Development of enzymes of glycerol metabolism in human fetal liver

The activities of three key enzymes of glycerol metabolism were measured in liver samples from 37 human fetuses ranging in gestational age from 18 weeks to term, from neonates (1-3 days) and from infants to 2 years. Glycerol kinase specific activity was constant throughout the period of fetal development examined, and was comparable to that measured in neonates and infants. However, the subcellular distribution of the activity changed markedly, being predominantly particulate in fetal samples and cytoplasmic in postnatal samples. The particulate activity had an elevated Km for glycerol. Cytoplasmic glycerol-3-phosphate dehydrogenase activity was very low in the fetal period, and then rose to adult levels during infancy. There were no kinetic differences between the fetal and postnatal activities. Mitochondrial glycerol-3-phosphate dehydrogenase activity rose somewhat after birth to near adult levels. The data indicate that glycerol can be metabolized by human fetal, neonatal and infant liver.     

Glycogen and enzymes of glycogen metabolism in rat embryos and fetal organs

Glycogen content and the enzymes of glycogen metabolism have been measured in the postimplantation rat embryo over a period ranging from 9.5 to 18.5 days of gestation. The earliest periods studied were at days 9.5 and 10.5 of gestation, when the yolk sac becomes vascularized and heart beat is first established. The next intervals were at days 10.5-11.5 when vascular connections via the allantoic placenta are formed. At 14.5 and 18.5 days of development, 4 entire organs were analyzed; heart, liver, kidney and brain. The metabolic apparatus of glycogen metabolism was concentrated in the embryo at 10.5 days, then the heart region, and in the heart itself at later stages.     

Activities of enzymes associated with the metabolism of glutathione in fetal rat liver and placenta

Glutathione S-transferase, glutathione peroxidase, glutathione reductase and gamma-glutamylcysteine synthetase activities were measured in fetal rat liver and placenta supernatant at the 16th and 20th days of pregnancy. Compared with adult liver, low activities were found in both fetal liver and placenta. Both selenium-dependent and selenium-independent glutathione peroxidase activities were present in fetal liver, but only the selenium-dependent activity augmented as parturition advanced. Selenium-independent glutathione peroxidase was found to be absent in placenta. The progress of gestation is accompanied by a significant increase in conjugating capacity toward 1-chloro-2,4-dinitrobenzene and 1,2-dichloro-4-nitrobenzene and a significant decrease toward 1,2-epoxy-3-(p-nitrophenoxy)propane in fetal liver. Glutathione S-transferase activity in rat placenta diminished from day 15 to day 20 of gestation. The elevation of enzymatic activities involved in the synthesis and recovery of glutathione, which takes place in fetal liver and placenta, was thought to be adaptively responsive to the changes that occurred in glutathione-consuming enzymes.     

Iron deficiency in the rat: effects on energy metabolism in brown adipose tissue

Mitochondria were prepared from the brown adipose tissue of control rats and animals made iron deficient by means of a low iron diet. The specific activities of the mitochondrial electron transport system (NADH, succinate and alpha-glycerophosphate oxidase activities) were markedly and significantly reduced in preparations of brown adipose tissue from the iron-deficient rats as compared with preparations from the control animals. In contrast, concentrations of the cytochrome pigments a + a3, and c + c1 were normal and cytochrome b was slightly reduced (18%) in the mitochondrial preparations from the iron-deficient animals. Treatment of the iron-deficient animals with triiodothyronine significantly increased the amount of brown fat present per kilogram of body weight in both control and iron-deficient rats, but did not significantly affect the specific activities of the mitochondrial electron transport system.     

Development of NADPH-consuming pathways in heart, brain and liver of the rat

The behavior of the principal NADPH-consuming pathways, fatty acid synthesis (-ATP-citrate lyase), transhydrogenase, glutamate dehydrogenase, glutathione reductase, NADPH-cytochrome c reductase and mitochondrial and cytoplasmic thioredoxin reductases were studied during the development of the heart, brain and liver of the rat. The liver is the tissue with highest NADPH-consuming activities. Transhydrogenase activity is highest in the heart; it undergoes two steep increases of activity, one at birth and another between 15 and 25 days. Liver cytoplasmic glutathione reductase activity increases mainly at birth. The activities in heart and brain are lower and the brain enzyme activity slightly increases throughout development. Liver NADPH-cytochrome c reductase activity greatly increases at weaning. The heart activity is the lowest, no changes taking place in the developmental period. Heart mitochondrial and brain cytoplasmic thioredoxin reductases undergo increases in activity at birth. The ratios of NADPH-producing/NADPH-consuming activities are constant in all tissues studied, and oscillate between congruent to 4 in fetuses to congruent to 2 in adults, the only exception being the adult heart ratio (congruent to 23). This otherwise constancy confirms that both processes are closely correlated.     

Mitochondrial energy metabolism in very premature neonates

The activity, amount and protein composition of pyruvate dehydrogenase (PDH) and respiratory chain complexes were studied in muscle mitochondria obtained postmortally from 6 neonates with a gestational age of 23-29 weeks. The activities of PDH and respiratory chain complex III and IV and citrate synthase were significantly lower in comparison with control children aged 0.5-2 and 2-20 years. Protein analyses revealed a parallel decrease in the content of PDH, respiratory chain complexes and their subunits in the cases analyzed. The observed immaturity of the mitochondrial energy-providing system suggests that significant development of mitochondrial energy metabolism occurs during the last 3 months of prenatal development. The metabolic disturbances of mitochondrial energy conversion associated with the low functional capacity and content of PDH and respiratory chain complexes may play an important role in the morbidity of very premature neonates.     

新生儿手术前后能量代谢特点研究

目的　通过对新生儿进行术前及术后连续7d的静息能量代谢值(restingenergyexpenditure,REE)测定,了解新生儿围术期能量代谢的特点,以提供合适的术后能量供给值。方法　1999年6月~2003年 6月期间接受手术新生儿患儿共 24例 (男 /女:15/9),于术前24h内接受间接能量测定,术后第1d起每日接受 1次复测,连续7d,比较他们手术前后静息能量消耗变化,并检验实测REE值与预计值的符合率。结果　术后与术前的静息能量消耗值无统计学差异;不同应激程度新生儿术后REE值组间比较差异无显著性意义。实测REE值与预计值相比,均低于公式预计值,差异有显著性意义(P<0.01)。预计值平均高出实测REE值18.5%。结论　新生儿术后能量消耗与术前相比无显著增高,但存在个体差异。不同应激状态对新生儿静息能量代谢值无影响。Schoefield公式预计值较新生儿实际测定REE值平均高出18.5%,按该公式指导术后新生儿喂养有引起过度喂养的危险。     

Cerebral energy metabolism in isovaleric acidaemia.

A newborn infant with an acute metabolic encephalopathy caused by isovaleric acidaemia had severe impairment of cerebral energy metabolism. This was detected by phosphorus and proton magnetic resonance spectroscopy. After treatment she made excellent clinical recovery, her spectroscopic abnormalities resolved, and she was neurologically normal at the age of 1 year.     

Resting energy expenditure in disorders of propionate metabolism

OBJECTIVES: During intercurrent illness children with methylmalonic acidemia were found to have increased resting energy expenditure (REE). We measured REE in children with disorders of propionate metabolism (methylmalonic and propionic acidemia) when they were well and compared the values with those predicted by the Schofield equation. STUDY DESIGN: Prospective study in tertiary care facility. REE was measured with open-circuit indirect calorimetry under standardized conditions. Predicted REE values were calculated with the Schofield equation. Fourteen subjects with propionic acidemia (n = 3) and methylmalonic acidemia (n = 11) were studied. RESULTS: The median REE was 690 kcal/d (range 186 to 1687 kcal/d), which is significantly reduced, representing 80% +/- 18% of that predicted by the Schofield height and weight equation (P <.01). REE was significantly lower in female compared with male patients for unknown reasons. There were no differences with age or neurologic state. REE was not further reduced in those with chronic renal failure. CONCLUSION: REE in patients with disorders of propionate metabolism is reduced when they are well.     

新生儿缺氧缺血性脑病时脑细胞能量代谢过程的监测

国内外研究已证实 ,围产期缺氧性脑损伤是多种病理机制交互作用的共同结果。在诸多损伤因素中 ,脑细胞能量衰竭被认为是首先发生的重要环节。由于能量产生障碍 ,致使细胞正常生理活动不能维持 ,各种损伤机制相继“瀑布”般发生 ,最终导致神经细胞不可逆性损伤。因此 ,揭示缺氧对能量合成的影响环节 ,并予以有针对性的治疗 ,对减轻脑损伤具有重要意义。1　缺氧对能量合成的影响环节营养物在生物体内氧化成水与二氧化碳并释放出能量的过程称之为生物氧化。以葡萄糖为代表的能源物质被摄入体内进入细胞 ,在线粒体中经三羧酸循环放出电子 ,经过…     

Activities of enzymes involved in glutamine metabolism in connection with energy production in the gastrointestinal tract epithelium of newborn, suckling and weaned piglets

Changes in the activity of enzymes involved in glutaminolysis and energy metabolism in the entire gastrointestinal (GI) tract of developing piglets are presented for the first time. The activities of glutaminase, glutamate dehydrogenase, oxoglutarate dehydrogenase, isocitrate dehydrogenase and alanine aminotransferase in the epithelium along the gastrointestinal tract from newborn, suckling (2-4 weeks old) and weaned (9 weeks old) piglets were investigated. The activity of glutaminase in the epithelium from the small intestine and colon was higher (p < 0.05) in weaned piglets than in newborn and suckling piglets. In addition, glutamate dehydrogenase and alanine aminotransferase activities in the small intestinal epithelium were higher (p < 0.05) for weaned piglets than for newborns. The activity of oxoglutarate dehydrogenase in the epithelium of the small intestine was significantly lower in newborn and suckling piglets compared with weaned individuals. The activity of isocitrate dehydrogenase in the epithelium along the gastrointestinal tract was higher (p < 0.05) for suckling and weaned piglets than for newborn piglets. The present data indicate that the utilization of substrates for energy production differs markedly between the stomach, small intestine and colon of growing piglets. Also, the capacity of enzymes in the epithelium of the GI tract to utilize acetyl-CoA as an energy substrate in the tricarboxylic acid cycle increased with piglet age. The epithelium of the GI tract of the newborn, suckling and weaned piglets showed a high capacity to metabolize alpha-ketoglutarate.     

Glutathione metabolism and antioxidant enzymes in children with Down syndrome

Oxidative stress has been proposed as a pathogenic mechanism of atherosclerosis, cell aging, and neurologic disorders in Down syndrome. This study demonstrates a systemic decrease of all glutathione forms, including glutathionyl-hemoglobin, in the blood of children with Down syndrome. Furthermore, we obtained a disequilibrium, in vivo, between the antioxidant enzyme activities.     

阿糖胞苷代谢关键酶基因在儿童恶性血液肿瘤中的表达

目的通过检测儿童急性白血病(AL)及非霍奇金淋巴瘤(NHL)骨髓细胞内阿糖胞苷(Ara-C)代谢关键酶———脱氧胞苷激酶(DCK)和胞苷脱氨酶(CDA)的基因表达及酶活性水平,探索DCK和CDA表达与临床疗效的关系。方法共计31例患儿,其中初诊27例(ALL20例,AML3例,NHL4例),复发4例(ALL2例,AML、NHL各1例),采集患儿骨髓细胞,采用荧光定量PCR检测细胞内DCK、CDA基因表达,核素液闪法检测细胞内DCK、CDA酶活性,统计分析各组患儿的检测结果。结果 (1)DCK:ALL和NHL患儿DCK mRNA与酶活性水平均明显高于AML患儿(P0.05);初治患儿均明显高于复发患儿(P0.05);(2)CDA:AML和复发患儿的CDA酶活性水平明显高于ALL、NHL和初治患儿(P0.05),但各组病例间的CDA mRNA表达差异无显著性(P0.05)。(3)DCK和CDAmRNA表达与酶活性水平呈高度正相关。结论 AML以及某些复发的血液肿瘤患儿,其总体DCK酶活性及基因表达水平降低,CDA酶活性水平增高。DCK和CDA酶活性可能与儿童恶性血液肿瘤疗效相关。     

Basal energy metabolism in goitrous and nongoitrous children

Measurement of basal energy metabolism was done in 61 nongoitrous (normal) and 134 goitrous children of both sexes between the age of 5 to 16 yr. It was observed that basal metabolic rate (BMR) decreases with age both in boys and girls. Boys had a higher metabolic rate compared to girls. BMR in nongoitrous children were lower than those from other part of the world but were almost comparable to the Indian standard. BMR values were significantly lowered in goitrous children (Stages II and III) as compared to nongoitrous children of both sexes in all age groups except in females of 13–16 yr (Stage II). There was an insignificant difference in BMR values between nongoitrous and goitrous children belonging to Stage Ia and Ib. So it was concluded that BMR is related to goitre size in goitrous children.