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Biomedical subjects

F A Hommes

Publications and source records attributed to F A Hommes.

At least 55 records · Page 3Linked to original sources
PubMed1984

The uptake of ornithine and lysine by isolated hepatocytes and fibroblasts.

The uptake of ornithine and lysine by isolated hepatocytes and cultured human skin fibroblasts were studied. Both types of cells can accumulate these amino acids via a saturable and a non-saturable process, the latter being active at high substrate concentration. The apparent Km for ornithine and lysine for the saturable process in hepatocytes were 0.26 and 0.94 mM respectively, those values for fibroblasts were found to be 0.43 and 0.57 mM respectively. Fractionation of the cells by the digitonin technique into a cytosolic compartment and a particulate compartment, showed that a rapid equilibration occurs between the external medium and the cytosolic compartment of hepatocytes and fibroblasts.

Animals↗
PubMed1984

Further evidence for a separate enzymic entity for the synthesis of homocitrulline, distinct from the regular ornithine transcarbamylase.

Differential digitonin extraction of rat liver mitochondria and of mitochondria of livers of affected and unaffected male sparse fur mice released a lysine transcarbamylase activity from the mitochondria at a digitonin to protein ratio in between that for myokinase and glutamate dehydrogenase, but at a slightly lower ratio than the ornithine transcarbamylase activity. Homocitrulline formation by isolated rat liver mitochondria is independent of the uptake of lysine by mitochondria as evidenced by the insensitivity of homocitrulline formation to changes in the matrix pH, in contrast to citrulline formation from ornithine. High-performance liquid chromatography separates the lysine transcarbamylase activity from the ornithine transcarbamylase activity. It is concluded that the lysine transcarbamylase activity is localized outside the inner mitochondrial membrane.

Animals↗
PubMed1983

The uptake of ornithine and lysine by rat liver mitochondria.

Ornithine and lysine are taken up by rat liver mitochondria with an apparent Km of 1.3 and 2.4 mM, respectively. Neither lysine methylester alpha-N-acetyl lysine, nor epsilon-N-acetyl lysine inhibits the uptake of either ornithine or lysine. The zwitterionic form of these amino acids is taken up by liver mitochondria. Lysine inhibits the uptake of ornithine and vice versa. The inhibition is in both cases of the mixed type. Arginine strongly inhibits the uptake of both ornithine and lysine. Alkalinization of the mitochondrial matrix decreases the rate of uptake of ornithine and of lysine, while acidification of the mitochondrial matrix increases these rates. It is concluded that ornithine and lysine are taken up via a common carrier in exchange for H+.

Animals↗
PubMed1983

Effect of experimental hyperphenylalaninemia on biogenic amine synthesis at later stages of brain development.

The effects of experimental hyperphenylalaninemia on catecholamine and serotonin synthesis in brain at a later stage of brain development were investigated. A group of 35-day-old rats treated with normal chow supplemented with 5% Phe + 0.4% alpha-methylphenylalanine, alpha MP, for the previous 10 days showed decreases in dopa, norepinephrine, and epinephrine versus controls. A group treated with a normal diet supplemented with 0.4% alpha MP showed similar decreases and these differences could be attributed to the presence of the phenylalanine hydroxylase and tyrosine hydroxylase inhibitor, alpha MP, rather than the hyperphenylalaninemia condition. No differences in dopamine were observed. Serotonin and 5-hydroxyindoleacetic acid (5HIAA) were decreased 50% in the HyPhe condition and were unaffected in the presence of alpha MP alone, indicating that the decreases in serotonin and 5HIAA were due to the increases in phenylalanine rather than the presence of the inhibitor. These abnormalities in serotonin metabolism at later stages of brain development may be relevant to early discontinuation of dietary therapy in the PKU patient and implies a role in tryptophan supplementation to increase intracerebral serotonin values.

Animals↗
PubMed1983

Separation of ornithine and lysine activities of the ornithine-transcarbamylase-catalyzed reaction.

Several lines of evidence are presented that an entity is present in mitochondria which converts lysine and carbamylphosphate to homocitrulline, distinct from the ornithine transcarbamylase (OTC): lack of inhibition by lysine of OTC with ornithine as substrate at the pH of the mitochondrial matrix, a Km for lysine of 6.3 mmol/l in the crude mitochondrial extract, versus a Km of 55.3 mmol/l after partial purification of OTC, decrease of the specific activity of OTC with lysine as substrate and increase of the specific activity with ornithine as substrate after heat denaturation, and separation of the activities for ornithine and lysine after isoelectric focusing. This would explain the excretion of homocritrulline in the HHH-syndrome, saccharopinuria, citrullinemia and hyperlysinemia. The fact that homocitrulline excretion is not observed in OTC deficiency suggests that the activity responsible for homocitrulline excretion is closely related to OTC.

Animals↗
PubMed1983

Effect of experimental hyperphenylalaninemia on myelin metabolism at later stages of brain development.

Myelination is the most important process in postnatal maturation of the nervous system and during this period the growing infant passes through a "vulnerable period" during which irreversible brain damage can occur if the neonate is subjected to a potential neurotoxin. This study was undertaken to investigate the mechanisms by which chronic hyperphenylalaninemia interferes with myelin metabolism, beyond the neonatal period of rapid myelination, at a time when myelin continues to accumulate. Rats of 25 days of age were placed on a hyperphenylalanimenia (HyPhe) inducing diet of 5% phenylalanine plus 0.4% alpha-methylphenylalanine (alpha MP) at 25 days of age to approximate plasma phenylalanine levels of an untreated human PKU patient (1.5 mM). The HyPhe group exhibited approximately a 15% decrease in the amount of myelin protein throughout the 70 days of the study. The rate of incorporation of 3H-lysine into both TCA precipitable whole brain proteins or myelin proteins did not vary from the HyPhe group and a weight matched control group (WMC). Therefore, this loss of myelin could not be attributed to a hypo-myelination. The turnover of whole brain proteins also was unaffected by the HyPhe treatment; however, the turnover of myelin proteins in the HyPhe group was dramatically different (t 1/2 = 3 days) from that of the WMC group (t 1/2 = 36 days) or a group treated with only alpha MP (t 1/2 = 26 days).

Amino Acids↗
PubMed1982

Turnover of the fast components of myelin and myelin proteins in experimental hyperphenylalaninaemia. Relevance to termination of dietary treatment in human phenylketonuria.

The turnover of myelin and of myelin protein fractions has been measured in the central nervous system of rats who were placed on a hyperphenylalaninaemia-inducing diet (3% L-phenylalanine and 0.12% p-chlorophenylalanine added to the normal laboratory chow) when they were 25 days of age. A considerably increased turnover of the fast component of myelin and of myelin protein fractions was observed, which was not found in weight-matched controls or in controls fed the normal laboratory chow supplemented with 0.12% p-chlorophenylalanine. The increased turnover is therefore due to the hyperphenylalaninaemic condition and not due to the slow-down in growth or the presence of p-chlorophenylalanine. Furthermore, an inhibition of myelin synthesis due to the hyperphenylalaninaemic condition has been observed. Since these effects on myelin metabolism can be demonstrated to occur even when the brain has matured considerably, prudence should be exercised in considering the termination of the dietary treatment of patients with phenylketonuria.

Amino Acid Metabolism, Inborn Errors↗
PubMed1982

Decreased transport of ornithine across the inner mitochondrial membrane as a cause of hyperornithinaemia.

Hyperornithinaemia due to a transport of ornithine across the inner mitochondrial membrane was demonstrated in three patients by measuring ornithine uptake by fibroblast mitochondria. Particulate compartments and soluble cytoplasm of fibroblasts were separated by a slight modification of the digitonin method of Zuurendonk and Tager. Patients' fibroblast pellet fraction contained significantly less radioactivity than control fibroblast pellet fraction after incubation of fibroblasts with [14C]-ornithine. Since neither of the patients was deficient in ornithine-delta-oxoacid aminotransferase, we concluded that in these hyperornithinaemia patients a defect exists for transport of ornithine across the inner mitochondrial membrane. The exact nature of this transport defect remains to be elucidated.

Amino Acid Metabolism, Inborn Errors↗
PubMed1982

Cell genetic studies on propionyl-CoA carboxylase deficient cell lines.

Thirteen propionyl-CoA carboxylase (PCC)-deficient fibroblast lines were analysed for complementation by examining the incorporation of [14C]propionate into trichloroacetic-acid insoluble cellular macromolecules of polyethylene-glycol-dimethyl-sulphoxide induced heterokaryons formed by fusion of mutant cell lines. Corrections for variations in the rate of protein synthesis of the heterokaryons and individual cell lines was made by measuring the incorporation of [3H]lysine, added simultaneously with the labelled propionate. Two distinct complementation groups were found in this sample of PCC-deficient cell lines. Evidence for intragenic complementation was not obtained.

Carboxy-Lyases↗
PubMed1982

Plasma phenylalanine and tyrosine levels during the day in normal female controls and female obligate phenylketonuria heterozygotes.

The plasma phenylalanine and tyrosine levels of 8 female obligate phenylketonuria heterozygotes and 8 female controls have been measured over a 7-hour period during the day. No significant differences were observed in the plasma tyrosine levels. It is concluded that the supply of tyrosine to the growing fetal brain is not necessarily impaired by the decreased ability to convert phenylalanine to tyrosine of the phenylketonuria heterozygous mother.

Female↗
PubMed1981

A patient with pyruvate carboxylase deficiency in the liver: treatment with aspartic acid and thiamine.

A seven-year-old girl with slowly progressive motor neurological impairment and high levels of lactate and pyruvate in blood and cerebrospinal fluid was found to have severe hepatic pyruvate carboxylase deficiency. However, in contrast to other patients with this deficiency, no mental retardation was apparent. Treatment with aspartic acid and thiamine over a period of seven years resulted in biochemical improvement and a stable neurological condition. The level of cognitive functioning remained the same. When treatment with aspartic acid was temporarily discontinued, lactate and pyruvate concentrations increased so markedly that the drug was resumed. This indicates that aspartic acid was the effective drug, and that the effect of thiamine was secondary.

Aspartic Acid↗
PubMed1980

The energy requirement for growth. A reevaluation.

The energy requirement for synthetic processes during growth in the male reference baby of 3,900 g at 3 weeks of age, growing along the 50th percentile have been recalculated, taking into account physiological values for P/O ratios of NAD- and FAD-linked substrates in oxidative phosphorylation and the processing and splicing of precursor RNA. An amount of 2.1% of the total energy intake is needed to cover the needs for synthetic processes associated with growth.

Energy Intake↗
PubMed1980

[Chronic infantile lactate acidosis].

A baby with congenital lactic acidosis is described. The blood levels of lactic acid and alanine as well as the excretion of these compounds in the urine were largely elevated. Clinically the illness presented with vomiting, poor feeding, areflexia, muscular hypotonia and hepatomegaly. The baby died at the age of three months. The pyruvate dehydrogenase complex in cultured fibroblasts showed an activity of 14% of normal values.

Acidosis↗