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L M Henderson

Publications and source records attributed to L M Henderson.

At least 91 records · Page 5Linked to original sources

Transport and metabolism of carnitine precursors in various organs of the rat.

Isolated, vascularly perfused small intestine, liver, and kidney were used to investigate their interdependence in the absorption and metabolism of carnitine precursors in the rat. During 30 min of recirculating perfusion, the small intestine absorbed trimethyllysine, hydroxytrimethyllysine, and trimethylaminobutyrate fairly well when they were administered via the lumen or the perfusate. Trimethylaminobutyrate was synthesized from either trimethyllysine or hydroxytrimethyllysine by the small intestine, but further hydroxylation of trimethylaminobutyrate to carnitine did not occur. Trimethyllysine and hydroxytrimethyllysine were not readily absorbed by the liver. In contrast, trimethylaminobutyrate and trimethylaminobutyraldehyde were rapidly absorbed from the perfusate and readily incorporated into carnitine by the liver. Trimethyllysine and hydroxytrimethyllysine were taken up slowly by the kiodney and partially converted to trimethylaminobutyrate during 3409 min of perfusion. Trimethylaminobutyrate was neither absorbed readily by the kidney nor was it hydroxylated to carnitine. These results were compared to whole animal studies performed over an equivalent time period. The data suggest that the isolted small intestine absorbs trimethyllysine well, but it probably plays a minor role in metabolizing physiological quantities of this compound in the whole animal where other organs are competing for the same substrate. In both the isolated organ and in the whole animal, the kidney absorbs and metabolizes trimethyllysine more readily than the liver; whereas the liver absorbs trimethylaminobutyrate more rapidly than either the kidney or the small intestine and, unlike these organs, converts it to carnitine.

Absorption↗

Carnitine biosynthesis. Purification of 4-N'-trimethylaminobutyraldehyde dehydrogenase from beef liver.

4-N-Trimethylaminobutyrate is formed during carnitine biosynthesis by the oxidation of 4-N-trimethylaminobutyraldehyde. The aldehyde dehydrogenase which catalyzes this reaction has been isolated from bovine liver. This enzyme was purified to homogeneity, as judged by sodium dodecyl sulfate polyacrylamide gel electrophoresis, using two affinity type columns. Blue dextran and 5'-AMP covalently linked to a Sepharose matrix were used to bind this NAD+-requiring enzyme. Two other aldehyde dehydrogenases with broader specificities were also purified to homogeneity using the same affinity columns. The three enzymes appear to be distinct as they are different with respect to subcellular locations, substrate specificity, behavior on the affinity columns, disulfiram inhibition, and esterase activity. The enzyme with preference for trimethylaminobutyraldehyde as substrate probably functions in carnitine biosynthesis.

Aldehyde Oxidoreductases↗

Transport and metabolism of pyridoxine in the perfused small intestine and the hind limb of the rat.

The vascularly perfused small intestine and hind limb muscle of the rat were utilized to study the transport and metabolism of pyridoxine (PN), independent of other tissues, including erythrocytes. The transport of PN both into the mucosal tissue and transmurally into the perfusate was proportional to the dose over a 10,000-fold range of concentrations. The only labeled compound formed from [3H]-PN in the mucosa was PNP which accounted for 30.6% of the isotope found there. The data for the hind limb muscle suggest that transport occurs by passive diffusion followed by phosphorylative trapping. Over a 10,000-fold range of concentrations of PN in the perfusate, the percentage of 3H found in the muscle ranged from 10.4 to 15.7 for 30-minute experiments. As the dosage was increased the percentage of 3H in the muscle, present as PN increased and that in PNP decreased. In longer experiments, up to 75 minutes, with 20 nmole of [3H]-Pn, the PN in muscle decreased as phosphorylation occurred. There was no evidence of any conversion of PNP to PLP (pyridoxal phosphate) in the perfused hind limb.

Animals↗

Inheritance of Ag-stainability of the nucleolus organizer regions in domestic sheep, Ovis aries.

One of the nucleolus organizer regions of sheep is located on chromosome 25, which forms one arm of a Robertsonian translocation chromosome (t3). By mating sheep heterozygous and homozygous for the t3 chromosome, and with various Ag-staining frequencies and deposit sizes, the heritability of the Ag-stainability could be determined. The inheritance of Ag-stainability was studied in 54 sheep in five pedigree groups. It was shown that the Ag-staining of a NOR is a heritable property. Matings of animals heterozygous for Ag-stainability provided an estimate of recombination frequency of the short arm of t3.

Animals↗

Metabolism of niacin and niacinamide in perfused rat intestine.

The metabolism of [14C]nicotinic acid and [14C]nicotinamide by perfused rat intestine was studied by analyzing the 14C-products formed at various time intervals after these substrates were administered intravascularly or intralumenally. Intermediates in the Preiss-Handler pathway contained isotope when [14C]nicotinic acid was administered by either route. Large amounts of isotope in niacinamide and some in nicotinamide mononucleotide (NMN) were also found indicating substantial NAD-glycohydrolase activity in this intestinal preparation. The products from [14C]nicotinamide also included the metabolites of nicotinic acid, due to deamidation of the substrate in the lumen when the exposure was prolonged. In short term studies the amide was absorbed rapidly by simple diffusion with little hydrolysis to nicotinic acid. The primary labeled form found in the perfusate when [14C]nicotinic acid was administered via the lumen for both recirculating and one pass perfusions was unchanged nicotinic acid. The primary forms found in the perfusate when the amide was given were both the amide and the acid for both one pass and for recirculating experiments. The rapid transport of nicotinamide from the lumen to the perfusate and the lack of 14C-metabolites of nicotinic acid in the intestinal tissue following intralumenal injection of [14C]nicotinamide in the living animal suggest that deamidation in the digestive tract is not a major fate of physiological quantities of niacinamide.

Animals↗

Transport and metabolism of pyridoxamine and pyridoxamine phosphate in the small intestine of the rat.

The vascularly perfused small intestine of the rat was utilized to study the absorption and metabolism of pyridoxamine (PM) and pyridoxamine-5'-phosphate (PMP), independent of other tissues including erythrocytes. [3H]PM or [3H]PMP was administered intralumenally with or without the addition of unlabeled PM, or PMP or inorganic phosphate. The percentage absorption of PM was 17.1 to 19.7% in 10 minutes and was unaffected by dosages from 0.02 to 200 mumole. The isotope from [3H]PMP at a physiological level (0.02 mumole) was absorbed at the same rate as that from [3H]PM, and the distribution of the 3H remaining in the lumen and in the intestinal tissue and perfusate indicated that hydrolytic removal of the phosphate was occurring extensively in the gut. The spectrum of labeled compounds isolated from the lumen, the perfusate and the mucosa clearly indicated that PMP, unhydrolyzed, can be absorbed slowly and converted to a number of vitamin B-6 forms in the intestinal mucosa. However, the results support the view that under normal physiological conditions the majority of dietary PMP is hydrolyzed to PM which seems to be absorbed by passive diffusion and transported to other organs and tissues via the blood stream.

Animals↗

Conservation of nucleolus organizer regions during evolution in sheep, goat, cattle and aoudad.

There are ten nucleolus organizer regions (NORs) in domestic sheep (Ovis aries L.). cattle (Bos taurus L.), goat (Capra hircus L.) and aoudad (Ammotragus lervia Blyth) and these are located terminally on chromosomes with homologous (G-banding patterns. The similarity in number of nucleolus organizer regions in these species may indicate that their ribosomal DNA regions are infrequently involved in exchange events which could lead to different numbers of active nucleolus organizer regions. Other possible explanations of the conservation of number of nucleolus organizer regions in these species are discussed. The homology of NOR location in these species supports the idea that the Bovidae karyotype tends to be fairly stable apart from changes due to centric fusion events.

Animals↗

Carnitine biosynthesis. beta-Hydroxylation of trimethyllysine by an alpha-ketoglutarate-dependent mitochondrial dioxygenase.

Rat liver mitochondria were found to hydroxylate epsilon-N-trimethyl-L-lysine to produce beta-hydroxy-epsilon-N-trimethyl-L-lysine, an intermediate in carnitine biosynthesis. The hydroxylating system requires alpha-ketoglutarate, Fe2+, and ascorbate, but does not require NADPH nor NADH. No activity was found in the microsomal or soluble fractions of liver extracts. The hydroxylated alpha-amino acid was isolated and characterized by column chromatography using Dowex 50-H+ and Chelex 100-Cu2+ resins and by high voltage paper electrophoresis. The enzymatically produced beta-hydroxy-epsilon-N-trimethyl-L-lysine was shown to be periodate-sensitive and one periodation product was characterized as gamma-butyrobetaine aldehyde. The hydroxylated product was acted upon by crystalline serine transhydroxymethylase (EC 2.1.2.1) to yield gamma-butyrobetaine aldehyde and glycine. Conversion of about 40% of the epsilon-N-trimethyl-L-lysine to beta-hydroxy-epsilon-N-trimethyl-L-lysine was accomplished by this system with little or no further metabolism.

Animals↗

Association of nucleolus organizer chromosomes in domestic sheep (Ovis aries) shown by silver staining.

The nucleolus organizer regions of domestic sheep (Ovis aries), as shown by silver staining, are located terminally on chromosomes 1, 2, 3, 4, and 25. Significant differences between individuals in the number of Ag-NORs per cell were found. The frequency of involvement of individual chromosome pairs in nucleolar organization was found to be a characteristic of individual animals. Association frequencies of individual chromosomes were accounted for by their frequency of participation in nucleolar organization. No evidence for nonrandom association of chromosome pairs was found.

Animals↗

Metabolism of D- and L-tryptophan in dogs.

The metabolism of D- and L-[benzene ring-U-14C]tryptophan by dogs was studied. The distribution of label from each isomer in urine, feces, CO2 and various tissues was determined. Thirteen different urinary tryptophan metabolites were isolated by ion exchange cellulose chromatography. D-[14C]Tryptophan was poorly converted to 14CO2 relative to the L-isomer, while giving rise to nearly three times as much urinary 14C as did the L-isomer. The major urinary metabolites of D-tryptophan were unchanged D-tryptophan via indolepyruvic acid appeared to be the major fate of ingested D-tryptophan, with renal excretion of the unchanged D-isomer the next most important fate. The dog apparently utilizes D-tryptophan more efficiently than does the human but much less efficiently than does the rat. The dog appears to be a reasonable animal model for the human in studies of D-tryptophan metabolism.

Animals↗

Metabolism of 5-hydroxylysine in Pseudomonas fluorescens.

Hydroxylysine is metabolized via two routes by a Pseudomonas fluorescens strain as shown by the oxidation of selected intermediates. Hydroxy-L-lysine is oxidized via a pathway analogous to the monooxygenase pathway for L-lysine, and data suggest that at least some of tthe enzymes are those involved in the metabolism of L-lysine. Hydroxy-L-lysine is also converted by a racemase to allohydroxy-D-lysine, which is then degraded via a pathway analogous to, but different from, that described for D-lysine, involving hydroxy-L-pipecolate, 2-amino-5-hydroxyadipate, and 2-hydroxyglutarate. Data obtained with mutants unable to oxidize L-pipecolate suggest that the enzymes for the metabolism of hydroxy-L-pipecolate are distinct from those for L-pipecolate. Studies on D- and L-lysine degradation have shown that the previously described pathways for these compounds are present in this soil pseudomonad.

2-Aminoadipic Acid↗

Cerebral arterial spasm. Part 4: in vitro effects of temperature, serotonin analogues, large nonphysiological concentrations of serotonin, and extracellular calcium and magnesium on serotonin-induced contractions of the canine basilar artery.

In vitro experiments were performed using a small volume chamber to study serotonin-induced contractions of the canine basilar artery. Temperature was found to have a profound effect on the artery's response to serotonin. Raising the temperature to 40 degrees C (104 degrees F) increased the maximum response by 20% and lowering the temperature by 10 degrees C caused a 40% reduction in the maximum contraction. Cumulative log-dose response curves for analogues of serotonin demonstrated a high degree of specificity for the serotonin receptor and large nonphysiological concentrations of serotonin caused relaxation of the contracted artery. Extracellular calcium was shown to be an absolute requirement for serotonin-induced contractions. Extracellular magnesium, in contrast, was shown to inhibit serotonin-induced contractions.

Animals↗