietary protein intake remained constant a t 3-4 g/kg/24 hr and ascorbic acid at 50 mg/24 hr. Late metabolic acidosis was seen in four infants, but bore n o relation to transient tyrosinemia. The ratio of net acid t o urea excretion in urine increased with increasing base deficit, implying a nonprotein origin of the metabolic acid. No unique metabolic patterns were characteristic of late metabolic acidosis. SpeculationAdvances in gas chromatography-mass spectrometry-computer technology (GC-MS-computer) allow for the screening of body fluids for a wide variety of compounds of biologic importance. One application of this technique is for the investigation of the nutritional adequacy of diets for premature infants. Clinical use of these tools may help establish parameters for assessment of nutrition and allow for a rationalization of diet.There appear to be several defects and disturbances in the metabolism of tyrosine variously grouped under the names tvrosinemia. tvrosinosis. and tyrosyluria (1 7). One such have suffered from transient tyrosinemia could not discern any harmful effects on neurologic or physical development in the first 2 years of life (21, 23). Recently, a long term follow-up study showed that the ultimate intellectual performance, particularly perceptual parameters, may be impaired in some low birth weight infants who had transient tyrosinemia in the neonatal period (22).Late metabolic acidosis (LMA) of the premature, a disturbance of acid-base balance, has been well described in the literature (2, 4,9,13,14,24,(26)(27)(28). We were impressed with several parallels between LMA and transient tyrosinemia. Both occur in prematures at 2-4 weeks of age. Severity and incidence are affected by protein intake and respond favorably t o dietary management. Both are insidious without major symptoms and yet may adversely affect ultimate intellectual outcome.The recently developed technique of GC-MS-computer has made considerable improvements to the tractability and specificity of the chemical analysis of physiologic fluids. It is now possible t o identify and simultaneously quantitate many metabolites and to construct reliable profiles for various groups of compounds so that they might be used t o characterize particular disease states (2, 4 , 9). The technique ha...

c a t h e t e r maintaining the i n t e g r i t y of t h e amniotic cavity and t h e c i r c u l a t i o n . After 2 h r s , 3~/ 1 4~ labeling i n TLC-isolated l e c i t h i n was measured i n various organs. Results (% transported precursor incorporated i n t o l e c i t h i n ) from 4 f e t u s e s LECITHIN SYNTHESIS Lung Liver Brain Kidney Pathway I 82 43 88 70 Pathway I 1 1.7 4.4 5.2 1.3 i n d i c a t e t h a t pathway I predominates over pathway I 1 (phosphat i d y 1 ethanolamine methylation) i n these t i s s u e s . 3~-l e c i t h i n was present i n f e t a l plasma a f t e r 2 h r s but not i n t r a c h e a l o r amniotic f l u i d . Maternal treatment with I M betamethasone 48 h r s p r i o r t o delivery r e s u l t e d i n g r e a t e r than normal incorpor a t i o n of 3~-c h o l i n e i n t o l e c i t h i n i n lung, but not l i v e r , b r a i n , o r kidney i n 2 f e t u s e s examined thus f a r . Additionally, one a c i d o t i c f e t u s showed a reduced pathway I r a t e i n a l l organs except b r a i n . Therefore, t h e choline incorporation pathway of f e t a l primate lung a) i s predominant i n synthesis Regulation of pulmonary l e c i t h i n (the principal surfactantphospholipid) synthesis i s of c r u c i a l importance t o t h e f e t u s and neonate. In our s t u d i e s metabolic control mechanisms have been investigated i n lung samples from over 700 r a t fetuses of varying g e s t a t i o n a l ages. I t has been found by incubation of lung s l i c e s with i s o t o p i c precursors t h a t the choline incorpor a t i o n pathway accounts f o r >97% of l e c i t h i n synthesis. The r a t e of t h i s pathway i s s i g n i f i c a n t l y (p<.001) enhanced a f t e r 20 days g e s t a t i o n (term = 22 days). Specific a c t i v i t i e s of two pathway enzymes, choline kinase (CK) and choline phosphot r a n s f e r a s e (CPT), have been measured i n lung homogenates from r a t f e t u s e s of 16-22 days gestation (DG). CK r i s e s from 740 a t 16.5 DG t o 1440 pmole/min/mg p r o t e i n a t 19.6 DG (p<.001) and f a l l s from t h i s peak value t o 760 pmole/min/mg a t 21.3 DG. CPT, although r i s i n g from 38 pmole/min/mg a t 16.5 DG t o 54 a t 19.6 DG (p<.02), does not peak u n t i l 20.5 DG (60 pmole/min/mg, p<.001). The enzyme then declines i n a c t i v i t y as t h e f e t u s approaches term. Kinetic properties (Km values, pH p r o f i l e s , e t c . ) have a l s o been determined f o r C K and CPT.These findings suggest t h a t C K and CPT may play a key r o l e i n accelerating pulmonary l e c i t h i n synthesis i n t h e developing f e t u s . However, s i n c e t h e r a t e of l e c i t h i n production cont i n u e s t o increase a f t e r 21 DG when C K and CPT a c t i v i t i e s a r e declining, o t h e r regulatory mechanisms may be operative i n t h e t e r n f e t u s and neonate.METABOLIC STUDIES OF TRANSIENT TYROSINEMIA AND LATE METABOLIC ACIDOSIS I N PREMATURE INFANTS. S. Fernbach, R. Summons, A. Duffield and W. P e r e i r a , Depts. of Ped. and ...

No abstract

No abstract