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Biomedical subjects

L M Henderson

Publications and source records attributed to L M Henderson.

At least 73 records · Page 4Linked to original sources
PubMed1984

Effect of binding to hemoglobin and albumin on pyridoxal transport and metabolism.

Scatchard plot analysis indicated that pyridoxal binds to hemoglobin more than twice as tightly as it does to serum albumin. Comparison of the formation constants for hemoglobin and albumin, using standard competitive binding equations, indicated that the distribution ratio for pyridoxal between erythrocytes and plasma should be 6.5:1. This distribution was approximately the same as that observed when pyridoxal was incubated with whole human blood, suggesting that these two proteins are the primary determinants of the pyridoxal distribution in whole blood. With in situ perfused rat liver the uptake of [3H] pyridoxal from the perfusate was reduced by the inclusion of erythrocytes in the perfusate. This was reflected in the decreased production of 4-pyridoxic acid by the perfused liver from 3.8% to 1.2% of the dose by the addition of erythrocytes to the perfusate. The major labeled metabolites found in the liver were pyridoxal phosphate, pyridoxamine phosphate, and 4-pyridoxic acid for both types of perfusion. In intact animals, reduction of the erythrocytes concentrations to hematocrits of 30-40% increased the recovery in the urine of 3H from administered [3H] pyridoxal from control values of 27-35% to 40-50% of the dose within 48 h. Half of the label in urinary metabolites was in 4-pyridoxic acid.

Animals↗
PubMed1984

Transport and metabolism of pantothenic acid by rat kidney.

Transport of [14C]pantothenic acid was studied using brush-border membrane vesicles prepared from rat kidney. In the presence of a Na+ gradient an accumulation of pantothenic acid 3-fold above equilibrium was observed. The Km and Vmax found were 7.30 microM and 23.8 pmol/mg protein per min, respectively. Isolated perfused rat kidneys were employed to study excretion of pantothenic acid at various concentrations in the perfusate. At physiological plasma concentrations, the filtered pantothenic acid was largely reabsorbed by the active process observed in the vesicles. At higher concentrations, pantothenic acid was found to undergo tubular secretion. Penicillin inhibited this secretory process indicating that both compounds share a secretory mechanism. Live animal studies indicated that the only compound excreted after injection of [14C]pantothenic acid was free pantothenic acid. After 1 week only 38% of the administered dose was excreted in the urine, indicating that effective conservation was taking place in the whole animal.

Animals↗
PubMed1984

Effect of vitamin C deficiency on hydroxylation of trimethylaminobutyrate to carnitine in the guinea pig.

The effect of ascorbate deficiency on carnitine biosynthesis was investigated in young male guinea pigs. Liver and skeletal muscle carnitine levels were reduced in scorbutic animals. Heart and kidney concentrations remained unchanged. 14C-labeled 4-N-trimethylaminobutyrate was administered to control, pair-fed and scorbutic animals and distribution of isotope in compound present in the liver after 30 min was determined. Control and pair-fed animals converted trimethylaminobutyrate to carnitine faster than scorbutic animals. Injection of ascorbate with the [14C]trimethylaminobutyrate reversed the decline in trimethylaminobutyrate hydroxylase (EC 1.14.11.1) activity in scorbutic animals.

Animals↗
PubMed1984

Absorption and metabolism of adenine, adenosine-5'-monophosphate, adenosine and hypoxanthine by the isolated vascularly perfused rat small intestine.

Intestinal vascular perfusion and in vivo live animal experiments were conducted in order to evaluate the nature and extent of the intestinal metabolism of adenine, adenosine, adenosine-5'-monophosphate (AMP) and hypoxanthine in the rat. Radiolabeled purine substrates were administered intralumenally. Intestinal contents, tissue and/or portal flow were collected and evaluated for resultant purine metabolites by liquid and paper chromatography and paper electrophoresis. Adenosine, AMP and hypoxanthine were quantitatively metabolized to end products (primarily uric acid) within 15 minutes after administration. In contrast, the metabolism of adenine to uric acid was considerably slower. Up to 20% of the administered adenine was recovered unmetabolized in the portal vasculature. Nonetheless uric acid was the primary metabolite recovered from the portal circulation in the isolated intestine regardless of the purine substrate or concentration administered. Since lumenal inosine concentrations rose sharply with increasing doses of AMP, either transport or metabolism of inosine is a rate-limiting step in the intestinal metabolism of purines to uric acid in the rat. Finally, the large percentage of the radiolabel in uric acid recovered in the lumen is consistent with the hypothesis that the intestine is an extrarenal site for purine excretion.

Absorption↗
PubMed1983

Pyridine nucleotide synthesis in normal and neoplastic human pituitary cells in culture.

14C-Nicotinic acid (NA) incorporation into nicotinamide adenine dinucleotide (NAD) was studied in cultures from 7 normal human pituitaries and 13 chromophobe adenomas. 14C-NA (7.2 microM) was incubated with both normal and tumor cell cultures for periods up to 48 hours. Cells and culture media were examined separately for metabolites at 24 and 48 hours. NAD was the major labeled metabolite found in both normal and tumor cells, accounting for 65.4% for normal cells and 56.8% for tumor cells of the total cellular label at 48 hours. Nicotinamide (NAm), a product arising from NAD, was the only labeled metabolite found in the culture medium, aside from the 14C-NA added initially. Total incorporation of 14C-NA into NAD was estimated by adding the cellular 14C-NAD and labeled products of NAD (NMN, NAm and NADP) to the 14C-NAm found in the medium for each culture. Cultures derived from adenomas demonstrated greater than twice the rate of incorporation of 14C-NA into NAD as did normal cell cultures (P less than 0.01 at 24 hours and less than 0.001 at 48 hours). This difference did not appear to be related to the secretory status of the tumor, since both secreting and nonsecreting tumors demonstrated increased rates when compared to normal cells. This difference also persisted in two different culture media and with cells that had been maintained in culture for different lengths of time (6-day dispersed cell cultures and 6- to 16-week fragment cultures).

Adenoma, Chromophobe↗
PubMed1983

Hydrolysis and absorption of pantothenate and its coenzymes in the rat small intestine.

The transport of pantothenate by the rat small intestine occurs by simple diffusion. There was no significant difference in the rate of pantothenate absorption in the upper, middle or lower sections of the intestine. Coenzyme A was hydrolyzed to pantetheine and pantothenate in the intestinal lumen via the following series of reactions: coenzyme A leads to phosphopantetheine leads to pantetheine leads to pantothenate. Intestinal tissue, which contains high levels of pantetheinase, quickly degrades pantetheine to pantothenate, which is then transported to the blood and thence to other tissues. Tissue distribution patterns of 14C 5 hours after intraluminal administration of 14C-labeled coenzyme A or [14C]pantothenate were similar; approximately 40% of the 14C was present in muscle and 10% in liver.

Absorption↗
PubMed1983

Digestion and absorption of NAD by the small intestine of the rat.

A number of preparations of varying complexity have been used in an effort to elucidate the reactions by which NAD is hydrolyzed to nicotinamide during intestinal digestion. NAD labeled with 14C in the adenine or pyridine moiety was the substrate used with perfused rat intestine, live rats, perfused live rats, with collection of portal flow, intestinal contents, mucosal tissue, or pancreatic juice. The conclusions reached are that a pyrophosphatase present in the intestinal juice and to a much lesser extent in the pancreatic juice releases 5'-AMP and nicotinamide ribonucleotide. The 5'-AMP was rapidly converted to adenosine then to inosine by bacteria-free intestinal contents. Perfused or intact intestine rapidly hydrolyzed NMN to nicotinamide riboside, which accumulated, but was not absorbed. It was slowly cleaved by an enzyme associated with the mucosal cells to nicotinamide, which was the major if not the only labeled compound absorbed.

Animals↗
PubMed1983

A neurosurgical Munchausen tale.

The travels of a young man feigning subarachnoid haemorrhage in London and Scotland, over the past year, are documented. The origins of the Munchausen Tales are reviewed.

Adult↗
PubMed1983

Niacin.

Explore the source record for details and available documents.

Absorption↗
PubMed1982

The binding of pyridoxal to hemoglobin.

Concentrative uptake of pyridoxal by human erythrocytes has been investigated using a rapid mixing technique with 3H-labeled pyridoxal. A nonsaturable, initial influx of [3H]pyridoxal into the erythrocyte indicated passive diffusion. Since pyridoxal will form Schiff bases reversibly with amino acids, the possibility of binding to intracellular proteins was examined. Exposure of erythrocytes to pyridoxal followed by NaBH4 reduction, resulted in a stable pyridoxyl-protein complex. The binding site for pyridoxal was found to be on the alpha chain of oxyhemoglobin, as determined by ion exchange chromatography and amino acid analysis. Separation of the tryptic peptides from the [3H]pyridoxyl-alpha chain on Dowex 50 and analysis of the [3H] pyridoxal peptide showed that the binding site of pyridoxal was the NH2-terminal valine. Pyridoxal was also found to bind to the alpha chain of nonoxygenated hemoglobin. The rate of pyridoxyl-hemoglobin formation in a cell-free system provided additional evidence in support of the suggestion that concentrative uptake of pyridoxal by human erythrocytes is due to intracellular binding of pyridoxal to hemoglobin. Pyridoxal phosphate and glucose, which also bind to the NH2-terminal valine, did not reduce the accumulation of pyridoxal in the erythrocyte.

Amino Acids↗
PubMed1982

Mammalian enzymes of trimethyllysine conversion to trimethylaminobutyrate.

The biosynthesis of carnitine proceeds from trimethyllysine (TML) by beta-hydroxylation by a liver or kidney mitochondrial enzyme, which requires oxygen, alpha-ketoglutarate, ferrous iron, and ascorbate. This dioxygenase is rapidly inactivated by preincubation with Fe2+, but not Fe3+. The evidence suggests that superoxide anion is involved in the hydroxylation. beta-Hydroxytrimethyllysine undergoes aldol cleavage to glycine and trimethylaminobutyraldehyde under the influence of serine hydroxymethyltransferase and possibly a specific aldolase. The next step, the aldehyde oxidation, is catalyzed by a specific NAD-dependent aldehyde dehydrogenase from liver cytosol. The product, trimethylaminobutyrate, is then hydroxylated by a cytosolic dioxygenase to carnitine. This enzyme, which has the same cofactor requirements as TML hydroxylase, is found in the liver of all species examined, but is absent from the kidney of some species.

Aldehyde Oxidoreductases↗
PubMed1981

Effect of ascorbic acid deficiency on the in vivo synthesis of carnitine.

The effects of ascorbate deficiency on carnitine biosynthesis was investigated in young male guinea pigs. Liver and kidney carnitine levels were not affected by the deficiency, but scorbutic animals had 50% less carnitine in heart and skeletal muscle than control animals. Labeled carnitine precursors, 6-N-tri-methyl-L-lysine and 4-N-trimethylaminobutyrate, both of which require ascorbate for their enzymatic hydroxylation, were injected into the vena cava of control, pair-fed and scorbutic animals. The distribution of isotope in compounds present in the liver and kidney after 1 h was determined. The uptake of trimethyllysine by the liver was less than 2% in 1 h, while the kidney took up approx. 20% of the 14C. Control and pair-fed animals converted trimethyllysine to kidney trimethylaminobutyrate 8--10 times as well as did scorbutic animals. Trimethylaminobutyrate hydroxylase, present in the liver but almost absent from the kidney, converted nearly all of substrate taken up by the liver to carnitine in both the scorbutic and control animals.

Animals↗
PubMed1981

Aneuploid spermatocyte frequency in domestic sheep heterozygous for three Robertsonian translocations.

In an analysis of the chromosomes in 332 metaphase II figures from 3 triple heterozygous rams (51,xy,t1t2t3) and a further 84 figures from 3 normal rams (54,xy), there were no hypermodal cells in the normal rams but 9 such cells were found in the triple heterozygotes, giving a mean aneuploid frequency of 5.42% which was similar to the levels previously found in the single heterozygotes. Forty hypomodal cells were found in the 6 rams of which a number would have lost chromosomes due to lagging at anaphase I. Individual variation in the aneuploid metaphase II frequency was observed in the triple heterozygotes. A significant surplus of secondary spermatocytes of normal karyotype and a deficit of 25,t1t3 were found in the metaphase II figures from the triple heterozygotes. There was also a significant increase of normal progeny and a deficit of 52,t1t3 and 53,t2 progeny from the matings of triple heterozygous rams and normal ewes. It is possible that the significantly uneven distribution of segregation products in the triple heterozygotes might have been the result of either cell selection or degeneration during spermatogenesis.

Aneuploidy↗
PubMed1980

Transport and accumulation of pyridoxine and pyridoxal by erythrocytes.

The mechanisms of transport of pyridoxine (PN) and pyridoxal (PL) into erythrocytes have been investigated using the rapid-mixing technique with 3H-labeled substrates. Erythrocytes take up PN by passive diffusion as indicated by the fact that the initial influx process is nonsaturable and is not affected by pyridoxamine (PM), PL, or 4'-deoxypyridoxine. Transport of PL has the same characteristics. The transport of both PN and PL is temperature-dependent with a sharp increase in rate of uptake between 15 and 20 degrees C. The accumulation of 3H from [3H]PN against a concentration gradient was the result of phosphorylation. When the phosphorylation of [3H]PN was reduced by adding 160 microM unlabeled PN, PL, PM, or 4'-deoxypyridoxine, the cell:medium concentration ratio for 3H did not exceed unity. In contrast, with [3H]PL, 1.6 mM concentrations of these unlabeled substrates did not reduce the cell:medium concentration ratio of 3H. This kinase-in-dependent accumulation of PL against a concentration gradient, in the absence of evidence for mediated transport, suggested that binding by an intracellular protein was responsible. Evidence for such binding was obtained from Sephadex G-75 gel filtration, ultrafiltration, and equilibrium dialysis studies with [3H]PL. Reduction of the PL x protein complex with NaBH4 resulted in a stable pyridoxyl protein. The high binding capacity and the molecular weight by gel filtration suggest that hemoglobin is the binding protein.

Animals↗
PubMed1980

Transport and metabolism of pyridoxine in rat liver.

Evidence, obtained with in situ perfused rat liver, indicated that pyridoxine is taken up from the perfusate by a non-concentrative process, followed by metabolic trapping. These conclusions were reached on the basis of the fact that at low concentrations (0.125 microM), the 3H of [3H]pyridoxine accumulated against a concentration gradient, but high concentrations (333 microM) of pyridoxine or 4-deoxypyridoxine prevented this apparent concentrative uptake. Under no conditions did the tissue water:perfusate concentration ratio of [3H]pyridoxine exceed unity. The perfused liver rapidly converted the labeled pyridoxine to pyridoxine phosphate, pyridoxal phosphate and pyridoxamine phosphate and released a substantial amount of pyridoxal and some pyridoxal phosphate into the perfusate. Since muscle and erythrocytes failed to oxidize pyridoxine phosphate to pyridoxal phosphate, it is suggested that the liver plays a major role in oxidizing dietary pyridoxine and pyridoxamine as their phosphate esters to supply pyridoxal phosphate which then reaches to other organs chiefly as circulating pyridoxal.

Absorption↗