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Biomedical subjects

D S Brown

Publications and source records attributed to D S Brown.

At least 19 recordsLinked to original sources
PubMed1998

Transfers of N metabolites across the ovine liver in response to short-term infusions of an amino acid mixture into the mesenteric vein.

The effect of acute (4.5 h) infusions into the mesenteric vein of an amino acid (AA) mixture, which simulated the composition of rumen microbial protein, on net transfers of NH3, urea and total AA across the portal-drained viscera (PDV) and liver in the ovine has been examined. Four wether sheep were surgically prepared with vascular catheters across the PDV and liver (Lobley et al. 1995) and were offered a basal diet of 1000 g grass pellets/d (approximately 1.4 x energy maintenance). Each animal was infused at weekly intervals with one of four dilutions of the AA mixture. These dilutions provided 0.44, 0.88, 1.32 and 1.84 mmol AA-N/min infused, the lowest of which approximately doubled the net absorption of AA-N from the basal diet. Animals were treated with heparin to allow continuous collection of blood by peristaltic pump for 2 h preceding, and between 0.5-2.5 and 2.5-4.5 h after, the start of the AA infusions. Blood flow in the hepatic artery increased (100 v. 208 g/min; P = 0.002) in response to AA infusion, while hepatic portal venous flow decreased (2090 v. 1854 g/min; P = 0.006). The AA infusion also stimulated O2 uptake by the PDV (P < 0.001) and liver (P = 0.016). Absorption across the PDV and hepatic removal of NH3 were unchanged between basal and amino acid infusion conditions. Urea-N removal across the PDV was unaltered, but hepatic production increased (P < 0.001) with level of AA infusion. During infusions, net appearance of AA across the PDV was below the theoretical level. This may have been due to inhibition of AA uptake from the small intestine, and/or increased removal by the digestive tract of AA from the systemic circulation associated with greater arterial concentrations. Hepatic extraction of AA increased with level of infusion, both for total AA and those included in the infusate. Total hepatic urea-N production tended towards a maximum (estimated as 2 mumol N/g liver wet weight per min). The AA removed by the liver and not used for ureagenesis remained similar (170 mumol AA-N/min) between basal and AA infusions. This was presumed available for anabolic purposes (mainly synthesis of export proteins). The proportion of net AA-N appearance (absorption plus infused) across the PDV removed by the liver declined from 0.71 to 0.53 between basal and AA infusions. In contrast to findings from cattle (Wray-Cahen et al. 1997), increased AA infusion did not alter the net removal of glutamine across the liver. This may reflect differences between the studies in NH3: AA-N absorbed. Further differences between the cattle study and the current findings may relate to the different physiological state (pregnancy v. growth), which may alter the partition of AA between anabolic and catabolic fates.

Amino Acids↗
PubMed1998

Putrescine as a source of instant energy in the small intestine of the rat.

BACKGROUND AND AIMS: It has been suggested that putrescine acts as a growth factor in the gut, but its exact function in some aspects of cellular metabolism is still in question. The aim of the present work was to identify some functions of putrescine in small bowel metabolism. ANIMALS: Rats (about 80 g), in groups of five, were given either phytohaemagglutinin- or lactalbumin-containing diets, fed ad libitum or were fasted for 48 hours and re-fed for six or twelve hours before being killed. METHODS: Uptake of intraperitoneally or intragastrically administered [14C]putrescine and its conversion to succinate by the rat small bowel mucosa was measured. Tissue polyamine and succinate contents were measured by high performance liquid chromatography and amino acid analysis respectively. RESULTS: Uptake of putrescine by the small bowel mucosa from the systemic circulation and conversion of about 30% of this to succinate occurs in the epithelium of the healthy small bowel. Compared with rats given food ad libitum, putrescine uptake was doubled in fasted animals and more than 70% of it was converted to succinate. All these changes returned to control values on refeeding. Using phytohaemagglutinin induced gut growth as a model, the uptake of putrescine from the systemic circulation by the serosal side of the small intestinal epithelium was increased immediately after growth was stimulated. During phytohaemagglutinin induced growth of the gut, putrescine was converted to succinate in the same proportion as in the healthy small bowel. CONCLUSIONS: The experiments identified a novel function for putrescine in gut metabolism: it can be used as an instant energy source when required.

Analysis of Variance↗
PubMed1997

Intracellular levels of polyamines in Krebs II lymphosarcoma cells in mice fed phytohaemagglutinin-containing diets are coupled with altered tumour growth.

The number of Krebs II tumour cells recovered from the ascitic fluid of mice fed for 8 days on a lactalbumin (La) control diet was about three times higher than that in animals fed a phytohaemagglutinin-containing (PHA) diet. Feeding a PHA diet for less than 8 days after tumour cell injection also led to a reduction in tumour cell growth. There was an apparent inverse relationship between the total tumour cell count and the intracellular content of putrescine, spermidine and spermine. Hyperplasia of the small intestine occurred in the mice during the development of the ascites. A series of other organs were not affected in the same manner. The results indicate that the polyamine content of Krebs II ascites cells must increase by more than three-fold in order to achieve the intracellular concentration necessary to be able to enter the S-phase. A partial synchronization of the tumour cell population is suggested. Hyperplastic growth of the small intestine would appear to compete with tumour cells for polyamines from a common body pool.

Animals↗
PubMed1997

Hepatic response to increased exogenous supply of plasma amino acids by infusion into the mesenteric vein of Holstein-Friesian cows in late gestation.

The hepatic responses of late gestation, dry dairy cows to acute (6 h) infusions of an amino acid (AA) mixture (Synthamin; 0.0, 1.1, 2.2, 4.4, 8.8 and 17.6 mumol/min) into the mesenteric vein were determined. Neither blood flow nor O2 consumption across the portal-drained viscera (PDV) and liver was significantly altered by infusion. Similarly, there were no effects on net absorption, or hepatic removal, of acetate, propionate, butyrate or NH3. Glucose PDV appearance was unchanged but hepatic glucose production increased (P = 0.032) by 0.2 mumol/min per mumol/min of AA infused. Additional extraction of alanine, glycine (both infused) and glutamine (not infused) by the liver was sufficient to account for most of the extra C required for glucose synthesis. The N that would be liberated from these glucogenic AA would also account for a large proportion of the increase in urea-N produced in response to the AA infusion. This supports the concept of a correlation between gluconeogenesis and ureagenesis. Furthermore, the amide-N liberated from the extracted glutamine would contribute up to 0.17 of hepatic NH3 flux and assist in balancing N inputs into the carbamoyl phosphate and arginosuccinate entry points of the ornithine cycle. Rates of fractional extraction of the various AA by the liver were best fitted by linear equations, indicating that even at the highest rates of administration (approximately twice maximal physiological absorption) the transport systems were not saturated. Hepatic fractional extractions of infused essential AA were highest for methionine (0.83) and phenylalanine (0.87) with the lowest proportion removed observed for valine (0.25), leucine (0.30), lysine (0.31) and isoleucine (0.49). For the non-essential AA, the highest apparent fractional extractions were for glycine (0.73), arginine (0.79) and tyrosine (0.63) followed by alanine (0.54), proline (0.47) and serine (0.37). Hepatic removal of AA-N exceeded the increase in urea-N formation such that, at the highest rate of infusion, approximately 10 mmol/min of the extracted AA was apparently available for hepatic anabolism, more than is required to account for assumed increases in liver mass and export protein synthesis. Similarly, the amount of AA available for peripheral tissue protein gain, when assessed against phenylalanine supply as the limitation, would be the equivalent of a maximum of 0.5 g protein retained/min (6 mmol AA-N/min). This would provide sufficient AA for replenishment of peripheral (muscle) protein stores plus support of the placenta and fetus.

Amino Acids↗
PubMed1997

Amino acid use by the gastrointestinal tract of sheep given lucerne forage.

Essential amino acid (EAA) utilization by gastrointestinal tract (GIT) tissues has been investigated in sheep given 800 and 1,200 g/day lucerne pellets. Animals prepared with indwelling catheters into the aorta and the portal drained viscera plus cannulas into the small intestine were infused with mixed U-13C-labeled amino acid or (1-13C]leucine tracers into the jugular vein or directly into the small intestine. GIT sequestration of EAA from arterial and luminal AA pools was determined from tracer and tracee arterioportal concentration differences at both levels of intake. Proportional tracer 13C-labeled EAA extraction of the arterial supply, on first pass across the GIT during jugular infusion, ranged from 0.063 for histidine to 0.126 for leucine. Recovery of intestinally infused tracer 13C-EAA at the portal vein ranged from 0.61 for histidine to 0.83 for valine. These data were independent of intake. Calculated rates of tracee sequestration by GIT tissues represented 0.45-0.65 of whole body EAA flux, except for histidine, for which the values were much lower (0.25-0.32). With the exception of phenylalanine, more than 0.8 of the EAA used by the GIT was extracted from circulating blood, thus calling into question the theory that GIT tissues make preferential use of EAA during absorptive metabolism, restricting supply to peripheral tissues such as skeletal muscle (growth) or mammary glands (lactation). Instead the GIT seems to compete very successfully with these tissues for circulating blood EAA.

Amino Acids, Essential↗
PubMed1997

Absorption of amino acids from the intestine and their net flux across the mesenteric- and portal-drained viscera of lambs.

Experiments were conducted to compare the rates of apparent absorption (disappearance) of individual essential amino acids (EAA) from the small intestine with their net fluxes across the mesenteric- (MDV) and portal- (PDV) drained viscera in sheep given a pelleted alfalfa diet at two levels of intake. Disappearances of individual EAA across the region of the small intestine drained by the mesenteric arcade (jejunum to ileum) were similar to those across the whole of the small intestine (duodenum to ileum). The net MDV flux of each EAA was similar to its rate of disappearance, but, with the exception of threonine on the low intake level, the net PDV flux was lower (P < .05). Increasing the intake of alfalfa from 800 to 1,200 g/d increased the rate of disappearance of individual EAA between the duodenum and ileum by .56 (range .43 to .65) and between the jejunum and ileum by .51 (range .45 to .60). The MDV and PDV blood flows increased by .35 and .39, respectively, and, with the exception of valine, net fluxes of individual EAA increased by .39 (range .20 to .50) across the MDV and by .44 (range .21 to .71) across the PDV. When net fluxes across the MDV and PDV were measured simultaneously, the ratio of PDV: MDV flux for each EAA was less than (P < .05) unity (mean .61, range .55 to .69), even though all MDV blood enters the PDV, contributing approximately .45 of the total portal flow. This observation suggests that, in regions of the tract not drained by the MDV, extraction of arterial blood EAA for tissue and secretory protein synthesis must exceed the release of protein degradation products into the venous drainage. The results are discussed in terms of endogenous protein secretions into the lumen of the tract anterior to the small intestine.

Amino Acids, Essential↗
PubMed1996

Specific inhibition of epidermal growth factor receptor tyrosine kinase by 4-anilinoquinazolines.

Since the mitogenic action of EGF is mediated by ligand-induced autophosphorylation of the EGF receptor (EGFR), and EGFR is commonly overexpressed in solid human tumours, inhibitors of receptor tyrosine kinase activity (RTK) could prove to be effective antitumour agents. Screening of a compound library using an EGF-RTK enzyme prepared from human tumour derived A431 cells identified a series of potent (IC50 < 1 microM) enzyme inhibitors. These inhibitors are quinazolines bearing a variety of substituted anilines at the 4-position. The most potent 4-anilinoquinazolines (IC50 approximately equal to 20 nM) have small non-polar meta substituents on the aniline ring, and are competitive with ATP and non-competitive with substrate. The growth inhibitory activity of these agents was assessed in vitro using KB cells (human oral squamous tumour) grown in the absence or presence of EGF. A selected compound, 4-(3-chloroanilino)quinazoline (CAQ), inhibited EGF-stimulated growth in a concentration dependent manner and complete blockade was observed at concentrations (1-10 microM) which had no effect on basal growth. Selectivity of growth inhibition by CAQ was further exemplified in IGF1-stimulated KB cells where no effect was detected at concentrations which completely blocked EGF-stimulated growth. Similarly, CAQ blocked TGF alpha-stimulated growth in MCF-7 human breast cancer cells without affecting insulin-stimulated growth. These studies define a novel class of EGF-RTK inhibitors which are also potent and selective inhibitors of EGF-stimulated human tumour cell growth in vitro.

Antineoplastic Agents↗
PubMed1996

Potato lectin: a three-domain glycoprotein with novel hydroxyproline-containing sequences and sequence similarities to wheat-germ agglutinin.

Potato (Solanum tuberosum) tuber lectin is a chitin-binding, hydroxyproline-rich glycoprotein, which may be involved in the defence mechanism of the plant. We had previously obtained evidence that it consists of at least two very dissimilar domains. The aim was to use a combination of accurate determinations of molecular weight and protein sequencing to gain more accurate information on the domains. Accurate determinations of the molecular weight of the lectin by a MALDI mass spectrometer have shown that the subunit molecular weight is 65,500 (+/- 1100) and that of a totally deglycosylated sample is 31,250 (+/- 30). This means that the lectin is 52.3 (+/- 1)% carbohydrate with a considerable number of glycoforms being present. Partial sequences and other analyses are consistent with the existence of three distinct domains. These are: (1) an N-terminal region which is rich in proline but poor in hydroxyproline; (2) a glycosylated region with a glycosylated molecular weight of 45,300 (+/- 1100) and a deglycosylated molecular weight of 11,050 (+/- 50) which is extremely rich in glycosylated hydroxyproline residues with a similar sequence to extensins; and (3) a cystine-rich domain which has the sugar binding site shows partial conservation of a repeated motif common to many chitin-binding proteins of the hevin family including wheat-germ agglutinin. The closest similarity seems to be to the sequence of potato basic chitinase.

Amino Acid Sequence↗
PubMed1996

The fate of absorbed and exogenous ammonia as influenced by forage or forage-concentrate diets in growing sheep.

Changes in splanchnic energy and N metabolism were studied in sheep, prepared with vascular catheters across the portal-drained viscera (PDV) and the liver, and maintained on supramaintenance intakes of either gross or grass + barley pellets. The animals were challenged, on both diets, with 4 d intramesenteric vein infusions of NH4Cl (25 mumol/min) plus NH4HCO3 (at either 0 or 125 mumol/min). On the final day of each treatment the natural abundance NH4Cl was replaced with 15NH4Cl over a 10 h infusion while over the same period [1-13C]leucine was infused via a jugular vein. Measurements were made of blood flow plus mass transfers of NH3, urea, free amino acids and O2 across the PDV and liver. Enrichments of [14N15N]urea and [15N15N]urea plus [15N]glutamine, aspartate and glutamate were also monitored. Whole-body urea flux was determined by infusion of [14C]urea. At the end of the study the animals were infused for 3 h with 15nH4Cl, killed and liver samples assayed for intracellular free amino acid enrichments and concentrations. Blood flows across the splanchnic region were unaffected by either diet or level of ammonium salt infusion. At the lower ammonium salt infusion there was a trend for greater absorption of NH3 across the PDV (P < 0.10) with grass + barley than with the grass diet, while removal of urea was unaltered. At the higher ammonium salt infusions there was a significantly greater appearance of NH3 across the PDV and this exceeded the extra infused. Urea-N removal, however, was also elevated and by more than that required to account for the additional NH3. The PDV contributed 19-28% to whole-body O2 consumption and the liver 23-32%. Hepatic extraction of absorbed NH3 was complete on all treatments and systemic pH remained constant. The fractions of urea-N apparently derived from NH3 were similar on the grass (0.50-0.64) and grass + barley (0.64-0.67) diets. Hepatic production of urea agreed well with urea flux measurements. Between the two levels of ammonium salt infusion and within diets the additional NH3 removed across the PDV was accounted for by the increased urea-N production. The [14N15N]:[15N15N] ratio of the urea produced was 97:3, while the enrichment of hepatic intracellular free aspartate was lower than that of [14N15N]urea. Glutamine enrichments were 0.23-0.37 those of [14N15N]urea, indicating a minor role for those hepatocytes (probably perivenous) which contain glutamine synthetase (EC 6.3.1.2). Leucine kinetics, either for the whole body or splanchnic tissues, were not different between diets or level of ammonium salt infusion, except for oxidation which was less on the grass + barley ration. Amino acid concentrations were lower on the grass + barley diet but net PDV absorptions were similar. The pattern of essential amino acids absorbed into the PDV showed good agreement with the published composition of mixed rumen microbial protein. Fractional disappearances of absorbed free essential amino acids across the liver varied from 0.4 (branched chains) to near unity (histidine, phenylalanine).

Amino Acids↗
PubMed1996

Splanchnic-bed transfers of amino acids in sheep blood and plasma, as monitored through use of a multiple U-13C-labelled amino acid mixture.

The response in whole-body and splanchnic tissue mass and isotope amino acid transfers in both plasma and blood has been studied in sheep offered 800 g lucerne (Medicago sativa) pellets/d. Amino acid mass transfers were quantified over a 4 h period, by arterio-venous procedures, across the portal-drained viscera (PDV) and liver on day 5 of an intravenous infusion of either vehicle or the methylated products, choline (0.5 g/d) plus creatine (1.0 g/d). Isotopic movements were monitored over the same period during a 10 h infusion of a mixture of U-13C-labelled amino acids obtained from hydrolysis of labelled algal cells. Sixteen amino acids were monitored by gas chromatography-mass spectrometry, with thirteen of these analysed within a single chromatographic analysis. Except for methionine, which is discussed in a previous paper, no significant effects of choline plus creatine infusion were observed on any of the variables reported. Whole-body protein irreversible-loss rates ranged from 158 to 245 g/d for the essential amino acids, based on the relative enrichments (dilution of the U-13C molecules by those unlabelled) of free amino acids in arterial plasma, and 206-519 g/d, when blood free amino acid relative enrichments were used for the calculations. Closer agreement was obtained between lysine, threonine, phenylalanine and the branched-chain amino acids. Plasma relative enrichments always exceeded those in blood (P < 0.001), possibly due to hydrolysis of peptides or degradation of protein within the erythrocyte or slow equilibration between plasma and the erythrocyte. Net absorbed amino acids across the PDV were carried predominantly in the plasma. Little evidence was obtained of any major and general involvement of the erythrocytes in the transport of free amino acids from the liver. Net isotope movements also supported these findings. Estimates of protein synthesis rates across the PDV tissues from [U-13C] leucine kinetics showed good agreement with previous values obtained with single-labelled leucine. Variable rates were obtained between the essential amino acids, probably due to different intracellular dilutions. Isotope dilution across the liver was small and could be attributed predominantly to uni-directional transfer from extracellular sources into the hepatocytes and this probably dominates the turnover of the intracellular hepatic amino acid pools.

Amino Acids↗
PubMed1996

Monitoring of median nerve somatosensory evoked potentials during cervical spinal cord decompression.

We evaluated the intraoperative utility of monitoring median nerve somatosensory evoked potentials (SEPs) in 31 consecutively hospitalized neurosurgical patients (mean age 55.3 +/- 2.1 years) who underwent spinal cord decompression for cervical herniated disc, spondylosis, or tumor. Pre- and postoperative standard neurological examinations included evaluation of motor function, sensory responses, gait, tone, and reflexes. Evoked potentials were recorded from clavicular Erb's (N9) and contralateral cortical (N20) points. Intraoperatively, SEP measurements were obtained after the onset of anesthesia (baseline control) and were repeated throughout the operative procedures. N20 and N9-N20 conduction latencies were measured for each SEP recording; disappearance of the SEP waveform was interpreted as a nonquantifiable increase in latency. Follow-up neurological examinations were made immediately after and up to 6 months following surgery. Postoperatively, the 31 study subjects were assigned to one of two groups based on neurological evaluation: 27 group I subjects had either no change or improvement (good outcome) whereas four group II subjects had postoperative neurological deterioration (poor outcome). Intraoperative N9-N20 interpeak latency was found to increase during cervical decompression in six of 27 group I and in two of four group II subjects. Only two of the Group I subjects exhibited increases > 10% (14 and 19%, respectively). Intraoperative communication to the surgeon of a marked increase of N9-N20 latency during positioning for cervical traction clearly obviated a poor outcome in one group I subject; Upon removal of traction, latency decreased and significant changes in neurological function were not detected postoperatively. The SEP waveform disappeared in two of the group II and in none of the group I subjects. In the two group II subjects exhibiting increases of N9-N20 latencies, increments were > 20%. These findings indicate that in patients undergoing cervical spinal cord decompression, disappearance of SEPs or increases > 20% in the N9-N20 interpeak latency are suggestive of operative conditions that place patients at risk for poor neurological outcome.

Adult↗
PubMed1996

Polyamine metabolism of enterocyte-like Caco-2 cells after exposure to Phaseolus vulgaris lectin.

The effect of Phaseolus vulgaris isolectin E4 on polyamine concentrations and ornithine decarboxylase activity of proliferating and differentiating Caco-2 cells was investigated. Values of putrescine, spermidine, and spermine in control cells were highest during the early phase of proliferative cell growth and lowest in the stationary phase. Phytohaemagglutinin E4 significantly increased cellular polyamine values during the late proliferative phase of cell growth. Ornithine decarboxylase activity was high during intensive proliferation and growth, but was lower when proliferation slowed down or ceased. Exposure of Caco-2 cells in the early proliferative phase of cell growth to increasing concentrations of the potent intestinal growth factor phytohaemagglutinin E4 greatly stimulated enzyme activity. In contrast, the activity of ornithine decarboxylase was not stimulated in Caco-2 cells of the late proliferative phase nor was there any increase in the enzyme activity in differentiating and fully differentiated cells of the stationary phase. Accordingly, when proliferating Caco-2 cells possessed the highest ornithine decarboxylase activity, the polyamine values were also at their highest. During differentiation, as the ornithine decarboxylase activity fell close to zero, polyamine values also decreased. In the early proliferative phase of cell growth ornithine decarboxylase activity coincided with DNA synthesis in cells exposed to Phaseolus vulgaris isolectin E4. These findings with Caco-2 cells were similar to those found in brush border cells of the rat small intestine.

Biogenic Polyamines↗
PubMed1995

Switching between control and phytohaemagglutinin-containing diets affects growth of Krebs II ascites cells and produces differences in the levels of putrescine, spermidine and spermine.

Almost twice as many ascites tumour cells were recovered from mice pre-fed for 3 days on a lactalbumin (La)-based control diet, injected with Krebs II ascites cells and then maintained on the same diet for a further 8 days, when compared with mice fed on a phytohaemagglutinin-containing (PHA) diet for the whole period. A dietary switch on the day of injection of tumour cells produced an intermediate effect; mice switched to the La diet after pre-feeding on PHA for 3 days developed somewhat more tumour cells than when the opposite dietary switch was performed. The polyamine content in the tumour cells was lowest in the mice fed on La, and highest in mice fed PHA for the duration of the experiment, respectively. Since large amounts of extraneous polyamines are required in order to sustain tumour growth, and the hyperplastic growth of the gut which occurs in response to injesting the lectin is a polyamine-dependent process, it is evident that the two growth signals compete with one another for important nutrients/growth factors, including polyamines.

Animals↗
PubMed1995

Rapid high-performance liquid chromatographic method for the quantitation of polyamines as their dansyl derivatives: application to plant and animal tissues.

A rapid high-performance liquid chromatographic method for the separation of polyamines as their dansyl derivative has been developed. The chromatographic system used consisted of a reversed-phase column and a mobile phase of acetonitrile and water. The separation of 1,3-diaminopropane, putrescine, cadaverine, spermidine and spermine takes only 9 min. This method provides a good resolution between 1,3-diaminopropane and putrescine. It has been applied to quantify polyamines from seeds of wheat, petals of Phalaenopsis hybrids and various rat tissues.

Animals↗
PubMed1995

Hepatic detoxification of ammonia in the ovine liver: possible consequences for amino acid catabolism.

The effects of either low (25 mumol/min) or high (235 mumol/min) infusion of NH4Cl into the mesenteric vein for 5 d were determined on O2 consumption plus urea and amino acid transfers across the portal-drained viscera (PDV) and liver of young sheep. Kinetic transfers were followed by use of 15NH4Cl for 10 h on the fifth day with simultaneous infusion of [1-13C]leucine to monitor amino acid oxidation. Neither PDV nor liver blood flow were affected by the additional NH3 loading, although at the higher rate there was a trend for increased liver O2 consumption. NH3-N extraction by the liver accounted for 64-70% of urea-N synthesis and at the lower infusion rate the additional N required could be more than accounted for by hepatic removal of free amino acids. At the higher rate of NH3 administration additional sources of N were apparently required to account fully for urea synthesis. Protein synthesis rates in the PDV and liver were unaffected by NH3 infusion but both whole-body (P < 0.05) and splanchnic tissue leucine oxidation were elevated at the higher rate of administration. Substantial synthesis of [15N]glutamine occurred across the liver, particularly with the greater NH3 supply, and enrichments exceeded considerably those of glutamate. The [15N]urea synthesized was predominantly as the single labelled, i.e. [14N15N], species. These various kinetic data are compatible with the action of ovine hepatic glutamate dehydrogenase (EC 1.4.1.2) in periportal hepatocytes in the direction favouring glutamate deamination. Glutamate synthesis and uptake is probably confined to the perivenous cells which do not synthesize urea.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1995

The importance of dietary polyamines in cell regeneration and growth.

The polyamines putrescine, spermidine and spermine are essential for cell renewal and, therefore, are needed to keep the body healthy. It was previously believed that polyamines are synthesized by every cell in the body when required. However, in the present paper evidence is provided to show that, as in the case of the essential amino acids, the diet can supply sufficient amounts of polyamines to support cell renewal and growth. Systematic analysis of different foods was carried out and from the data obtained, the average daily polyamine consumption of British adults was calculated to be in the range 350-500 mumol/person per d. The major sources of putrescine were fruit, cheese and non-green vegetables. All foods contributed similar amounts of spermidine to the diet, although levels were generally higher in green vegetables. Meat was the richest source of spermine. However, only a part of the polyamines supplied by the diet is available for use by the body. Based on experiments with rats it was established that polyamines were readily taken up from the gut lumen, probably by passive diffusion, and were partly metabolized during the process of absorption. More than 80% of the putrescine was converted to other polyamines and non-polyamine metabolites, mostly to amino acids. The enzyme responsible for controlling the bioavailability of putrescine was diamine oxidase (EC 1.4.3.6). For spermidine and spermine, however, about 70-80% of the intragastrically intubated dose remained in the original form. Considering the limitations on bioavailability (metabolism and conversion), the amounts of polyamines supplied by the average daily diet in Britain should satisfy metabolic requirements.

Adult↗