Biomedical subjects

K Jungermann

Publications and source records attributed to K Jungermann.

At least 163 records · Page 9Linked to original sources

PubMed1985

Long-term effects of physiological oxygen concentrations on glycolysis and gluconeogenesis in hepatocyte cultures.

Primary cultures of adult rat hepatocytes were kept for 46 h with either insulin ('insulin cells') or glucagon ('glucagon cells') as the dominant hormone under different oxygen concentrations with 13% (v/v) O2 mimicking arterial and 4% hepatovenous levels. Thereafter metabolic rates were measured for a 2 h period under the same ('overall long-term O2 effects') or a different ('short-term O2 effects') oxygen concentration. From the differences of the two effects the 'intrinsic long-term O2 effects' were derived. Glycolysis, as measured in 'insulin-cells', was stimulated by low O2 levels. It was about threefold faster in cells cultured and tested under 4% O2 as compared to cells cultured and tested under 13% O2, indicating the overall long-term effect. Glycolysis was about twofold faster in cells cultured and tested under 4% O2 as compared to cells cultured under 4% O2 but tested under 13% O2, demonstrating the short-term effect. Glycolysis was about 1.5-fold faster in cells cultured and tested under 4% O2 as compared to cells cultured under 13% O2 but tested under 4% O2, showing the intrinsic long-term effect. This difference was roughly parallel to the difference in levels of glucokinase and pyruvate kinase. Gluconeogenesis, as measured in 'glucagon cells', was stimulated by high O2 levels. Similar to glycolysis overall long-term, short-term and intrinsic long-term effects could be distinguished. The intrinsic long-term effects determined under 13% O2 corresponded to a 1.5-fold stimulation and paralleled the difference in phosphoenolpyruvate carboxykinase levels. The present results show that physiological oxygen concentrations also modulate hepatic carbohydrate metabolism by long-term effects and that the O2 gradient over the liver parenchyma thus contributes to the metabolic differences between periportal and perivenous hepatocytes in vivo.

Animals↗

PubMed1985

[Metabolic zonation of liver parenchyma. Regulation of the glucostat of the liver].

The liver is the glucostat of the organism. It removes glucose when offered in excess as after a normal meal via glycogen synthesis and glycolysis; it provides glucose when needed as in between meals. Hepatocytes from the periportal (afferent) and perivenous (efferent) zones of the liver parenchyma differ in their enzyme content and subcellular structures. Therefore the model of "metabolic zonation" proposes different functions for the two zones. Glucose release is predominantly located in the periportal and glucose uptake in the perivenous zone. The non-zonal, homogeneous and the zonal heterogeneous organization of antagonistic pathways are compared to a narrow country road and a divided highway, respectively, which would allow traffic to proceed at a given time in only one or in both directions, respectively. The highway, corresponding to the model of metabolic zonation, is certainly more efficient than a narrow country road.

Gluconeogenesis↗

PubMed1985

Alteration in the capacities as well as in the zonal and cellular distributions of pyruvate kinase L and M2 in regenerating rat liver.

Pyruvate kinase L (PKL), the glucoregulatory isoenzyme of adult parenchymal cells, and M2 (PKM2), the isoenzyme of proliferating and non-parenchymal cells, were measured, using a specific anti-PKL antibody for differentiation, in total liver homogenates, in isolated parenchymal and non-parenchymal cells as well as in microdissected periportal and perivenous liver tissue from regenerating rat liver after two-thirds partial hepatectomy. Moreover, the zonal distribution of PKL was studied using immunohistochemical techniques. In total liver homogenates PKL activity per g liver decreased after partial hepatectomy, while PKM2 increased. Total PKL activity per 100 g body weight was restored to preoperational levels much more slowly than liver weight. During liver regeneration parenchymal cells acquired high PKM2 besides PKL activity. The isoenzyme outfit of non-parenchymal cells remained unchanged. Microdissection studies showed that PKL lost its normal perivenous to periportal gradient after partial hepatectomy and became evenly distributed within the liver acinus. PKM2 did not retain its even distribution, it became predominant in the periportal zone. Immunohistochemical staining revealed that after partial hepatectomy PKL was present in all parenchymal cells in an atypical non-zonal heterogeneous distribution. Normal specific activities as well as zonal and cellular distributions of both pyruvate kinase isoenzymes were restored 14-21 d after partial hepatectomy. During regeneration after 2/3 partial hepatectomy the liver loses its glucostat function as corroborated in this study by the decrease of the glycolytic capacity via the glucoregulatory PKL; this change of function is accompanied by a loss of PKL-zonation. This finding corroborates the view that zonation of carbohydrate-metabolizing enzymes is required only when the liver functions as a glucostat. The increase of PKM2 and the appearance of a zonal PKM2 heterogeneity are in line with the pattern of hepatocyte proliferation after partial hepatectomy.

Animals↗

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

Control of oxygen uptake, microcirculation and glucose release by circulating noradrenaline in perfused rat liver.

The effect of noradrenaline on oxygen uptake, on periportal and perivenous oxygen tension at surface acini, on microcirculation and on glucose output were studied in isolated rat livers perfused at constant flow with Krebs-Henseleit-hydrogen carbonate buffer containing 5mM glucose and 2mM lactate. Noradrenaline at 1 microM concentration caused a decrease in oxygen uptake, while at 0.1 microM it led to an increase. Both high and low doses of noradrenaline decreased the tissue surface oxygen tension in periportal and - after a transient rise - in perivenous areas. Noradrenaline at an overall constant flow caused an increase of portal pressure and an alteration of the intrahepatic distribution of the perfusate: at the surface of the liver and in cross sections infused trypan blue led to only a slightly heterogeneous staining after a low dose of noradrenaline but to a clearly heterogeneous staining after a high dose. Both high and low doses of noradrenaline stimulated glucose release. All effects could be inhibited by the alpha-blocking agent phentolamine. In conclusion, control of hepatic oxygen consumption by circulating noradrenaline is a complex result of opposing hemodynamic and metabolic components: the microcirculatory changes inhibit oxygen uptake; they dominate after high catecholamine doses. The metabolic effects include a stimulation of oxygen utilization; they prevail at low catecholamine levels. The noradrenergic control of glucose release is also very complex, involving direct, metabolic and indirect, hemodynamic components.

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↗

PubMed1985

Insulin-like action of proinsulin on rat liver carbohydrate metabolism in vitro.

Short-term effects of human proinsulin on metabolic rates and its long-term action on enzyme induction were studied in primary cultures of rat hepatocytes and in the perfused rat liver, and compared with the effects of bovine insulin. In the perfused rat liver, proinsulin decreased the glucagon-dependent increase of glycogenolysis. The action of 0.5 nM glucagon was almost completely suppressed by 100 nM proinsulin. Proinsulin and insulin showed similar potency. In cultured rat hepatocytes, proinsulin stimulated glycolysis up to fivefold with a half-maximal effective dose of 30 nM. Proinsulin induced the key glycolytic enzymes glucokinase and pyruvate kinase by twofold and antagonized the glucagon-dependent induction of phosphoenolpyruvate carboxykinase with a half-maximal effective dose at 3 nM. For the effects in cultured hepatocytes, about 100-fold higher concentrations of proinsulin than of insulin were required.

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

Regulation of peripheral insulin/glucagon levels by rat liver.

The concentrations of insulin and glucagon were measured in the portal and hepatic vein, the abdominal aorta and caval vein in the rat during a normal 24-h feeding cycle. Portal insulin levels showed little diurnal variation while hepatovenous and peripheral values were clearly increased during the eating phase. Conversely, portal glucagon levels were maximal during the fasting period while hepatovenous and peripheral concentrations showed little diurnal variation. The removal of insulin and glucagon by the liver was not constant, but independently regulated. During meals the liver increased the high portal insulin/glucagon ratio further to an even higher peripheral ratio favouring glucose utilization, e.g. by muscle and adipose tissue. During a short fast the liver decreased the low portal insulin/glucagon ratio further to an even lower peripheral ratio leading to glucose saving, e.g. by muscle and adipose tissue in favour of the brain and erythrocytes. The results indicate that the liver has an important role in the regulation of peripheral insulin/glucagon levels.

Animals↗

PubMed1984

Regulation of oxygen consumption and microcirculation by alpha-sympathetic nerves in isolated perfused rat liver.

In isolated rat liver perfused at constant flow with erythrocyte-free Krebs-Henseleit bicarbonate buffer containing 5 mM glucose and 2 mM lactate, perivascular stimulation of the hepatic nerves caused a rapid decrease of oxygen uptake, a decrease of the periportal and, after a transient rise, of the perivenous tissue po2 of surface acini, an increase of portal pressure, and an enhancement of glucose output. Furthermore, nerve stimulation changed the intrahepatic distribution of the perfusate drastically. Infusion of trypan blue 20 s after nerve stimulation resulted in a heterogeneous staining of the liver both at the surface and in cross-sections, while it led to a homogeneous distribution in non-stimulated controls. It is concluded that the major component in the mechanism of the nerve-dependent decrease of oxygen uptake is the microcirculatory change rather than a metabolic effect.

Animals↗

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↗

PubMed1984

Regulation of oxygen consumption in perfused rat liver: decrease by alpha-sympathetic nerve stimulation and increase by the alpha-agonist phenylephrine.

In livers perfused with Krebs-Henseleit bicarbonate buffer containing bovine red cells, 5 mM glucose and 2 mM lactate, electrical stimulation round the hepatic artery and the portal vein caused via alpha-receptors a decrease in oxygen consumption and portal flow, an increase in glucose output and a switch from lactate uptake to output. In livers perfused with erythrocyte- and substrate-free buffer both in a volume- or pressure-constant system stimulation of the liver nerves resulted in similar changes. Infusion of the alpha-agonist phenylephrine mimicked the metabolic and hemodynamic nerve effects, but led to an increase in oxygen uptake. The converse effects of alpha-sympathetic nerve stimulation and alpha-agonist infusion on oxygen consumption indicate either a different mode of action or a complex mechanism with opposing metabolic and hemodynamic components.

Animals↗

PubMed1983

Short-term modulation of glycogen metabolism, glycolysis and gluconeogenesis by physiological oxygen concentrations in hepatocyte cultures.

The influence of different oxygen concentrations (0% to 20%, v/v) on the main pathways of carbohydrate metabolism was studied in rat hepatocyte cultures. Cells resembling the periportal or the perivenous cell type were obtained after 48 h culture under different hormonal conditions; they are referred to as 'periportal' or 'perivenous', respectively. Using radiochemical techniques the metabolic rates of the two cell types were measured between 48 h and 50 h under different oxygen tensions. Standard physiological substrates of 5 mM glucose, 2 mM lactate and endogenous glycogen were used. In cells incubated under 4% O2, mimicking hepatovenous oxygen levels, compared to cells assayed under 13% O2, mimicking arterial levels, glycogen degradation to free glucose and to lactate was faster while glycogen synthesis was slower; glycolysis, from glucose to lactate, was faster and gluconeogenesis, from lactate to glucose, was only slightly slower. Under anoxic conditions glycogen breakdown was maximal and glycogen synthesis minimal; gluconeogenesis was also minimal, but glycolysis was not maximal, it reached its peak rate at 4% O2. CO2-formation increased up to 6% and then stayed essentially constant at higher O2 tensions. Net glycogen metabolism: in 'perivenous' cells net glycogen synthesis was observed above, net glycogen degradation below 4% O2. In 'periportal' cells, which had a very low glycogen content, net glycogen metabolism was very small. Net glucose metabolism: in 'perivenous' cells net glucose formation was only seen under anoxic conditions. Net glucose utilization was observed at about the same rate under all physiological O2 tensions. In 'periportal' cells net glucose formation increased clearly up to 6% O2 and then remained almost constant. Net lactate metabolism: in 'perivenous' cells net lactate formation occurred below, and net lactate utilization above, 6% O2. In 'periportal' cells a pronounced net lactate utilization was observed under all physiological O2 tensions. Net flow between glucose-6-phosphate and pyruvate was observed in the glycolytic direction in 'perivenous' and in the gluconeogenic direction in 'periportal' cells except under anoxic conditions. When O2 tensions were lowered, the percentage of 'futile cycling' was decreased in the 'perivenous', glycolytic hepatocytes; conversely, it was increased in the 'periportal', gluconeogenic hepatocytes. It is concluded that physiological oxygen concentrations modulate hepatic carbohydrate metabolism and that they contribute further to the proposed metabolic differences between periportal and perivenous cells in vivo.

Animals↗

PubMed1983

Short-term regulation of glycolysis by insulin and dexamethasone in cultured rat hepatocytes.

Evidence for a direct metabolic effect of insulin in isolated liver preparations is scarce. The stimulation of glycolysis by insulin previously demonstrated in monolayer cultures of adult rat hepatocytes [(1982) Eur. J. Biochem. 126, 271-278] was further investigated. The degree of stimulation varied with the age of the culture and amounted to 250%, 200%, 500% and 200% of the control value using cells at the culture age of 2 h, 24 h, 48 h, and 72 h, respectively. Half-maximal dose of insulin was 0.1 nM. Maximal stimulation was reached within 5 min and lasted for at least 4 h. Dexamethasone acted both as a long-term and short-term modulator. Long-term pretreatment of the cells with dexamethasone proved necessary to permit insulin action. In addition to this permissive action, pretreatment with dexamethasone reduced the insulin-independent basal glycolytic rate. In short-term experiments dexamethasone decreased the basal glycolytic flux, however, it did not affect the absolute increase in glycolysis brought about by insulin. The half-maximal dose of dexamethasone was 10 nM. The stimulatory effects of insulin may in part be attributed to the activation of pyruvate kinase. Insulin produced a left-shift of the substrate saturation curve, decreasing the K0.5 value for phosphoenolpyruvate.

Animals↗

PubMed1983

Functional significance of hepatocyte heterogeneity for glycolysis and gluconeogenesis.

Hepatocytes from the periportal (afferent) and perivenous (efferent) zone of the liver parenchyma differ in their enzyme distribution and subcellular structures. The key enzymes of gluconeogenesis are predominant in the periportal zone, those of glycolysis in the perivenous zone. The heterogeneous expression of the genome in hepatocytes is apparently caused by the periportal to perivenous gradient in oxygen- and hormone-concentrations as well as by a different autonomic innervation of the parenchymal zones. The model of "metabolic zonation" suggests that, in concordance with the distribution of the key enzymes, gluconeogenesis would be predominantly catalyzed by periportal hepatocytes, while glycolysis would be preferentially mediated by perivenous cells. This model is corroborated by a calculation of the flux at the glucose/glucose-6-phosphate cycle in vivo in the periportal and perivenous zone and by a determination of the glycolytic and gluconeogenic rate in "periportal" and "perivenous" hepatocytes induced in cell culture.

Blood Glucose↗

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

The glucagon-insulin antagonism and glucagon-dexamethasone synergism in the induction of phosphoenolpyruvate carboxykinase in cultured rat hepatocytes.

In hepatocytes precultured for 24 h with dexamethasone glucagon increased phosphoenolpyruvate carboxykinase activity 3-4-fold with a half maximal activity increase at 30 pM. The half maximal effective glucagon concentration was enhanced 10-fold to 300 pM when insulin was added simultaneously. The glucagon-insulin antagonism was maximally expressed when glucagon was present at low physiological concentrations. At equimolar doses it was only in the concentration range around 0.1 nM that glucagon and insulin became powerful antagonists; at higher levels glucagon was the dominant hormone. In hepatocytes not pretreated with dexamethasone glucagon still enhanced phosphoenolpyruvate carboxykinase activity, but the half maximal effective dose raised more than 30-fold to 1 nM. The degree of stimulation, however, remained essentially unchanged. Thus dexamethasone shifted the glucagon sensitivity of the cells into the physiological concentration range; it exerted a half maximal effect at 10 nM. Dexamethasone was not required for the enzyme induction proper if the cells had been pretreated with the glucocorticoid. The amount of the glucagon-stimulated enzyme induction was dependent on the time period of cell pretreatment with dexamethasone. Glucagon enhanced enzyme activity to the same constant suboptimal level irrespective of whether cells had been pretreated with glucocorticoid for 1 or for 14 h. If cells were pretreated for more than 15 h, glucagon linearly increased enzyme activity further until the maximal value was reached after 24 h pretreatment. The glucagon-insulin antagonism and the glucagon-glucocorticoid synergism were observed at physiological hormone concentrations indicating that the interaction should be effective also in vivo. Dexamethasone does not seem to be generally permissive for the inducing action of glucagon, but rather sensitizes the cell towards lower physiological hormone concentrations.

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↗