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PubMed1985

A milder variant of Zellweger syndrome.

A 4.5-year-old male patient is described with chorioretinopathy, minor facial anomalies, delayed closure of the fontanel, mental retardation, moderate hypotonia, epilepsy and hepatic fibrosis. Postural control, intentional vocalising and manual dexterity were superior to the performance of patients with classical Zellweger syndrome (ZS). Morphologically distinct peroxisomes were absent in the liver. In blood elevated pipecolic acid levels and abnormal levels of bile acid intermediates were found. The plasmalogen content of erythrocytes was normal. In fibroblasts we found an accumulation of very long chain fatty acids, decreased activity of acyl CoA:dihydroxyacetone phosphate acyltransferase, and impaired de novo biosynthesis of plasmalogens. On the basis of these clinical, ultrastructural and biochemical characteristics we assume that this patient represents a milder variant of the classical cerebro-hepato-renal syndrome of Zellweger.

Abnormalities, Multiple↗

PubMed2002

A novel near-infrared fluorescence sensor for detection of thrombin activation in blood.

Thrombosis is an important pathophysiologic component of many cardiovascular diseases. Thrombin, a serine protease, plays a central role in thrombosis formation. Detection and imaging of thrombin activity may thus be of considerable biomedical interest. The goal of this study was to design, synthesize, and characterize a novel thrombin-activated near-infrared fluorescence (NIRF) probe. The probe consisted of a thrombin-cleavable peptide spacer (...D-Phe-Pip-Arg...; Pip=pipecolic acid) and contained a terminal fluorescence reporter which was quenched when conjugated to a biocompatible delivery vehicle. A control peptide spacer was synthesized that differed by one amino acid. Following thrombin addition, the probe was activated within minutes. The NIRF signal increased by a factor of 27-fold within 20 minutes, and was inhibited by hirudin, a specific thrombin inhibitor. NIRF optical imaging experiments confirmed rapid activation of the probe in both buffer and human blood. The control probe showed minimal activation in all experiments. In addition to potentially furthering our understanding of thrombin regulation in vivo, the thrombin-activated near-infrared probe may have broad clinical application to the diagnosis of arterial and venous thrombosis.

Enzyme Activation↗

PubMed2006

Pyridoxine-dependent seizures in Dutch patients: diagnosis by elevated urinary alpha-aminoadipic semialdehyde levels.

BACKGROUND: Pyridoxine-dependent seizures (PDS) is a rare, autosomal recessively inherited disorder. Recently alpha-aminoadipic semialdehyde (alpha-AASA) dehydrogenase deficiency was identified as a major cause of PDS, which causes accumulation of both alpha-AASA and pipecolic acid (PA) in body fluids. METHODS: We studied urinary and plasma alpha-AASA and PA levels in 12 Dutch clinically diagnosed patients with PDS. RESULTS: Alpha-AASA was elevated in both urine and plasma in 10 patients. In these patients plasma PA levels were also elevated but urinary PA levels were normal. DISCUSSION: In all patients with clinically definite PDS, and in most patients with probable or possible PDS, the clinical diagnosis of PDS could be confirmed at the metabolite level. Non-invasive urinary screening for alpha-AASA accumulation provides a reliable tool to diagnose PDS and can save these patients from the classical and potentially dangerous pyridoxine withdrawal test to prove PDS.

Aldehyde Dehydrogenase↗

PubMed2002

Synthesis of N-glyoxyl prolyl and pipecolyl amides and thioesters and evaluation of their in vitro and in vivo nerve regenerative effects.

The recent discovery that small molecule ligands for the peptidyl-prolyl isomerase (PPIase) FKBP12 possess powerful neuroprotective and neuroregenerative properties in vitro and in vivo suggests therapeutic utility for such compounds in neurodegenerative disease. The neurotrophic effects of these compounds are independent of the immunosuppressive pathways by which drugs such as FK506 and rapamycin operate. Previous work by ourselves and other groups exploring the structure-activity relationships (SAR) of small molecules that mimic only the FKBP binding domain portion of FK506 has focused on esters of proline and pipecolic acid. We have explored amide and thioester analogues of these earlier structures and found that they too are extremely potent in promoting recovery of lesioned dopaminergic pathways in a mouse model of Parkinson's disease. Several compounds were shown to be highly effective upon oral administration after lesioning of the dopaminergic pathway, providing further evidence of the potential clinical utility of a variety of structural classes of FKBP12 ligands.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1972

Effect of the proline analogue baikiain on proline metabolism in Salmonella typhimurium.

A proline analogue, 4,5-dehydro-l-pipecolic acid (baikiain) induces the formation in Salmonella typhimurium of the two enzymes catalyzing the degradation of proline, proline oxidase and Delta(1)-pyrroline-5-carboxylic acid (P5C) dehydrogenase. The level of induction by 20 mm baikiain is about 10% of the maximum level induced by proline. Since the analogue is a substrate of proline oxidase the first enzyme of the proline catabolic pathway, the oxidation derivative rather than baikiain itself might be the actual effector. Baikiain is also an inducer of proline oxidase in Escherichia coli K-12 and E. coli W. An additional effect of this analogue on proline degradation in S. typhimurium is inhibition of P5C dehydrogenase. At a concentration of 5 x 10(-4)m, baikiain inhibits completely the growth of strains constitutive for proline oxidase. This inhibition, which can be overcome by proline, occurs in the presence or absence of P5C dehydrogenase activity. Three spontaneously occurring mutants resistant to baikiain were isolated from constitutive strains. All are pleiotropic-negative for the proline-degrading enzymes. The sites of these mutations are linked to the put region. Although the mechanism of toxicity has not been determined, baikiain provides a simple and direct selection for obtaining mutants unable to degrade proline. In addition, it allows selection for strains with an inducible rather than constitutive phenotype.

Catalysis↗

PubMed1982

s-Cis...and s-trans isomerism in acylproline analogs. Models for conformationally locked proline peptides.

N-Acetyl-2,3-dehydroproline, N-acetyl-5-oxo-L-proline, N-acrylyl-L-proline, N-acetyl-L-azetidine-2-carboxylic acid and N-acetyl-D,L-pipecolic acid have been examined in 2H2O by 1H and 13Cn.m.r. for the purpose of finding s-cis or s-trans locked acylprolines. Conformationally locked acylprolines could be incorporated into proline-containing peptide hormones such as angiotensin and thyroliberin in order to determine the rotational state of the peptide bond to proline in the hormone receptor complex. The populations of trans and cis rotational isomers were determined as a function of p2H in order to assign the trans and cis isomers and to compare the populations in all the acylprolines at neutral p2H, where the cis isomer is normally present. Proton spectra were also recorded at from 7 degrees to 75 degrees in order to qualitatively determine the exchange rate between the isomers. The majority of these analogs exhibit a cis-trans isomerization similar to that of N-acetyl-L-proline in the ratio of trans to cis rotational isomer found at neutral p2H (about 1:1), the temperature dependence of the population ratio (none), and the coalescence temperature for proton resonances (greater than 75 degrees). However, N-acetyl-5-oxo-L-proline was found to be greater than 98% s-trans at neutral pH, compared to 50% s-trans in N-acetyl-L-proline, and therefore a good candidate for synthesis of an s-trans locked peptide hormone. N-Acetyl-2,3-dehydroproline rapidly exchanges between s-cis and s-trans in contrast to all other proline analogs examined and exhibits coalescence of the beta-proton cis and trans resonances at 45 degrees. Titration with the shift reagent Pr+++ was employed to confirm the assignments of the cis and trans methyl resonances of all of the N-acetyl compounds except N-acetyl-5-oxo-L-proline.

Magnetic Resonance Spectroscopy↗

PubMed1987

New approaches in peroxisomal disorders.

The peroxisome is a subcellular organelle with important functions in plants and protozoa, which during the last decade has also been shown to have a role in mammalian lipid and amino acid metabolism. These functions include steps in the synthesis of ether lipids and bile acids and fatty acid beta-oxidation, particularly those of very long chain fatty acids. The proposition that the peroxisome carries out significant functions in man is highlighted by the fact that lack of this organelle is associated with severe abnormalities in many human organs. Human peroxisomal disorders are now grouped into three general categories. In the first group, peroxisomes are lacking or reduced in number. This group includes the Zellweger cerebro-hepato-renal syndrome, neonatal adrenoleukodystrophy, infantile Refsum's disease and hyperpipecolic acidemia. These patients lack the capacity to synthesize ether lipids and to oxidize very long chain fatty acids or phytanic acid, and they show abnormally high levels of pipecolic acid and bile acid intermediates. These patients rarely survive early childhood, have severe neurological deficits and multiple malformations. A second group includes the 'pseudo-Zellweger' syndrome and the rhizomelic form of chondrodysplasia punctata. Here the peroxisomal structure is intact, but there is deficient function of several peroxisomal enzymes. The third group includes X-linked adrenoleukodystrophy, acatalasemia and 'adult' Refsum's disease. The peroxisomal structure is intact, and the defect in each instance is thought to involve a mutation which affects a single peroxisomal enzyme. Peroxisomal disorders are of current interest because they occur more commonly than had been recognized and show phenotypic and genotypic heterogeneity. Their study provides the opportunity to learn more about the role of the peroxisome in normal brain function and development.

Animals↗

PubMed1991

Antagonism of oxytocin in rats and pregnant rhesus monkeys by the novel cyclic hexapeptides, L-366,682 and L-366,948.

Two cyclic hexapeptides unrelated in chemical structure to oxytocin (OT) were shown in vivo to be antagonists of the contractile action of OT on the uterus. In anesthetized rats challenged with OT (1 micrograms/kg) administered as an i.v. bolus, L-366,682 [cyclo-(L-Pro-D-Trp-L-Ile-D-pipecolic acid-L-pipecolic acid-D-His)] and L-366,948 (D-2-naphthyl-alanine in place of D-Trp) were equipotent with AD50 values of about 100 micrograms/kg i.v. At doses of L-366,682 or L-366,948 causing approximately 90 to 95% block (approximately the AD95 dose) of OT, the duration of action of the antagonists exceeded 145 min. Both compounds exhibited selectivity in the rat, as a dose of either at 300 micrograms/kg i.v. shifted the dose-response for OT-induced uterine contraction to the right by approximately 5-fold but did not affect the dose-response to prostaglandin F2 alpha. Furthermore, neither compound, at a dose of 3 mg/kg i.v., antagonized the action of arginine vasopressin acting at V-1 (pressor effect in pithed rats) or V-2 (antidiuretic) receptors. In conscious, freely moving, pregnant rhesus monkeys, L-366,948 or L-366,682 given i.v. or s.c. were effective antagonists of uterine contractions elicited by an infusion of OT. OT- or arginine vasopressin-like agonist activity was not observed in any of the in vivo models. It is concluded that L-366,682 and L-366,948 act in vivo as reasonably potent, long-acting and selective antagonists at OT receptors in the rat and rhesus uterus.

Animals↗

PubMed1996

SK&F 105494, a V2-vasopressin receptor antagonist, blocks oxytocin receptors in porcine myometrium.

AIM: To study the effects of SK & F 105494 (SK & F), a V2-vasopressin receptor antagonist, on lypressin (Lyp)- and oxytocin (Oxy)-induced increases in myometrial contractility. METHODS: Uterine strips isolated from sows in the luteal phase of the estrous cycle were used to study the contractility. The receptor binding assays were performed to study the Oxy receptor blocking activity. RESULTS: Lyp and Oxy caused a concentration-dependent increase in myometrial contractility with EC50 of 50 +/- 14 nmol.L-1 and 170 +/- 32 pmol.L-1, respectively. SK & F 30-300 nmol.L-1 antagonized the contractile effects of Lyp and Oxy in a concentration-dependent manner. When the concentration-dependent inhibition of [3H] Oxy binding by SK & F was compared with Lyp and L-366948 [(cyclo-(L-Pro-D-2-naphthyl-Ala-L-lle-D-pipecolic acid-L-pipecolic acid-D-His)], a potent antagonist specific for Oxy receptors, the Ki values for SK & F, Lyp, and L-366948 were 1.73 +/- 0.32, 14.36 +/- 1.73, and 1.79 +/- 0.35 nmol.L-1, respectively. CONCLUSION: SK & F has a potent Oxy receptor blocking activity in addition to its known V2-receptor blocking activity.

Animals↗

PubMed1995

Distinction between peroxisomal bifunctional enzyme and acyl-CoA oxidase deficiencies.

The clinical distinction between patients with a disorder of peroxisome assembly (e.g., Zellweger syndrome) and those with a defect in a peroxisomal fatty acid beta-oxidation enzyme can be difficult. We studied 29 patients suspected of belonging to the latter group. Using complementation analysis, 24 were found to be deficient in enoylcoenzyme A hydratase/3-hydroxyacylcoenzyme A dehydrogenase bifunctional enzyme and 5 were deficient in acyl-CoA oxidase. Elevated plasma very long-chain fatty acids (VLCFA), impaired fibroblast VLCFA beta-oxidation, decreased fibroblast phytanic acid oxidation, normal plasmalogen synthesis, normal plasma L-pipecolic acid level, and normal subcellular catalase distribution were characteristic findings in both disorders. The elevation in plasma VLCFA levels and impairment in fibroblast VLCFA beta-oxidation were more severe in bifunctional-deficient than in oxidase-deficient patients. The clinical course in bifunctional deficiency (profound hypotonia, neonatal seizures, dysmorphic features, age at death approximately 9 months) was more severe than in oxidase deficiency (moderate hypotonia without dysmorphic features, development of a leukodystrophy, age at death approximately 4 yr). Based on these findings, accurate early diagnosis of these deficiencies of peroxisomal beta-oxidation enzymes is possible.

Acyl-CoA Oxidase↗

PubMed1992

Efficient enantioselective separation and determination of trace impurities in secondary amino acids (i.e., imino acids).

An R-(-)-1-(1-naphthyl)ethyl carbamoylated-beta-cyclodextrin bonded phase in conjunction with a nonaqueous polar mobile phase was used for the highly selective enantioseparation of a number of secondary amino acids after their pre-column derivatization with 9-fluorenylmethyl chloroformate (FMOC). Under the conditions employed, the FMOC reagent served to "lock" the imino acid into their existing conformation thereby preventing the possibility of racemization. Furthermore, it served to increase the sensitivity to the point that trace level enantiomeric impurities were easily detected. Compared with separations that use traditional reversed-phase solvents, this method showed several advantages: higher selectivity towards the imino acid enantiomers investigated, shorter analysis times, faster equilibration of the column, more stable baseline and more sensitive fluorescence detection. The detection limits for FMOC derivatives of proline, trans-4-hydroxyproline, cis-4-hydroxyproline, pyroglutamic acid, 3,4-dehydroproline, thiaproline, penicillamine acetone adduct and pipecolic acid are in the low femtomole range. The method was used for evaluation of enantioselectivity of a number of "optically pure" commercial imino acid standards. Enantiomeric impurities as low as 0.0001% (1 ppm) can be determined in some cases. High precision determination of trace levels of D-imino acids in the presence of large amounts of corresponding (opposite) L enantiomer at 1, 0.1, 0.01% and below are demonstrated.

Amino Acids↗

PubMed2002

The proton affinity of proline analogs using the kinetic method with full entropy analysis.

The proton affinity of proline analogs, L-azetidine-2-carboxylic acid (Aze), L-proline (Pro), and L-pipecolic acid (Pip), have been measured using the Armentrout modification of the extended kinetic method in a quadrupole ion trap instrument. Experimental values of 223.0 +/- 1.5, 224.9 +/- 1.6, and 225.6 +/- 1.6 kcal/mol have been determined for the 298K proton affinities of Aze, Pro, and Pip respectively. High level theoretical calculations using both MP2 and B3LYP methods at a variety of basis sets were carried out in order to give theoretical predictions for the 298 K proton affinity and gas phase basicity of all three analogs. Recommended values for the gas phase basicity and proton affinity for proline based on our work and other recent determinations are 216 +/- 2 and 224 +/- 2 kcal/mol.

Computational Biology↗

PubMed1976

Lysine Catabolism in Barley (Hordeum vulgare L.).

Lysine catabolism in seedlings of barley (Hordeum vulgare L. var. Emir) was studied by direct injection of the following tracers into the endosperm of the seedlings: aspartic acid-3-(14)C, 2-aminoadipic acid-1-(14)C, saccharopine-(14)C, 2,6-diaminopimelic acid-1-(7)-(14)C, and lysine-1-(14)C. Labeled saccharopine was formed only after the administration of either labeled 2,6-diaminopimelic acid or labeled lysine to the seedlings. The metabolic fate of the other tracers administered also supported a catabolic lysine pathway via saccharopine, and apparently proceeding by a reversal of some of the biosynthetic steps of the 2-aminoadipic acid pathway known from lysine biosynthesis in most fungi. Pipecolic acid seems not to be on the main pathway of l-lysine catabolism in barley seedlings.

Journal Article↗

PubMed1995

The role of peroxisomes in intermediary metabolism.

The dominant position among oxidoreduction processes in peroxisomes is ascribed to catalase, a number of aerobic oxidases, and Cu,Zn-superoxide dismutase. The peroxidase reaction of catalase requires substrates for hydrogen donation, other than H2O2, e.g. alcohols, aldehydes, formic acid. The peroxisomes contain an alternative system of beta-oxidation of higher carboxylic acids which in some types of plant cells is functionally very closely associated with the glyoxylate cycle. Regarding the role of peroxisomes in the metabolism of carboxylic acids, a very important finding has taken place, namely that besides acyl-CoA synthetase which is specific for long chains, the peroxisomes contain still another enzyme which allows the synthesis of CoA esters of fatty acids with very long chains. It is assumed that the entry of acyl-CoA esters or fatty acids into the perxisomes is performed by means of pores in membranes or acyl-carnitine transferases. Peroxisomes oxidize a very wide scale of substrates and contain several types of acyl-CoA oxidases: palmitoyl-CoA oxidase, pristanoyl-CoA oxidase, trihydroxy-coprostanoyl-CoA oxidase. The second and third reactions of peroxisomal beta-oxidation are catalyzed by the so-called three-functional enzyme, the activities of which are identical to those of 2-enoyl-CoA hydratase, beta-hydroxyacyl-CoA dihydrogenase and enoyl-CoA isomerase. The peroxisomes sufficiently oxidize dicarboxylic acids with a higher number of carbons beginning with the adipic acid. The peroxisomal system of beta-oxidation is utilized in metabolism of prostaglandins, pristanic acid-being the product of phytanic acid alpha-oxidation, and cholesterol. Several enzymatic activities needed for the synthesis of cholesterol partially take place in peroxisomes. The peroxisomes represent a decisive compartment for the initial phases of synthesis of plasmalogens. They contain the following enzymes: NAD(+)-glycerol-P-dehydrogenase, dihydroxyacetone-3-P-acyl-transferase, alkyl-dihydroxyacetone-P synthetase and acyl/alkyl-dihydroxyacetone-P reductase. The metabolism of amino acids takes place under the effect of peroxisomal enzymes--oxidase of diamino acids, D-aspartate oxidase, oxidase of L-pipecolic acid and alanine-glyoxylate aminotransferase. Only a few published sources consider it obvious that liver peroxisomes participate in degradation of spermine and spermidine. Polyamine oxidase oxidizes spermine resulting in the origin of spermidine and 3-aminopropionaldehyde, and spermidine is oxidized to putrescine and 3-aminopropionaldehyde. Peroxisomes in many phylogenetically lower animal species enable the break down of purine bases to urea and glyoxylic acid. In phylogenetically higher primates and in man, the activities of urate oxidase in peroxisomes are absent. (Fig. 14, Ref. 166).

Amino Acids↗

PubMed1993

Complementation analysis of patients with intact peroxisomes and impaired peroxisomal beta-oxidation.

Complementation analysis, using peroxisomal beta-oxidation of very long chain fatty acids (VLCFA) as the criterion for complementation, is useful in the study of patients who are suspected of having a single enzyme defect in the peroxisomal beta-oxidation pathway. Laboratory findings for these patients include elevated plasma VLCFA and impaired VLCFA oxidation in fibroblasts. Some of these patients have slightly abnormal phytanic acid oxidation in fibroblasts. In addition, elevated levels of bile acid intermediates have been reported in some cases. Plasmalogen synthesis, pipecolic acid levels, and subcellular distribution of catalase are normal. Using complementation analysis, we show that six patients, who were suspected of having a single enzyme defect in the peroxisomal beta-oxidation pathway, are deficient in peroxisomal bifunctional enzyme [enoyl-CoA hydratase (EC 4.2.1.17)/3-hydroxyacyl-CoA dehydrogenase (EC 1.1.1.35)] activity. This group of six patients, deficient in bifunctional enzyme activity, may be subdivided into two complementation groups. It would appear that patients in each of these two groups are deficient in only one of the bifunctional enzyme activities.

3-Hydroxyacyl CoA Dehydrogenases↗

PubMed1997

[Peroxisomal hereditary diseases].

Nearly two tens of diseases are known to be caused by impairment of several metabolic functions of peroxisomes, or by deficiency in individual peroxisomal enzymes. With the exception of X-bound adrenoleukodystrophy, all diseases are based on autosomally recessive type of inheritance and a majority of them are characteristic by specific neurologic symptoms. The group of diseases in which patients develop a generalised loss of peroxisomal functions includes: Zellweger's cerebro-hepato-renal syndrome, neonatal adrenoleukodystrophy, infantile Refsum's disease, hyperpipecolic acidaemia. Other diseases, such as rhizomelic chondrodysplasia punctata and Zellweger-like syndrome are accompanied by a deficiency in several enzymatic activities. X-bound adrenoleukodystrophy, pseudo-Zellweger's syndrome, hyperoxaluria 1, adult form of Refsum's disease and acatalasaemia are peroxisomal diseases with a deficiency of a single enzyme. In clinically most severe diseases (generalised loss of peroxisomal functions), the impairment of peroxisomal biogenesis is caused assumedly due to the defect in some of the peroxisomal membrane proteins. The biochemical findings are brought about by insufficiency in such metabolic functions as oxidation of fatty acids with very long chains, oxidation of the phytanic and pipecolic acids, synthesis of cholesterol, bile salts and plasmalogenes. Rhizomelic chondrodysplasia punctata and Zellweger's syndrome are more moderate forms which are dominantly biochemically manifestant by an impairment in the synthesis of plasmalogenes. Among the diseases characterised by a deficiency in individual peroxisomal enzymes, most frequent is the X-bound andrenoleukodystrophy which has several clinical phenotypes manifestant in childhood, as well as a clinically less severe form manifestant in adulthood-adrenomyeloneuropathy. The diagnosis of peroxisomal diseases is performed by use of a wide range of methods (morphological, biochemical, immunochemical and molecular genetic examinations) which enable both postnatal and prenatal diagnostics. (Tab. 1, Ref. 104.)

Humans↗

PubMed1986

Structural features facilitating the glutamate dehydrogenase catalyzed alpha-imino acid-alpha-amino acid interconversion.

Glutamate dehydrogenase catalyzes the reversible oxidation of L-proline and L-pipecolic acid to the corresponding cyclic alpha-imino acids. The active substrates are the amino acid anion in one direction and the iminium ion in the other. The oxidation of the ester, amide, and N-methyl derivatives of L-proline by enzyme-NADP+ and the reduction of N-methyl-delta 1-tetrahydropyridinium ion by enzyme-NADPH do not proceed to a detectable extent under the experimental conditions. The methyliminium ion, however, undergoes facile nonenzymatic reduction by NADPH. If it is assumed that the nonenzymatic reaction reflects the structural requirements of the redox step of the enzymatic reaction, then the lack of reactivity of the tetrahydropyridinium ion toward enzyme-NADPH must be due to the instability of the central complex. It appears that the alpha-carboxylate and NH groups in the amino acid anion and in the alpha-imino acid are involved in binding the substrates to the enzyme-coenzyme complexes. We conclude that each of these active substrates binds to its appropriate enzyme-coenzyme complex through a hydrogen bond between its NH group and a basic enzyme group; there is also an ionic bond in the central complex between the alpha-carboxylate group of the active substrate and a positively charged enzyme group. The five-membered amino acid anions are more reactive toward enzyme-NADP+ than the six-membered ones. The same reactivity order is seen for the reduction of imino acids by enzyme-NADPH. Since these effects are also present in the nonenzymatic reduction by NADPH we ascribe the ring size effects on V/Ksubstrate primarily to those on the hydride-transfer step.

Amino Acids↗

PubMed1992

Complementation in Zellweger syndrome: biochemical analysis of newly generated peroxisomes.

The Zellweger syndrome is characterized by a defect which results in the abnormal biogenesis of peroxisomes. As a consequence, metabolic activities associated with peroxisomes such as the oxidation of very long chain fatty acids, the synthesis of plasmalogens, and the catabolism of phytanic and pipecolic acids are impaired. Since this disorder is genetically heterogeneous and several complementation groups are known, we were able to study the normalization of peroxisomal activity during the process of complementation. The restoration of catalase and dihydroxyacetone phosphate acyltransferase activities peaked within 3-4 days postfusion while the oxidation of lignoceric acid was much delayed (7-8 days). Electron microscopy indicated that by 6 days following hybridization, peroxisome structure and density in heterokaryons was comparable to normal control cells. The heterogenous biochemical response during peroxisome normalization could be due to several factors including a possible requirement for restoration of peroxisomal structural integrity for maximum activation of certain metabolic pathways.

Acyltransferases↗