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Biomedical subjects

E Sutherland

Publications and source records attributed to E Sutherland.

At least 19 recordsLinked to original sources
PubMed1998

A high-sucrose diet alters the lipid composition and fluidity of liver sinusoidal membranes.

Impaired insulin suppression of hepatic glucose production and accumulation of hepatic triglycerides occur after 1 week on a high-sucrose diet. The purpose of this study was to ascertain whether changes in structural lipids, fatty acid composition and/or fluidity occur after 1 week on a high-sucrose diet, and therefore might contribute to the sucrose-induced impairment in hepatic glucose metabolism. Male Wistar rats (n=28) were fed a purified high starch (68% of energy) diet for a 2-week baseline period. Fourteen animals were then switched to a high sucrose (68% of energy) diet for 1 (n=7) or 5 (n=7) weeks. Analyses were performed on liver sinusoidal membranes (due to this membrane's involvement in nutrient transport) from overnight fasted rats. The degree of saturation of sinusoidal membrane phospholipids and liver triglyceride fatty acids was significantly greater in sucrose vs. starch at 1 and 5 weeks. This resulted in significantly lower sinusoidal membrane fluidity at 1 and 5 weeks in the sucrose group. In contrast, hepatic sinusoidal membrane cholesterol content (0.60+/-0.05 vs. 0.42+/-0.04 micromol/mg protein) and the cholesterol to phospholipid molar ratio (0.66+/-0.04 vs. 0.50+/-0.03) were significantly greater in sucrose vs. starch animals at 5 weeks only. Minimal differences were observed in individual phospholipid species between groups. These data suggest that changes in fatty acid composition and fluidity may contribute to the development of sucrose-induced hepatic insulin resistance.

Animals↗
PubMed1996

Increased hepatic Na,K-ATPase activity during hepatic regeneration is associated with induction of the beta1-subunit and expression on the bile canalicular domain.

Cellular and molecular mechanisms regulating the activity of the sodium pump or Na,K-ATPase during proliferation of hepatocytes following 70% liver resection have not been defined. Na,K-ATPase may be regulated by synthesis of its alpha- and beta-subunits, by sorting to either the sinusoidal or apical plasma membrane domains, or by increasing membrane lipid fluidity. This study investigated the time course of changes during hepatic regeneration for Na, K-ATPase activity, lipid composition and fluidity, and protein content of liver plasma membrane subfractions. As early as 4 h after hepatic resection, Na,K-ATPase activity was increased selectively in the bile canalicular fraction. It reached a new steady state at 12 h and remained elevated for 2 days. Although hepatic regeneration was associated with a reduced cholesterol/phospholipid molar ratio and increased fluidity, measured with two different probes, these changes in lipid metabolism were in the sinusoidal membrane domain. The Na,K-ATPase beta1-subunit, but not the alpha1-subunit, was increased selectively at the bile canalicular surface as shown by immunoblotting of liver plasma membrane subfractions and the morphological demonstration at both the light and electron microscopic levels. Furthermore, cycloheximide blocked the rise in beta1-subunit mRNA levels. Since the time course for beta1-subunit accumulation was similar to that for activation of Na,K-ATPase activity, this change implicated the beta1-subunit in activating sodium pump activity.

Animals↗
PubMed1996

Ethinyl estradiol cholestasis involves alterations in expression of liver sinusoidal transporters.

The mechanisms involved in ethinyl estradiol-induced cholestasis are controversial. Basal bile flow was reduced by ethinyl estradiol administration, with a half time (t1/2) of 12.5 +/- 0.6 h. In contrast, initial taurocholate uptake was not significantly reduced until 3 days to 59% of control and to 13 and 10% of control at 5 and 7 days, respectively. The t1/2 was 4.3 +/- 0.1 days. These physiological changes were correlated with measurement of protein mass and steady-state mRNA for Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase), Na(+)-dependent taurocholate transporter, organic anion transporters, and membrane lipid fluidity. Ethinyl estradiol significantly decreased Na(+)-K(+)-ATPase activity and membrane fluidity. However, neither Na(+)-K(+)-ATPase alpha-subunit nor beta-subunit mass was altered by ethinyl estradiol administration. In contrast, protein content of the Na(+)-dependent taurocholate transporter was significantly reduced to 21% of control (P < 0.001) at 5 days. The Na(+)-dependent taurocholate transporter was identified in sinusoidal membrane fractions as a doublet with a molecular size estimated to be 51 and 56 kDa. Although both bands were reduced with ethinyl estradiol treatment, the 56-kDa band was decreased more rapidly and to a greater extent than the 51-kDa band. The estimated t1/2 of 4.8 +/- 0.6 days for the doublet was similar to that for Na(+)-dependent taurocholate uptake. The organic anion transporter protein mass was similarly reduced with time of ethinyl estradiol administration to 21% of control (P < 0.01) at 5 days. Ethinyl estradiol also rapidly decreased the steady-state mRNA levels of Na(+)-dependent and organic anion transporters to approximately 50% and 15% of control at 5 days, respectively. These studies indicate early generalized abnormalities of the sinusoidal membrane lipid fluidity, Na(+)-K(+)-ATPase activity, and bile acid transport protein content.

Animals↗
PubMed1995

Hepatic Na(+)-K(+)-ATPase enzyme activity correlates with polarized beta-subunit expression.

We have examined underlying causes for observations made in hepatocytes in which catalytic subunits of Na(+)-K(+)-ATPase are found both in bile canalicular (apical) and sinusoidal (basolateral) membrane domains, whereas functional activity is associated preferentially with sinusoidal membrane sites. In a series of parallel studies, we determined by both light and electron microscopy that Na(+)-K(+)-ATPase alpha-subunits were localized to both membrane domains of hepatocytes. With the use of purified liver plasma membrane subfractions, ouabain inhibition curves demonstrated similar inhibition constants (inhibition constant 10(-5) M), and immunoblots using alpha 1-, alpha 2-, and alpha 3-polyclonal and monoclonal antibodies demonstrated antigenic sites predominantly for alpha 1 in both membrane fractions. Also, Northern blot hybridization analysis revealed only the alpha 1-isoform in hepatocytes. In contrast to the bipolar distribution of the alpha 1-subunit, the beta-subunit was identified only at the sinusoidal surface using fluorescence labeling with a monoclonal antibody. The beta 1-isoform was demonstrated by Northern blot analysis and was present predominantly at the sinusoidal domain by immunoblotting with polyclonal antibodies. In addition to the bipolar distribution of alpha 1, immunoblotting of liver plasma membrane subfractions demonstrated a symmetrical distribution of fodrin, ankyrin, actin, and E-cadherin at both domains. These results suggest that functionally competent alpha/beta-complexes form at the sinusoidal domain, whereas only alpha 1-subunits are present at the apical pole.

Animals↗
PubMed1993

Distribution of adenylate cyclase and GTP-binding proteins in hepatic plasma membranes.

Hepatic membrane subfractions prepared from control rats demonstrated forskolin (FSK)-stimulated adenylate cyclase activity in the basolateral (sinusoidal) but not apical (canalicular) plasma membrane. After bile duct ligation (BDL) for 12 or 24 h, there was an increase in FSK-stimulated adenylate cyclase activity in the apical membrane (54.2 +/- 3.9 pmol.mg-1 x min-1). The mechanism for this increase was explored further. ATP hydrolysis was found to be much higher in the apical than the basolateral membrane. Increasing the ATP levels in the assay enhanced apical membrane adenylate cyclase activity (10.5 +/- 0.2 pmol.mg-l.min-1); however, total adenosinetriphosphatase (ATPase) activity was not altered after BDL. Extraction of the apical membrane with bile acids or other detergents resulted in a two- to threefold increase in adenylate cyclase activity (30.6 +/- 3.6 pmol.mg-1 x min-1; detergent C12E8) This suggested that bile duct ligation was acting via the detergent-like action of bile acids to uncover latent adenylate cyclase activity on apical membranes. Further studies demonstrated that both BDL and detergent extraction also enhanced toxin-directed ADP-ribosylation of Gs alpha (cholera toxin) and Gi alpha (pertussis toxin) in the apical but not the basolateral membrane. After BDL, Gi alpha was found to be twofold greater in the apical membrane than the basolateral membrane. Immunoblotting using specific G protein antibodies further confirmed that apical membranes from control rats had a higher concentration of Gi1, 2 alpha and beta and slightly elevated levels of Gi3 alpha and Gs alpha compared with the basolateral membrane. The results demonstrate that adenylate cyclase and heterotrimeric GTP-binding proteins are present on the apical membrane, but measurement of their functional activity requires detergent permeabilization of apical membrane vesicles and is limited by the presence of high ATPase activity.

Adenosine Triphosphatases↗
PubMed1992

McrBC: a multisubunit GTP-dependent restriction endonuclease.

McrBC-mediated restriction of modified DNA has been studied extensively by genetic methods, but little is known of its molecular action. We have used overproducing plasmid constructs to facilitate purification of the McrBL and McrC proteins, and report preliminary characterization of the activity of the complex. Both proteins are required for cleavage of appropriately modified DNA in vitro, in a reaction absolutely dependent on GTP. ATP inhibits the reaction. The sequence and modification requirements for cleavage of the substrate reflect those seen in vivo. The position of cleavage was examined at the nucleotide level, revealing that cleavage occurs at multiple positions in a small region. Based upon these observations, and upon cleavage of model oligonucleotide substrates, it is proposed that the recognition site for this enzyme consists of the motif RmC(N40-80)RmC, with cleavage occurring at multiple positions on both strands, between the modified C residues. In subunit composition, cofactor requirement, and relation between cleavage and recognition site, McrBC does not fit into any of the classes (types I to IV) of restriction enzyme so far described.

Adenosine Triphosphate↗
PubMed1992

Forebrain ischemia in diabetic and nondiabetic BB rats studied with 31P magnetic resonance spectroscopy.

In spontaneously diabetic BB rats, the effect of chronically maintained blood glucose levels on the degree of energy failure and brain pH change during an ischemic insult, and on subsequent recovery after reperfusion, was studied with in vivo 31P magnetic resonance spectroscopy. Short duration forebrain ischemia (10-min carotid occlusion plus hypotension of 50 mmHg) was induced in diabetic and nondiabetic male BB rats whose blood glucose levels were maintained with insulin. Spectra were obtained in 1-min blocks before, during, and for 1 h after ischemia. Before ischemia, hypoglycemic (blood glucose less than 3 mM) diabetic rats had an increased Pi peak intensity, with no significant pH change, compared with other groups. During ischemia, the rate and extent of hydrolysis of high-energy phosphate metabolites (as measured by an increase in Pi) decreased, and the severity of tissue acidosis increased as preischemia blood glucose concentration increased. Among hyperglycemic BB rats, similar ischemia-induced changes were found for subgroups with blood glucose levels of 13.7 +/- 1.2 and 20.3 +/- 0.6 mM, in keeping with the known decrease in hexose binding sites associated with chronic hyperglycemia. Decline in PCr level during ischemia was not significantly different between groups. With reperfusion, both Pi and pH values rapidly returned to preischemia values. PCr levels, however, did not recover in hyperglycemic diabetic animals, with the degree of residual impairment dependent on the preischemia glucose level. Results suggest that optimal management of diabetes may lessen the degree of injury within the ischemic penumbra in diabetic patients who suffer a stroke.

Analysis of Variance↗
PubMed1992

CircumVent thermal cycle sequencing and alternative manual and automated DNA sequencing protocols using the highly thermostable VentR (exo-) DNA polymerase.

CircumVent thermal cycle and standard DNA sequencing protocols utilizing the cloned and highly thermostable VentR (exo-) DNA polymerase are described. The thermal cycle sequencing procedures are advantageous because they allow fast and simple semiautomation of the sequencing reaction; make possible the direct DNA sequencing of PCR products, bacterial colonies and phage plaques; require only femtomoles of template DNA; eliminate the requirement of an independent primer annealing step; remove the requirement of denatured plasmids for sequencing double-stranded templates; and use a highly thermostable DNA polymerase for sequencing through potential recalcitrant secondary structure domains and large linear double-stranded DNA templates such as lambda derivatives. More standard methods of DNA sequencing (i.e., a one-step protocol and a labeling-termination protocol) are also presented. For each protocol, alternatives for choice of label and method of labeling are presented, including the use of 5' biotinylated primers for chemiluminescent DNA sequencing and fluorinated primers for automated sequencing using the BaseStation Automated DNA Sequencer.

Autoradiography↗
PubMed1990

Genetic and sequence organization of the mcrBC locus of Escherichia coli K-12.

The mcrB (rglB) locus of Escherichia coli K-12 mediates sequence-specific restriction of cytosine-modified DNA. Genetic and sequence analysis shows that the locus actually comprises two genes, mcrB and mcrC. We show here that in vivo, McrC modifies the specificity of McrB restriction by expanding the range of modified sequences restricted. That is, the sequences sensitive to McrB(+)-dependent restriction can be divided into two sets: some modified sequences containing 5-methylcytosine are restricted by McrB+ cells even when McrC-, but most such sequences are restricted in vivo only by McrB+ McrC+ cells. The sequences restricted only by McrB+C+ include T-even bacteriophage containing 5-hydroxymethylcytosine (restriction of this phage is the RglB+ phenotype), some sequences containing N4-methylcytosine, and some sequences containing 5-methylcytosine. The sequence codes for two polypeptides of 54 (McrB) and 42 (McrC) kilodaltons, whereas in vitro translation yields four products, of approximately 29 and approximately 49 (McrB) and of approximately 38 and approximately 40 (McrC) kilodaltons. The McrB polypeptide sequence contains a potential GTP-binding motif, so this protein presumably binds the nucleotide cofactor. The deduced McrC polypeptide is somewhat basic and may bind to DNA, consistent with its genetic activity as a modulator of the specificity of McrB. At the nucleotide sequence level, the G+C content of mcrBC is very low for E. coli, suggesting that the genes may have been acquired recently during the evolution of the species.

Amino Acid Sequence↗
PubMed1990

Identification of taurocholate binding sites in ileal plasma membrane.

Intestinal absorption of bile salts occurs by passive processes throughout the length of the small intestine, whereas active carrier-mediated uptake is localized to the ileum. Although previous studies have extensively characterized brush-border transport of bile acids, their extrusion across the basolateral membrane is less well understood. Because previous reports had failed to show specific bile acid binding sites except with the use of photolabeled bile salt derivatives, we sought to identify and characterize the binding parameters of the physiological bile salt taurocholate in ileal and jejunal plasma membrane subfractions. Brush-border membrane (BBM) and basolateral membrane (BLM) fractions were rapidly and simultaneously isolated from the small intestinal mucosa. BBM fractions were isolated with enrichments of 50- to 54-fold for leucine aminopeptidase, whereas the basolateral membrane enrichment of Na(+)-K(+)-ATPase, its specific marker enzyme, was 22- to 25-fold. Contamination from intracellular organelles was minimal. Binding of [14C]taurocholate was demonstrated in both jejunal as well as ileal plasma membrane fractions. However, only ileal binding demonstrated saturation, reversibility, and susceptibility to proteolytic enzymes. [14C]taurocholate binding to BBM fractions also showed competition with bile acids but was not altered by pH or alkylating agents. In contrast, binding of taurocholate to the basolateral membrane showed optimal pH between 6.5 and 7.5 and was inhibited by thiol and alkylating agents. Kinetic analysis of specific ileal BBM and BLM binding showed the parameters for BBM as 288 +/- 70 microM and 2.4 +/- 0.6 nmol/mg protein and for BLM as 6.6 +/- 0.7 microM and 0.56 +/- 0.01 nmol/mg protein for dissociation constant and maximum binding capacity, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Forebrain ischemia studied using magnetic resonance imaging and spectroscopy.

A combination of magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) has been used to follow the time course of changes resulting from forebrain ischemia in the rat. The 31P MRS demonstrates that the level of high energy metabolites decreases significantly during the 10 min ischemic period but returns to normal after 1 h of reperfusion. MRI shows no change after 1 h of reperfusion but significant changes in the striatum after 24 h and in the hippocampus after 48 h. These changes correlate well with histopathology. Diabetic rats have shown the effect of hyperglycemia in accentuation of ischemic and post ischemic pH changes. Conversely, diabetic rats maintained severely hypoglycemic with insulin showed little variation in pH during or following the ischemic insult. The results emphasize the importance of both MRS and MRI in following the temporal profile and distribution of ischemic neuronal injury.

Animals↗
PubMed1989

Bradykinin activates protein kinase C in cultured cortical collecting tubular cells.

Bradykinin inhibits vasopressin-stimulated water transport in cortical collecting tubular cells. The biochemical mechanism of this effect was explored by means of primary cultures of rabbit cortical collecting tubular cells. Bradykinin was found to produce a rapid release of calcium from intracellular stores, an increase in sn-1,2-diacylglycerol levels, and a fivefold increase in membrane-bound protein kinase C activity, consistent with stimulation of phospholipase C and activation of protein kinase C in rabbit cortical collecting tubular cells. In addition, bradykinin produced a dose-dependent 46% inhibition of vasopressin-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) formation. Pretreatment with the protein kinase C inhibitors, H-7 and staurosporine, reversed the bradykinin-mediated inhibition of vasopressin-stimulated cAMP accumulation. In contrast, pretreatment with either the phospholipase A2 inhibitor, mepacrine, or pertussis toxin did not prevent the inhibitory effect of bradykinin on vasopressin-stimulated cAMP production, suggesting that the effects are not mediated by prostaglandin E2 or activation of a pertussis-toxin sensitive guanine nucleotide regulatory protein (e.g., Gi). Because bradykinin also inhibits isoproterenol-stimulated cAMP formation but does not inhibit either basal-, forskolin-, or cholera toxin-stimulated cAMP accumulation, the site of this inhibition appears to involve the hormone receptor or coupling of the receptor to the stimulatory guanine nucleotide regulatory subunit (Gs). The results demonstrate that bradykinin stimulates phospholipase C leading to activation of protein kinase C, which then inhibits vasopressin-stimulated cAMP production at the level of the hormone receptor or coupling of the receptor to Gs in cultured cortical collecting tubular cells.

Animals↗
PubMed1988

Ethinylestradiol administration selectively alters liver sinusoidal membrane lipid fluidity and protein composition.

Administration of high-dose ethinylestradiol to rats decreases bile flow, Na,K-ATPase specific activity, and liver plasma membrane fluidity. By use of highly purified sinusoidal and bile canalicular membrane fractions, the effect of ethinylestradiol administration on the protein and lipid composition and fluidity of plasma membrane fractions was examined. In sinusoidal fractions, ethinylestradiol (EE) administration decreased Na,K-ATPase activity (32%) and increased activities of alkaline phosphatase (254%), Mg2+-ATPase (155%), and a 160-kDa polypeptide (10-fold). Steady-state and dynamic fluorescence polarization was used to study membrane lipid structure. Steady-state polarization of diphenylhexatriene (DPH) was significantly higher in canalicular compared to sinusoidal membrane fractions. Ethinylestradiol (5 mg/kg per day for 5 days) selectively increased sinusoidal polarization values. Similar changes were demonstrated with the probes 2- and 12-anthroyloxystearate. Time-resolved fluorescence polarization measurements indicated that EE administration for 5 days did not change DPH lifetime but increased the order component (r infinity) and decreased the rotation rate (R). However, 1 and 3 days after EE administration and with low doses (10-100 micrograms/kg per day for 5 days) the Na,K-ATPase, bile flow, and order component were altered, but the rotation rate was unchanged. Vesicles prepared from total sinusoidal membrane lipids of EE-treated rats, as well as phospholipid vesicles, demonstrated increased DPH polarization, as did intact plasma membrane fractions. Liver plasma membrane fractions showed no change in free cholesterol or cholesterol/phospholipid molar ratio, while esterified cholesterol content was increased with high-dose but not low-dose ethinylestradiol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Biochemical localization of hepatic surface-membrane Na+,K+-ATPase activity depends on membrane lipid fluidity.

Membrane proteins of transporting epithelia are often distributed between apical and basolateral surfaces to produce a functionally polarized cell. The distribution of Na+,K+-ATPase [ATP phosphohydrolase (Na+/K+-transporting), EC 3.6.1.37] between apical and basolateral membranes of hepatocytes has been controversial. Because Na+,K+-ATPase activity is fluidity dependent and the physiochemical properties of the apical membrane reduces its fluidity, we investigated whether altering membrane fluidity might uncover cryptic Na+,K+-ATPase in bile canalicular (apical) surface fractions free of detectable Na+,K+-ATPase and glucagon-stimulated adenylate cyclase activities. Apical fractions exhibited higher diphenylhexatriene-fluorescence polarization values when compared with sinusoidal (basolateral) membrane fractions. When 2-(2-methoxyethoxy)ethyl 8-(cis-2-n-octylcyclopropyl)octanoate (A2C) was added to each fraction, Na+,K+-ATPase, but not glucagon-stimulated adenylate cyclase activity, was activated in the apical fraction. In contrast, further activation of both enzymes was not seen in sinusoidal fractions. The A2C-induced increase in apical Na+,K+-ATPase approached 75% of the sinusoidal level. Parallel increases in apical Na+,K+-ATPase were produced by benzyl alcohol and Triton WR-1339. All three fluidizing agents decreased the order component of membrane fluidity. Na+,K+-ATPase activity in each subfraction was identically inhibited by the monoclonal antibody 9-A5, a specific inhibitor of this enzyme. These findings suggest that hepatic Na+,K+-ATPase is distributed in both surface membranes but functions more efficiently and, perhaps, specifically in the sinusoidal membranes because of their higher bulk lipid fluidity.

Animals↗
PubMed1988

Selective modulation of hepatic and ileal Na+-K+-ATPase by bile salts in the rat.

Sodium-potassium adenosinetriphosphatase (Na+-K+-ATPase) is modulated by functional demands. We determine whether Na+-K+-ATPase specific activity was changed by oral administration of different bile salts and whether upregulation in the liver is due to increased numbers of catalytic units. In rats after bile duct drainage for 18 h, Na+-K+-ATPase activity was reduced to 50% of control in liver and ileum but unchanged in jejunum and kidney. Increased Na+-K+-ATPase activity after short-term feeding of bile salts was noted only following trihydroxy bile salts, i.e., taurocholate (100 mg/100 g body wt) increased hepatic Na+-K+-ATPase 143% and ileum 138% above control, whereas jejunum and kidney were unchanged. Chronic feeding of trihydroxy bile salts for 4 days increased hepatic Na+-K+-ATPase (214-260%) and alkaline phosphatase (189-274%), whereas 5'-nucleotidase and Mg2+-ATPase activities were unchanged from control. Plasma membrane Na+-K+-ATPase activity significantly increased as early as 4 h after taurocholate administration, whereas homogenate activity did not rise until 16 h; both reached a new steady state between 24 and 48 h. Sixteen hours after bile salt feeding, increased Na+-K+-ATPase activity was blocked by cycloheximide, and in the liver increased enzyme activity (179%) was associated with a comparable change in sodium-dependent [gamma-32P]ATP binding (162%) to liver plasma membrane fractions. These studies show Na+-K+-ATPase activity adapts selectively in liver and ileum following administration of trihydroxy bile salts, and the process involves increased density of Na+-K+ pump sites on the liver plasma membrane.

Animals↗
PubMed1987

Patterns of porphyrin accumulation in response to xenobiotics. Parallels between results in chick embryo and rodents.

Our objective was to determine whether patterns of porphyrin accumulation produced by chemicals in chick embryo hepatocyte culture would indicate which enzyme of heme biosynthesis was inhibited. The ferrochelatase-inhibitory potency and porphyrin patterns produced by DDC, TTMS, and their analogues were studied. The protoporphyrin:coproporphyrin ratio observed was found to correlate with ferrochelatase-inhibitory activity. The results obtained in chick embryo with TTMS and DDC parallel those found in rodents. Griseofulvin has been shown to lower ferrochelatase activity and to cause the accumulation of protoporphyrin in rodent liver. In chick embryo liver cell culture, however, coproporphyrin, uroporphyrin, and heptacarboxylic acid porphyrin accumulate and ferrochelatase activity is not lowered. Uroporphyrin, heptacarboxylic acid porphyrin, and coproporphyrin are the major porphyrins to accumulate in response to PAHs (for example, 3,3',4,4'-TCBP in chick embryo liver cell culture). This may be explained by inhibition of UROD, which has been observed in chick embryo and rodent liver. Some chemicals, such as phenobarbital and nifedipine, cause the accumulation of these porphyrins in chick embryo liver cell culture, and this is explained by inhibition of UROD. These chemicals have not been reported to interfere with heme biosynthesis in the intact chick embryo or rodents; possibly protective mechanisms that are not available in the cell culture system are operative in the intact animal. It was concluded that porphyrin patterns may serve as a guide to which enzyme of heme biosynthesis is inhibited in chick embryo liver cell culture. The results obtained in the culture system with certain chemicals, such as DDC and TTMS analogues and PAHs, correspond with results in rodents. In other cases, such as with griseofulvin, the results do not correspond.

5-Aminolevulinate Synthetase↗