Energy metabolism in the granulation tissue of diabetic rats during cutaneous wound healing

The skin cells chiefly depend on carbohydrate metabolism for their energy requirement during cutaneous wound healing. Since the glucose metabolism is greatly hampered in diabetes and this might affect wound repair process. This prompted us to investigate the intermediate steps of energy metabolism by measuring enzyme activities in the wound tissues of normal and streptozotocin-induced diabetic rats following excision-type of cutaneous injury. The activities of key regulatory enzymes namely hexokinase (HK), phosphofructokinase (PFK), lactate dehydrogenase (LDH), citrate synthase (CS) and glucose-6 phosphate dehydrogenase (G6PD) have been monitored in the granulation tissues of normal and diabetic rats at different time points (2, 7, 14 and 21 days) of postwounding. Interestingly, a significant alteration in all these enzyme activities was observed in diabetic rats. The activity of PFK was increased but HK, LDH and CS showed a decreased activity in the wound tissue of diabetics as compared to normal rats. However G6PD exhibited an elevated activity only at early stage of healing in diabetic rats. Thus, the results suggest that significant alterations in the activities of energy metabolizing enzymes in the wound tissue of diabetic rats may affect the energy availability for cellular activity needed for repair process and this may perhaps be one of the factor responsible for impaired healing in these subjects. (Mol Cell Biochem 270: 71–77, 2005)     

The effects of diet on the maximal activities of glutaminase, citrate synthase, hexokinase, 6-phosphofructokinase and lactate dehydrogenase in the skin of haired and hairless mice of various ages.

1. The maximal activities of hexokinase (HK), 6-phosphofructokinase (PFK), lactate dehydrogenase (LDH), citrate synthase (CS) and glutaminase (GLU) which provide a quantitative indices of flux through several important pathways have been measured in the skin of haired Balb/c and hairless Balb/c (nu/nu) mice under normal and dietary stress. 2. The skin of old haired mice exhibited higher PFK and LDH activities with lower HK, CS and GLU activities. All activities of enzymes associated with energy metabolism in the skin of old hairless mice were higher than those in the skin of haired mice. 3. HK, LDH, CS and GLU activities were maintained at normal levels in the skin of haired mice when these mice were fed diets deficient in energy or protein components (HPLE, LPNE). These enzymes however were severely suppressed when mice were fed a diet deficient in both energy and protein components (LPLE). Recovery of activities of these enzymes to the control level was observed when mice were refed with the normal diet for a week.     

The effects of n-3 polyunsaturated fatty acids by gavage on some metabolic enzymes of rat liver

In this experimental study, the effect of fish n-3 fatty acids was studied on the some important enzymes of carbohydrate metabolism, hexokinase (HK), glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), lactate dehydrogenase (LDH), and malate dehydrogenase (MDH) in rat liver. Wistar albino rats of experimental group (n= 9) were supplemented fish omega-3 fatty acids (n-3 PUFA) as 0.4 g/kg bw. by gavage for 30 days in addition to their normal diet. Isotonic solution was given to the control group (n= 8) by the same way. At 30th day, the rats were killed by decapitation under ether anesthesia, autopsied and liver was removed. Spectrophotometric methods were used to determine the activities of above-mentioned enzymes in the liver. The n-3 PUFA caused increases in the activities of HK, G6PD, LDH, and MDH in comparison with control. These increases were statistically significant (P < 0.01) except 6PGD activity. As a result, n-3 PUFA may regulate the metabolic function of liver effectively by increasing HK, G6PD, 6PGD, LDH, and MDH enzyme activities of rat liver when added in enough amounts to the regular diet.     

Effect of copper on liver key enzymes of anaerobic glucose metabolism from freshwater tropical fish Prochilodus lineatus

We investigated the effect of copper on liver key enzymes of the anaerobic glucose metabolism (hexokinase, HK; phosphofructokinase, PFK; pyruvate kinase, PK; lactate dehydrogenase, LDH) as well as of the pentose pathway (glycose-6-phosphate dehydrogenase, G6PDH) from the fish Prochilodus lineatus. The fish were acclimated at either 20 degrees C or 30 degrees C at pH 7.0, transferred to water at pH 4.5 or 8.0, and exposed to 96 h-CL(50) copper concentrations. Copper accumulation in liver was higher in fish acclimated at 20 degrees C and maintained in water pH 8.0. Three-way analysis of variance revealed a significant effect of temperature on all enzymes, a significant effect of pH on all enzymes except for PK, and a significant effect of copper on only PFK, and LDH in pH 4.5 at 20 degrees C and, at 30 degrees C, on PFK and PK at pH 4.5 and 8.0, HK at pH 4.5 and G6PDH at pH 8.0. There were significant interactions between treatments for many enzymes. These changes suggest that the activity of enzymes in question is modified by a change in ambient water. At least at 30 degrees C, the overall reduction in the glycolytic enzyme activities of copper-exposed fish seems to reduce energy availability via glucose metabolism, thereby contributing to enhance copper toxic effects.     

Maximal activities of glutaminase, citrate synthase, hexokinase, 6-phosphofructokinase and lactate dehydrogenase in skin of immune-competent Balb/c and immune-deficient Balb/c (nu/nu) mice during wound healing.

1. The maximal activities of hexokinase (HK), 6-phosphofructokinase (PFK), lactate dehydrogenase, citrate synthase (CS) and glutaminase (GLU) which provide quantitative and qualitative indices of flux through several important metabolic pathways have been examined in the wounded skin of haired immune competent Balb/c mice and hairless immune deficient Balb/c (nu/nu) mice of various ages during the first ten days of wound healing. 2. The potential for glucose utilization and for aerobic metabolism as suggested by the maximal activities of HK, PFK, CS, were raised in the skin of Balb/c mice of various ages on all post wounding days. Increases in the maximal activity of GLU was observed only in the skin of 6 and 10 weeks old Balb/c mice during wound healing. 3. There was no evidence of a contribution to the maximal activity of GLU by infiltrating cells of the immune system to the wound site in the skin of either haired or hairless mice.     

Postnatal development of the energy supplying enzyme pattern in the rat brain

The activity of seven enzymes connected with energy-supplying metabolism was followed from the second day of life till adulthood (87th day). The enzymes selected were: 1. Triosephosphate dehydrogenase (TPDH), 2. Lactate dehydrogenase (LDH), 3. Glycerol-3-phosphate: NAD dehydrogenase (GPDH), 4. Hexokinase (HK), 5. Malate: NAD dehydrogenase (MDH), 6. Citrate syntase (CS) and 7. 3-Hydroxyacyl Co A dehydrogenase. Although some variations occurred, the enzyme profiles were characteristic of those of the nervous tissue from the second day of life onwards until adulthood and displayed relatively high activities of HK, CS and MDH and low activities of TPDH, LDH, GPDH and HOADH. The activities of all enzymes studied here increased during postnatal development and some reached adult values on the 14th day, that of TPDH on the 27th day and HOADH on the 41st day of life. The activities of MDH and GPDH did not attain the adult values still on the 41st day of life. The anaerobic energy supply capacity seems to increase transiently on the 31st day of life, i.e. at a developmental stage where the resistance against hypoxia is known to increase transiently.     

不同日龄和吊飞过程中桔小实蝇成虫飞行肌能量代谢相关酶活性的变化

【目的】明确桔小实蝇Bactrocera dorsalis(Hendel)飞行肌对能源物质的利用。【方法】通过生化方法测定了能源物质代谢相关5种酶[3-磷酸甘油醛脱氢酶(GAPDH)、3-磷酸甘油脱氢酶(GDH)、乳酸脱氢酶(LDH)、柠檬酸合酶(CS)和3-羟酰辅酶A脱氢酶(HOAD)]活性的变化。【结果】桔小实蝇成虫中所测的5种酶活性随日龄的变化而变化,4日龄GAPDH,GDH,LDH和CS活性最高,20日龄HOAD活性最高。吊飞过程中,GAPDH,GDH和CS的活性变化基本一致,随吊飞时间的延长活性逐渐升高;LDH和HOAD的活性变化雌、雄虫完全不同。雄虫LDH活性除吊飞2 h外其他时间均高于静息状态,雌虫则始终低于静息状态;雄虫HOAD活性只有吊飞24 h低于静息状态水平,而雌虫吊飞后HOAD活性一直在静息状态水平及以下波动。【结论】桔小实蝇飞行所利用的能源物质包括糖类和脂肪,以糖类能源为主。吊飞过程中,雄虫除可以进行高速有氧代谢以外,还具备一定的无氧代谢能力,而雌虫只进行有氧代谢;雄虫能利用脂肪供给能量,雌虫则几乎不动用脂肪。研究结果为进一步阐明桔小实蝇的迁飞行为机制提供了依据。     

Gene dosage effect in human triploid fibroblasts

Summary The activity of 13 cytoplasmic enzymes has been determined in fibroblast extracts from 9 triploid and 13 control lines. The results show a high activity for 2 X-linked enzymes, glucose 6-phosphate dehydrogenase and phosphoglycerate kinase. These data, together with cytogenetic observations, support the contention that 2 X chromosomes were active in the triploid lines.Abbreviations G6PD Glucose 6-phosphate dehydrogenase - 6PGD 6-phosphogluconate dehydrogenase - HK hexokinase - PGM phosphoglucomutase - PHI phosphohexoisomerase - PFK phosphofructokinase - ALD aldolase - TPI triosephosphate isomerase - PGK phosphoglycerate kinase - ENOL enolase - AK adenylate kinase - LDH lactic dehydrogenase - HBDH hydroxybutyrate dehydrogenase INSERM U. 129.INSERM U. 73.     

Glycolytic enzymes in the premolt field crab Paratelphusa hydrodromus (Milne-Edwards) (Crustacea)

The quantitative assay of hexokinase (HK), phosphorylase, phosphofructokinase (PFK), glucose 6-phosphate dehydrogenase (G-6-PDH), glycerol 3-phosphate dehydrogenase (G-3 PDH) and lactate dehydrogenase (LDH) revealed that coxal muscles compared to hepatopancreas contained higher activities of all the enzymes investigated. It appears that the coxal muscles of the premolt field crab has carbohydrate-based fuel economy. The hepatopancreas is a rich source of lipid and very poor source of glycogen. The activity of G-6-PDH is moderately high in the hepatopancreas. It seems that in this lipogenic tissue conversion of G-6-P to triose phosphate occurs predominately via pentose-phosphate pathway thus generating NADPH for lipogenesis. The relative G-3PDH ad LDH activities in hepatopancreas and coxal muscles led us to believe that the reconversion of NAD from NADH in hepatopancreas nd muscle flexor is effected by glycerol 3-phosphate shuttle, whereas in muscle extensor it is achieved by both G-3PDH and LDH activities.     

Seasonal changes in the activities of glycolytic enzymes from liver and skeletal muscle of Rana perezi

Glycogen phosphorylase (GP), Hexokinase (HK), Phosphofructokinase (PFK), Pyruvate kinase (PK) and Lactate dehydrogenase (LDH) activities from skeletal muscle and liver were measured in Rana perezi for the four seasons of the year. Skeletal muscle showed a decrease in PFK, PK and LDH activity during winter and summer. Liver displayed an increase in GP activity in spring and in PK and LDH in autumn.     

社群等级对金乌贼行为表型及能量代谢的影响

采用实验生态学方法,在室内水槽条件下研究了金乌贼(Sepia esculenta Hoyle,1885)繁殖过程中社群等级的形成对其行为表型和能量代谢的影响,分析测定了不同优势等级雌雄个体腕部肌肉和性腺组织中己糖激酶(Hexokinase, HK)、丙酮酸激酶(Pyruvate kinase, PK)、乳酸脱氢酶(Lactate dehydrogenase, LDH)、苹果酸脱氢酶(Malate dehydrogenase, MDH)、柠檬酸合酶(Citrate synthetase, CS)活性以及乳酸(Lactic acid, LD)含量。结果显示:(1)金乌贼繁殖期不同优势等级雌雄个体之间行为表型具有显著差异,优势雄性个体游动悬浮、争斗时间显著高于劣势个体,而优势雌性个体静止伏底时间高于劣势个体,游动悬浮时间低于劣势雌性;(2)优势雄性个体在争斗过程中主要通过无氧代谢提供能量,而处于游动悬浮状态时通过有氧代谢提供能量。主要表现在优势雄性个体肌肉中无氧代谢酶(PK、HK、LDH)活性显著高于劣势个体(P0.05),有氧代谢酶(MDH、CS)活性也显著高于劣势个体,雌性个体之间则差异不显著(P0.05);(3)繁殖期雌性个体通过减少运动量来储存能量用于产卵繁殖,主要表现在优势雌性个体肌肉中有氧代谢酶(MDH、CS)活性低于劣势个体,而在性腺中恰恰相反;(4)运动表型与能量代谢之间存在显著相关性,表现在游动悬浮时间与有氧代谢酶(MDH、CS)活性呈显著正相关(P0.001),争斗时间与无氧代谢酶(PK、HK、LDH)及乳酸(LD)含量呈显著正相关(P0.05)。结果表明,社群等级高的雄性个体运动能力强,具有较高的生存适应性。而社群等级高的雌性个体多处于静止状态,以便更好地储存能量用于繁殖。研究结果为金乌贼健康苗种培育以及规模化繁殖技术优化提供了理论依据。     

Effects of prolactin and androgens on enzymes of carbohydrate metabolism in prostate of castrated bonnet monkeys Macaca radiata (Geoffroy).

Effects of prolactin (PRL), bromocriptine (Br), testosterone propionate (TP), dihydrotestosterone (DHT) and the combinations of these androgens with PRL/Br on the specific activities of caudal and cranial prostatic cellular enzymes involved in carbohydrate metabolism in castrated mature bonnet monkeys have been studied. Castration decreased all the enzymes studied such as hexokinase (HK), 6-phosphofructokinase (6-PFK), glyceraldehyde-3-phosphate dehydrogenase (G-3-PD), pyruvate kinase (PK), glucose-6-phosphate dehydrogenase (G-6-PD) and 6-phosphogluconate dehydrogenase (6-PGD) in the cranial and caudal prostates. PRL elevated the activities of all the enzymes above normal except G-3-PD of cranial lobe. In the caudal lobe, PRL brought back the activities of HK, PFK, PK, G-6-PD to normal and 6-PGD above normal except G-3-PD. TP/DHT treatment increased all the enzymes in both the lobes. PRL given along with TP/DHT further enhanced the androgen action with regard to HK, PK, G-6-PD and 6-PGD of cranial and PFK, G-3-PD, PK, G-6-PD and 6-PGD of caudal lobe. Br treatment did not produce any alteration of these enzymes in both the lobes. In the cranial lobe, during Br+TP/DHT treatment, the stimulating effects of androgen were unaffected on all the enzymes except PK. On the other hand in the caudal, the stimulatory effects of androgens were affected and the activities of HK, PFK, PK and 6-PGD were significantly decreased. The present results suggest that PRL has a direct as well as a synergistic action with androgens on enzymes of EMP and HMP shunt in the prostates of monkeys.     

The role of glucose metabolism and insulin resistance in cardiac remodelling induced by cigarette smoke exposure

The aim of this study is to evaluate whether the alterations in glucose metabolism and insulin resistance are mechanisms presented in cardiac remodelling induced by the toxicity of cigarette smoke. Male Wistar rats were assigned to the control group (C; n = 12) and the cigarette smoke-exposed group (exposed to cigarette smoke over 2 months) (CS; n = 12). Transthoracic echocardiography, blood pressure assessment, serum biochemical analyses for catecholamines and cotinine, energy metabolism enzymes activities assay; HOMA index (homeostatic model assessment); immunohistochemistry; and Western blot for proteins involved in energy metabolism were performed. The CS group presented concentric hypertrophy, systolic and diastolic dysfunction, and higher oxidative stress. It was observed changes in energy metabolism, characterized by a higher HOMA index, lower concentration of GLUT4 (glucose transporter 4) and lower 3-hydroxyl-CoA dehydrogenase activity, suggesting the presence of insulin resistance. Yet, the cardiac glycogen was depleted, phosphofructokinase (PFK) and lactate dehydrogenase (LDH) increased, with normal pyruvate dehydrogenase (PDH) activity. The activity of citrate synthase, mitochondrial complexes and ATP synthase (adenosine triphosphate synthase) decreased and the expression of Sirtuin 1 (SIRT1) increased. In conclusion, exposure to cigarette smoke induces cardiac remodelling and dysfunction. The mitochondrial dysfunction and heart damage induced by cigarette smoke exposure are associated with insulin resistance and glucose metabolism changes.     

Ontogenetic development of energy-supplying enzymes in rat and guinea-pig heart

The purpose of the present study was to compare the ontogenetic development of the activity of myocardial energy-supplying enzymes in two mammalian species, differing significantly in their level of maturation at birth. The animals were investigated during the late prenatal period and 2, 7, 14, 21, 25, 30, 63, 120 and 730 days after birth in the rat and 2, 21, 84 and 175 days in the guinea-pig. The following enzymes were assayed in the right and left ventricular myocardium: lactate dehydrogenase (LDH, lactate uptake and/or formation), triose phosphate dehydrogenase (TPDH, carbohydrate metabolism), glycerol phosphate dehydrogenase (GPDH, glycerol-P shuttle)), hexokinase (HK, glucose phosphorylation), malate dehydrogenase (MDH, tricarboxylic cycle), citrate synthase (CS, tricarboxylic cycle) and hydroxyacyl-CoA dehydrogenase (HOADH, fatty acid breakdown). The rat heart, highly immature at birth, exhibits three different developmental patterns of energy-supplying enzymes, identical in both ventricles: (i) two mitochondrial enzymes of aerobic metabolism (CS, HOADH) and GPDH have a relatively low activity at the end of prenatal life; thereafter their activity steadily increases, approaching the adult levels between the 3rd and 4th postnatal weeks. A significant decrease was observed between the 4th and 24th months. (ii) MDH and LDH: prenatal values were significantly higher as compared with the 2nd postnatal day; after this period the activities increased up to adulthood (4 months) and decreased during senescence. (iii) The activities of HK and TPDH are characterized by only moderate changes during development. HK differs from all other enzymes by the highest prenatal values, which exceed even adult values. In contradiction to the rat heart, the developmental differences in more mature guinea-pig heart were significantly less pronounced. The only ontogenetic differences observed were the lower activities of enzymes connected with aerobic metabolism at the end of the prenatal period. Our results point to possible differences in the development of adaptive metabolic pathways in animals with different levels of maturation at birth.     

HUNTINGTON''S CHOREA: POST MORTEM ACTIVITY OF ENZYMES INVOLVED IN CEREBRAL GLUCOSE METABOLISM

Abstract— The loss of at least two different cell types in the basal ganglia of the choreic brain led us to examine the activity of enzymes involved in the metabolism of glucose. Cellular ATPase, HK, G6-PDH, PFK., LDH, GDH were measured. Post mortem stability studies indicated that these enzymes were more unstable in human brain than mouse brain. The most stable enzyme was GDH. HK activity appeared to increase after freezing, suggesting release from another compartment. PFK and G6-PDH activity decreased by 70% over the usual time and temperature period for autopsy. In the autopsied brain tissue we were still able to measure significant activities that allowed us to determine the distribution of these enzymes and the similar post mortem handling of control and choreic brain allowed us to compare these two groups.
The activity of HK and G6-PDH was higher in the frontal cortex than in the basal ganglia. Ouabain insensitive ATPase and PFK were higher in the basal ganglia than the frontal cortex.
GDH activity, an enzyme that is very active in glial cells, was increased in the choreic globus pallidus, an area with a very high glial to neuronal cell ratio.
Although there was a wide variation in PFK activity that appeared to be related to the pre-mortem clinical state there was a significant decrease in PFK activity in the putamen of choreic post mortem brain when compared to controls.
These findings do not indicate an absolute defect in any of the enzymes studied in choreic brain but further studies might prove worthwhile.     

Antihyperglycemic effect of aqueous and ethanolic extracts of Gongronema latifolium leaves on glucose and glycogen metabolism in livers of normal and streptozotocin-induced diabetic rats

The present study was designed to investigate the antihyperglycemic effects of aqueous and ethanolic extracts from Gongronema latifolium leaves on glucose and glycogen metabolism in livers of non-diabetic and streptozotocin-induced diabetic rats. To investigate the effects of aqueous or ethanolic leaf extracts of G. latifolium, non-diabetic and STZ diabetic rats were treated twice daily (100 mg/Kg) for two weeks. Diabetic rats showed a significant decrease in the activities of hepatic hexokinase (HK), phosphofructokinase (PFK) and glucose-6-phosphate dehydrogenase (G6PDH) and an increase in glucokinase (GK) activity. The levels of hepatic glycogen and glucose were also increased in diabetic rats. However, there were no significant differences in the activities of glucose-6-phosphatase (G6Pase) in treated and untreated diabetic rats. The ethanolic extract significantly increased the activities of HK (p<0.01), PFK (p<0.001) and G6PDH (p<0.01) in diabetic rats, decreased the activity of GK (p<0.05) and the levels of hepatic glycogen (p<0.01) and both hepatic (p<0.001) and blood glucose (40%). The aqueous extract of G. latifolium was only able to significantly increase the activities of HK and decrease the activities of GK but did not produce any significant change in the hepatic glycogen and both hepatic and blood glucose content of diabetic rats. Our data show that the ethanolic extract from G. latifolium leaves has antihyperglycemic potency, which is thought to be mediated through the activation of HK, PFK, G6PDH and inhibition of GK in the liver. The ethanolic extract is under further investigation to determine the chemical structure of the active compound(s) and its/their mechanism of action.     

Effect of vitamin D3 on metabolic processes in rat erythrocytes under extreme factors

The effects of vitamin D3 (as an ingredient of the preparation "Videchol") on the activity of some glycolysis enzymes (lactic dehydrogenase, LDH; pyruvate kinase PK; hexokinase HK) and of pentose phosphate shunt (glucose-6-phosphate dehydrogenase), and also on the changes of metabolites concentration levels: ATP, NAD+, pyruvate and lactate following the administration of the vitamin to the control group rats and animals irradiated by low rate ionizing radiation were established. "Videchol" administration leads to the of LDH activity decrease within 10 days, of HK activity within 20 days and to the decrease of PK activity within 5 and 20 days after the experiment beginning. In the low dose radiation conditions a reconnection of carbohydrates' metabolism from glycolisys into pentose phosphate pathway in the erythrocytes was observed. The administration of vitamin D3 as a component of the preparation "Videchol" following the low rate radiation background facilitates the normalization of LDG, PK and HK activities in comparison with the same parameters of only irradiated rats. The studies on LDH--reaction kinetics showed the redistribution of the LDH isozymes pattern with different K(m) means for pyruvate in the rats subjected to the joint action of low dose chronical radiation and "Videchol" occurred.     

Prenatal developmental changes in glucose transporters, intermediary metabolism and hormonal receptors related to the IGF/insulin-glucose axis in the heart and adipose tissue of bovines

Glucose transporter ontogenesis is likely to play a key role in glucose uptake by foetal tissues in order to satisfy their energy requirements. We thus investigated developmental changes in the bovine heart and perirenal adipose tissue in two glucose transporter isoforms, namely GLUT1 and GLUT4, the latter being responsible for the regulation of glucose uptake by insulin. Other key players of the glucose/insulin axis were also assessed. Plasma glucose concentration in the foetus was lower at 8 and 8.5 months of age than previously. In the heart, GLUT1 protein level markedly decreased between 3 and 4 months of age, whereas the number of insulin and IGF-I binding sites continually decreased, especially between 7 and 8 or 8.5 months of age. On the contrary, the GLUT4 level increased until 8 months of age and remained high until 2 weeks after birth. The activities of enzymes of glucose metabolism (namely phosphofructokinase [PFK] and lactate dehydrogenase [LDH]) increased throughout gestation and reached a plateau at 6 and 8.5 months of age for PFK and LDH, respectively. The activities of enzymes involved in fatty acid metabolism increased especially at birth. In perirenal adipose tissue, high mitochondrial activity was detected before birth which is a characteristic of brown adipose tissue. Furthermore, lipoprotein lipase activity and GLUT4 protein level markedly increased to reach a maximum at 6-7 and 8 months of age, and sharply decreased thereafter, whereas GLUT1 protein level increased between 6 and 7 months of age. In conclusion, considerable changes in the regulation of the insulin/glucose axis were observed from 6 months onwards of foetal development in both the heart and adipose tissue of cattle, which probably alters the potential of these tissues to use glucose or fat as energy sources.     

Effect of orchidectomy and testosterone substitution on enzyme activities and DNA content in rat liver and epididymal fat

Orchidectomy of rats resulted in increased concentration and whole organ amount of DNA both in the epididymal fat pad and liver. Liver hexokinase (HK) and phosphofructokinase (PFK) activities were raised after orchidectomy, but were normalized by testosterone substitution. Several glycolytic enzymes, and fumarase and aspartate aminotransferase were increased by orchidectomy in epididymal fat. Most of the enzyme changes tended to normalize after testosterone administration. Activities of NADPH generating enzymes were increased after orchidectomy both in liver and epididymal fat. When related to DNA, several enzyme activities in both tissues fell following castration. However, liver HK, PFK and NADPH generating enzymes, as well as epididymal fat HK and isocitrate dehydrogenase were elevated after castration also when related to DNA. The results suggest that the influence of testosterone on cell proliferation is organ-specific. The observed enzyme alterations after orchidectomy might partly explain fat accumulation and hyperlipoproteinemia encountered in castrates.     

Chronic hypoxia in development selectively alters the activities of key enzymes of glucose oxidative metabolism in brain regions

The immature brain is more resistant to hypoxia/ischemia than the mature brain. Although chronic hypoxia can induce adaptive-changes on the developing brain, the mechanisms underlying such adaptive changes are poorly understood. To further elucidate some of the adaptive changes during postnatal hypoxia, we determined the activities of four enzymes of glucose oxidative metabolism in eight brain regions of hypoxic and normoxic rats. Litters of Sprague-Dawley rats were put into the hypoxic chamber (oxygen level maintained at 9.5%) with their dams starting on day 3 postnatal (P3). Age-matched normoxic rats were use as control animals. In P10 hypoxic rats, lactate dehydrogenase (LDH) activity in cerebral cortex, striatum, olfactory bulb, hippocampus, hypothalamus, pons and medulla, and cerebellum was significantly increased (by 100%–370%) compared to those in P10 normoxic rats. In P10 hypoxic rats, hexokinase (HK) activity in hypothalamus, hippocampus, olfactory bulb, midbrain, and cerebral cortex was significantly decreased (by 15%–30%). Neither -ketoglutarate dehydrogenase complex (KGDHC, which is believed to have an important role in the regulation of the tricarboxylic acid [TCA] cycle flux) nor citrate synthase (CS) activity was significantly decreased in the eight regions of P10 hypoxic rats compared to those in P10 normoxic rats. In P30 hypoxic rats, LDH activity was only increased in striatum (by 19%), whereas HK activity was only significantly decreased (by 30%) in this region. However, KGDHC activity was significantly decreased in olfactory bulb, hippocampus, hypothalamus, cerebral cortex, and cerebellum (by 20%–40%) in P30 hypoxic rats compared to those in P30 normoxic rats. Similarly, CS activity was decreased, but only in olfactory bulb, hypothalamus, and midbrain (by 9%–21%) in P30 hypoxic rats. Our results suggest that at least some of the mechanisms underlying the hypoxia-induced changes in activities of glycolytic enzymes implicate the upregulation of HIF-1. Moreover, our observation that chronic postnatal hypoxia induces differential effects on brain glycolytic and TCA cycle enzymes may have pathophysiological implications (e.g., decreased in energy metabolism) in childhood diseases (e.g., sudden infant death syndrome) in which hypoxia plays a role.