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Biomedical subjects

S Zierz

Publications and source records attributed to S Zierz.

161 records · Page 9Linked to original sources
PubMed1988

[Concordance of Kearns-Sayre syndrome and Klinefelter syndrome].

In the last years the Kearns-Sayre-Syndrome has been defined with the typical trias of chronic external ophthalmoplegia, pigmentary retinal dystrophy and cardiac conduction defects. Today it is no longer believed to present an entity but a variant of the multiple plussymptoms of the ophthalmoplegia-plus group. In pediatrics the existence of this clinical disorder is not yet well acknowledged. The case of a 16-year-old patient is used as an example for the impressive clinical symptoms and the involvement of several organs in this clinical disorder. The combination with a Klinefelter-Syndrome has not previously been reported.

Adolescent↗
PubMed1987

Different sites of inhibition of carnitine palmitoyltransferase by malonyl-CoA, and by acetyl-CoA and CoA, in human skeletal muscle.

The inhibition of carnitine palmitoyltransferase (CPT, EC 2.3.1.21) by malonyl-CoA, acetyl-CoA and free CoA was studied in sonicated skeletal-muscle homogenates from normal human subjects and from five patients with a mutant CPT [Zierz & Engel (1985) Eur. J. Biochem. 149, 207-214]. (1) Malonyl-CoA, acetyl-CoA and CoA were competitive inhibitors of CPT with palmitoyl-CoA. (2) Acetyl-CoA and CoA inhibited normal and mutant CPT to the same degree, whereas malonyl-CoA inhibited mutant CPT more than normal CPT. (3) Triton X-100 abolished the inhibition of normal CPT by malonyl-CoA, but not by acetyl-CoA or CoA. Triton X-100 by itself caused loss of activity of the mutant CPT. (4) In the concentration range 0.1-0.4 mM, the inhibitory effects of any two of the three inhibitors were synergistic. (5) The inhibitory constants (Ki) for acetyl-CoA and CoA were close to 45 microM. The Ki for malonyl-CoA was 200-fold lower, or 0.22 microM. Addition of 40 microM-acetyl-CoA or CoA resulted in a 3-fold increase in the Ki for acetyl-CoA. Addition of 20 microM-CoA resulted in a 3-fold increase in the Ki for acetyl-CoA. (6) The findings indicate that acetyl-CoA and CoA can inhibit CPT at the catalytic site or a nearby site which is different from that at which malonyl-CoA inhibits CPT. (7) The fact that small changes in the concentration of acetyl-CoA and CoA can antagonize the inhibitory effect of malonyl-CoA suggests that these compounds could modulate the inhibition of CPT by malonyl-CoA.

Acetyl Coenzyme A↗
PubMed1987

Are there two forms of carnitine palmitoyltransferase in muscle?

Mitochondria were isolated from rat skeletal muscle, heart, and liver and from human skeletal muscle. The distribution of CPT I and CPT II was studied by measuring CPT activity and malonyl-CoA sensitivity before and after disruption of the mitochondria. Neither sonication, freezing and thawing, nor detergent treatment increased CPT activity in heart or skeletal muscle mitochondria, but these procedures did increase CPT activity in liver mitochondria. These results cannot be attributed to different kinetics of CPT I and II to palmitoyl-CoA or carnitine, or to different effects of electrolytes on CPT I and II. Sensitivity to inhibition by malonyl-CoA also failed to distinguish convincingly between CPT I and II in skeletal muscle. Because the presence of CPT I and II in muscle cannot be ascertained, the notion of a selective CPT I or II deficiency in muscle cannot be entertained.

Acyltransferases↗
PubMed1985

Regulatory properties of a mutant carnitine palmitoyltransferase in human skeletal muscle.

Carnitine palmitoyltransferase (EC 2.3.1.21) was studied in sonicated muscle homogenates of seven patients who had recurrent attacks of myoglobinuria and marked deficiency of carnitine palmitoyltransferase in the isotope exchange assay, and in control subjects. When L-palmitoylcarnitine was reduced from 0.5 mM to 0.05 mM in the isotope exchange assay, enzyme activity returned to normal in the patients but was not significantly altered in the controls. When the forward assay was performed in the presence of 80 microM palmitoyl-CoA and 0.1% albumin, all patients showed normal carnitine palmitoyltransferase activity. The apparent Km values for DL-carnitine and palmitoyl-CoA were also normal in the patients. When albumin was omitted from the forward assay, 72-105% of the initial activity was observed in the controls, but only 31-55% in the patients. When the palmitoyl-CoA concentration in the forward assay exceeded 0.08 mM the enzyme activity was inhibited in both patients and controls, but the inhibition was significantly greater in the patients. The addition of either L-palmitoylcarnitine or DL-palmitoylcarnitine to the forward assay progressively inhibited enzyme activity in both patients and controls, but the inhibition was significantly greater in the patients. In the controls but not the patients D-palmitoylcarnitine was less inhibitory than the L-isomer or the DL-racemate. When the forward assay was performed with muscle homogenates preincubated with 0.4% Triton X-100 only 7-21% of the original enzyme activity remained in the patients, but 86-110% was found in the controls. Increasing concentrations of malonyl-CoA inhibited both the forward and the isotope exchange assays. When the inhibition was maximal, only 14-18% of the CPT activity remained in homogenates of patients but 32-47% in homogenates of controls. The I50 (median inhibitory concentration) and Ki values for malonyl-CoA determined in the forward assay were not significantly different in the patients and controls. The data imply that CPT deficiency is caused by altered regulatory properties of a mutant enzyme and/or by altered interaction between the enzyme and its membranous environment rather than lack of catalytically active CPT I, II or both. The mutant CPT would be most vulnerable to inhibition by its substrate and/or product when lipid metabolism is stressed. This could also explain why the symptoms differ from muscle carnitine deficiency, and why so little lipid accumulates in muscle in CPT deficiency.

Acyltransferases↗
PubMed1985

Metabolic zonation in liver of diabetic rats. Zonal distribution of phosphoenolpyruvate carboxykinase, pyruvate kinase, glucose-6-phosphatase and succinate dehydrogenase.

The activities and zonal distribution of key enzymes of carbohydrate metabolism were studied in livers of diabetic rats. 48 h after alloxan treatment the following alterations were observed, intermediate values being reached after 24 h: Blood glucose, acetoacetate and beta-hydroxybutyrate were increased to more than 500%; liver glycogen was reduced to about 10%. Portal vein insulin was reduced to below 10%, portal glucagon was increased to almost 200%. The glucogenic enzymes phosphoenolpyruvate carboxykinase and glucose-6-phosphatase were enhanced to 320% and 150%, respectively. The glycolytic enzymes glucokinase and pyruvate kinase L (differentiated from the M2 isoenzyme with a specific anti-L-antibody) were lowered to 50% and 75%, respectively. The citrate cycle enzyme succinate dehydrogenase remained unchanged. The normal periportal to perivenous gradient of phosphoenolpyruvate carboxykinase of about 3:1, as measured in microdissected tissue samples, was enhanced to about 4:1 with activities elevated to 230% and 190%, respectively, in the two zones. The normal periportal to perivenous gradient of pyruvate kinase L of about 1:1.7, as determined with the microdissection technique, was reduced to about 1:1.4 with levels lowered to 55% and 45%, respectively, in the two zones. The even zonal distribution of pyruvate kinase M2 remained unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Glucostat capacity and metabolic zonation in rat liver after portocaval anastomosis.

The activities and zonal distribution of key enzymes of carbohydrate metabolism were studied in livers of rats after end-to-side portocaval anastomosis. Sham-operated control animals with the same periods of interruption of hepatic blood supply as the shunted animals were pair-fed. The following alterations were observed: Food uptake was reduced to about 20% at the first postoperational day; it was then increased continuously to about 70% at day 8. Body weight, after a small 10% postoperational decrease, remained unaltered, but liver weight was lowered to 55% at day 8 and then stayed constant. The total glycogen reserves of the liver (g X 100 g body weight-1) were reduced, after a transient fall to about 10% at day 1-4, to about 25%. The total activity of the glucogenic phosphoenolpyruvate carboxykinase (mumol . min-1 X 100 g body weight-1) was diminished, after a transient increase to 190% and 150% at day 1 and 2 respectively, to about 55% from day 8 onwards. The total activity of the glucogenic glucose-6-phosphatase was lowered without a transient rise to about 30%. The total activities of the glycolytic pyruvate kinase isoenzyme L and glucokinase were decreased continuously to about 40% at day 8; that of the citrate cycle enzyme succinate dehydrogenase was lowered parallel with liver weight to 55%. The transient decrease of the glycogen reserves and the intermediate increase of the phosphoenolpyruvate carboxykinase capacity were due to the operational stress, since they were observed also in the sham-operated control animals. All other alterations, the decrease of liver weight and of the capacities of both gluconeogenic and glycolytic key enzymes, were specific for the portocaval anastomosis. The normal periportal to perivenous gradient of phosphoenolpyruvate carboxykinase of about 3.5:1, as measured in microdissected tissue samples, remained the same with specific activities reduced to about 80% each in the two zones. The normal periportal to perivenous gradient of pyruvate kinase L of about 1:1.7 was equalized with levels lowered to 35% and 23%, respectively, in the two zones. The normal periportal to perivenous gradients of glucose-6-phosphatase and succinate dehydrogenase, demonstrated histochemically, were essentially maintained with perivenous bridging occurring transiently at day 4 and 8.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Alteration with dietary state of the activity and zonal distribution of adenylate cyclase stimulated by glucagon, fluoride and forskolin in microdissected rat liver tissue.

Adenylate cyclase activated by glucagon, fluoride and forskolin was measured in liver homogenates and microdissected periportal and perivenous tissue of fed and fasted rats. A radiochemical microtest, more sensitive by 2-3 orders of magnitude as compared with the usual assay, was established for the determination of the activity in liver samples corresponding to 200-600 ng dry weight. In liver homogenates from fasted as compared to fed animals the glucagon-stimulated and fluoride-stimulated activity was increased by 1.65-fold, while the basal and the forskolin-stimulated activity remained the same. In microdissected tissue of both fed and fasted animals the activity was stimulated in about 60% of the samples by glucagon, fluoride and forskolin (responsive samples). However, in about 40% of the microdissected tissue samples the activity could not be stimulated by any of the above activators (non-responsive samples). In responsive microdissected tissue of fasted as compared to fed animals, the glucagon-stimulated and fluoride stimulated activity but not the basal and the forskolin-activated activity was increased by 2-3-fold. In responsive microdissected samples of fed animals neither the basal nor the stimulated activities showed a significant periportal to perivenous gradient. In samples of fasted animals, however, a zonal gradient was observed for the glucagon-stimulated activity exhibiting a 1.5-fold higher rate in the perivenous zone.

Adenylyl Cyclases↗
PubMed1984

Alteration in zonation of succinate dehydrogenase, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase in regenerating rat liver.

Parenchymal activities (mumol . min-1 . g liver-1) and distributions of mitochondrial succinate dehydrogenase, cytosolic phosphoenolpyruvate carboxykinase and microsomal glucose-6-phosphatase were studied in regenerating rat liver after two thirds partial hepatectomy. Succinate dehydrogenase activity remained constant with a slight and transient increase for a few hours after operation. The typical periportal localization was changed to an almost even distribution from 8 h to 7 days; it was fully restored after 14 days. Phosphoenolpyruvate carboxykinase activity was increased by 1.8 fold 24 h after surgery; it remained enhanced until about 72 h. The normal periportal to perivenous enzyme gradient was diminished or replaced by a homogeneous distribution between 8 h and 7 days; the zonal heterogeneity was regained after 14 days. Glucose-6-phosphatase activity remained constant after partial hepatectomy. The normal periportal maximum was lost between 4 h and 36 h; the activity became more equally distributed and was even shifted towards the perivenous zone. After 48 h the zonal distribution was reestablished. The results indicate that after partial hepatectomy the gluconeogenic capacity of the liver remnant is increased and that this increase is accompanied by a loss of the normal heterogeneity which is typical for the glucostat function of the organ. They reveal in addition that the three enzymes, representing three different subcellular compartments, change their zonal heterogeneity individually rather than synchronously.

Animals↗
PubMed1983

Fructose, fructose 1-phosphate, and glyceraldehyde breakdown in carbohydrate metabolism.

Recent investigations showed that all enzymes that are involved in the catabolism of fructose via fructose 1-phosphate (F-1-p) are present in the bovine lens. The present studies were performed to provide information regarding the extent to which fructose, F-1-p and glyceraldehyde (GA) are actually catabolized via this pathway, and how they increase the lactate, alpha-glycerophosphate and glycerol concentrations. Incubation was performed with a homogenate of bovine lens equator. F-1-p, and particularly fructose + ATP, considerably increased lactate and alpha-glycerophosphate concentrations, while the glycerol concentration remained unchanged compared to controls. Lactate formation through GA was not observed; while small amounts of glycerol and alpha-glycerophosphate are formed, it seems that the major part is transformed to glycerate. The results show that the further breakdown of lenticular fructose occurs via F-1-p and that the phosphorylated C3 fragments (dihydroxyacetone phosphate) are transferred to the energy metabolism, which is not the case with GA.

Animals↗
PubMed1983

Distribution of pyruvate kinase type L and M2 in microdissected periportal and perivenous rat liver tissue with different dietary states.

Pyruvate kinase type L and M2 activities were measured in microdissected periportal and perivenous liver tissue from rats in different dietary states. A specific antibody against pyruvate kinase type L was used to distinguish the two isoenzymes. Using separated cells it was found that the L-isoenzyme was essentially restricted to the parenchymal and the M2-isoenzyme to the non-parenchymal cells. Pyruvate kinase type L activity in the perivenous zone was about twice as high as in the periportal zone in both male and female fed rats. Starvation for 48 h led to a decrease of the overall activity and to a lower perivenous-periportal gradient. After refeeding for 48 h the overall activity and the gradient were increased to above the normal level. Pyruvate kinase type M2 was homogenously distributed within the liver acinus. After 48 h starvation no change in the overall activity nor in the zonal distribution was observed. Refed rats exhibited a slightly reduced overall activity. Since the hepatocytes contain the total regulatory L- but no M2-pyruvate kinase the heterogeneous distribution of the L-isoenzyme under different dietary states supports the model of metabolic zonation of liver parenchyma with glycolysis predominantly in the perivenous zone.

Animals↗
PubMed1983

Perinatal development of the distributions of phosphoenolpyruvate carboxykinase and succinate dehydrogenase in rat liver parenchyma.

Parenchymal distributions and activities of mitochondrial succinate dehydrogenase and cytosolic phosphoenolpyruvate carboxy-kinase were studied during perinatal development of rat liver. 1. Succinate dehydrogenase activity increased almost linearly from day 5 before to day 5 after birth. Hepatocytes with higher enzyme activities were disseminated heterogeneously, zonal heterogeneity developed during the second week. 2. Cytosolic phosphoenolpyruvate carboxykinase was not detectable before birth; it was induced to high levels during day 1 and increased further to a maximum during days 5 to 10. It decreased again to adult levels at the end of the third week. The enzyme distribution already showed signs of a zonal heterogeneity at day 1, which became fully developed during the second week. The results indicate that the zonal heterogeneity typical of adult liver was established for the two enzymes during the second week of life. They revealed in addition that the two enzymes, representing two different subcellular compartments, had an individual development towards the zonal heterogeneity.

Age Factors↗
PubMed1982

Investigations of the enzymes involved in the fructose breakdown in the cattle lens.

By introducing fructose into the glycolysis, it is possible to stimulate ATP formation. As is the case in animal experiments, in human lenses, too, the first step in the phosphorylation to fructose-1-phosphate via the enzyme ketohexokinase. The present investigation deals with the question whether enzymes present in the lens are responsible for the further steps in fructose degradation. Particularly the aldolase isoenzyme C splits fructose-1-phosphate into glyceraldehyde and dihydroxyacetone phosphate in the same way as in glucose catabolism. Dihydroxyacetone phosphate can further be directly degraded and thus utilized to ATP formation. From glyceraldehyde, glycerol (aldose reductase) or glycerate (aldehyde dehydrogenase) can be formed. The presence of triosekinase, which phosphorylates glyceraldehyde directly to glyceraldehyde-3-phosphate, could only be determined in the lens tissue of young animals. The presence of glycerokinase (glycerol leads to glycerophosphate) could not be verified. Thus, in the lens tissue 1 ATP molecule net per fructose molecule can be formed. In older age, the glucose breakdown is limited by hexokinase and phosphofructokinase, so that the glucose, after transformation via the sorbitol pathway to fructose, can also be utilized for the energy metabolism.

Aging↗
PubMedDate not supplied

A selective defect of cytochrome c oxidase is present in brain of Alzheimer disease patients.

To assess mitochondrial function and test the hypothesis of an underlying oxidative phosphorylation defect in Alzheimer disease (AD), we evaluated the activities of mitochondrial respiratory chain enzyme complexes I+III, complexes II+III, complex IV (cytochrome c oxidase, COX), succinate dehydrogenase, and citrate synthase in the frontal cortex, temporal cortex, hippocampus, and cerebellum of 23 AD patients and 13 normal human brains. The major finding was a significant decrease in COX activity in AD temporal cortex and hippocampus, both whether activities were expressed per noncollagen protein content (49 +/-4.6 versus 78+/-10.8 nmol/min/mg NCP, P = 0.006; 23+/-1.9 versus 48.6+/-8.1 nmol/min/mg NCP, p = 0.003) or corrected for citrate synthase activity (1.6+/-0.2 versus 3+/-0.4, P = 0.001; 0.76+/-0.1 versus 1.76+/-0.26, P = 0.0009). There were no significant differences in the activities of complexes I+III, II+III, and of succinate dehydrogenase in any of the brain regions examined. Our results suggest a specific defect of COX in the AD brain versus the normal human brain, which may contribute to impaired energy generation. Biochemically, the defect is confined to selected brain regions, suggesting anatomic specificity.

Aged↗
PubMedDate not supplied

Venous microemboli in patients with artificial heart valves.

BACKGROUND: Detection of microemboli signals (MES) in patients with artificial heart valves has been extensively described, but the underlying material remains unclear. We assumed that the detection of MES in the jugular vein of patients with prosthetic valves would clearly argue for gaseous embolic material, since formed emboli are unable to cross through the capillaries. METHODS AND RESULTS: Twenty-five patients with artificial heart valves, 15 patients with asymptomatic carotid artery disease, and 25 normal controls were examined. Monitoring was performed simultaneously over the dominant jugular vein and the ipsilateral middle cerebral artery for 30 min per subject, using 2-MHz transducers of a color duplex scanner for the jugular vein and a pulsed-wave Doppler for the middle cerebral artery. Data were harvested in an eight-channel digital recorder and MES counts evaluated by two separate observers. MES prevalence in the middle cerebral artery was 100, 13 and 0% in patients with artificial heart valves, asymptomatic carotid artery disease, and normal controls, respectively. No MES were detected in the jugular veins of patients with carotid artery disease or in normal controls, while their prevalence was 68% in patients with artificial heart valves. The interobserver agreement was satisfactory. CONCLUSION: Our results suggest that the embolic material of at least a part of MES in patients with artificial heart valves is gaseous.

Cerebral Arteries↗
PubMedDate not supplied

Carnitine palmitoyltransferase in patients with cardiac ischemia due to atherosclerotic coronary artery disease and in patients with idiopathic dilated cardiomyopathy.

Cardiac ischemia is associated with an impairment in long-chain fatty acid metabolism. We studied carnitine palmitoyltransferase (CPT) in left ventricular biopsies of 6 transplant recipients with ischemia due to atherosclerosis, 4 patients with dilated cardiomyopathy, and 5 donor hearts. Total CPT activity was not significantly different between the three groups (7.9 +/- 3; 6.7 +/- 2, and 8 +/- 3 nmol/min/mg noncollagenous protein). Residual CPT activity after inhibition by malonyl-CoA (0.4 mM) was 38 +/- 11, 36 +/- 5 and 38 +/- 7%. There were no difference in IC50 values. Residual CPT activity after the addition of the detergent Triton X-100 (0.5%) was 58 +/- 17, 54 +/- 2 and 50 +/- 8% (nonsignificant). Our results suggest that (i) total CPT activity and (ii) the sensitivity of the interaction of CPT I with its regulator malonyl-CoA are not affected by cardiac ischemia, and (iii) the ratio of CPT I to CPT II is not altered in cardiac ischemia.

Adult↗
PubMedDate not supplied

Corticomotoneuronal latencies after non-invasive stimulation of the motor cortex in adrenomyeloneuropathy and adrenoleukodystrophy: results in patients and their relatives.

Corticomotoneuronal latencies after non-invasive stimulation of the motor cortex were studied in two patients with adrenomyeloneuropathy (AMN), in one patient with adrenoleukodystrophy (ALD), in two obligate heterozygotes, and in three clinically not affected sisters of the patients with AMN. Corticomotoneuronal latencies were prolonged in the patients as well as in obligate female carriers, but normal in the clinically and biochemically not affected relatives. The noninvasive cortex stimulation was found to be a sensitive method to detect clinical and subclinical deficits in patients and heterozygous carriers.

Adolescent↗