Dean W. Andersen

Metabolism of aspartame and its l-phenylalanine methyl ester decomposition product by the porcine gut☆

The intestinal metabolism of aspartame (N-L-alpha-aspartyl-L-phenylalanine methyl ester; APM) and its L-phenylalanine methyl ester (PME) decomposition product was evaluated in six young pigs. Equimolar doses (2.5 mmol/kg body weight) of APM, PME, and L-phenylalanine (PHE) administered to the proximal jejunum produced similar increases in portal blood PHE concentrations. Methanol, nondetectable in portal blood after PHE ingestion, increased markedly after administration of either APM or PME. Portal blood aspartate concentrations were unchanged after PME and PHE administration, but increased significantly after APM administration. Increases in portal blood PHE concentrations were significantly greater than were increases in aspartate concentrations following APM administration. Neither APM, PME, nor aspartyl-phenylalanine (AspPhe) were detected in portal or vena caval blood following administration of any test compound. Steady-state perfusion of the small intestine with APM showed a net intraluminal appearance rate of AspPhe at 36% of the disappearance rate of APM. During steady-state PME perfusion, PHE had a significantly greater net appearance rate than during APM perfusion. Methanol appearance rates were slightly, but not significantly, higher during PME than during APM perfusions. The data suggest that (1) APM is hydrolyzed to AspPhe and both APM and PME are hydrolyzed to their constituent amino acids and and methanol prior to entering the portal circulation; (2) AspPhe is an important intraluminal intermediate in aspartame metabolism; and (3) aspartate is rapidly metabolized by the enterocyte.

Urinary Excretion of Endogenous Hydroxyproline by Normal Male Infants

Extract: Rates of urinary excretion of total hydroxyproline by 38 normal fullsize male infants were determined on 176 occasions. Each urine collection period was 72 hours. When the period of urine collection was begun between the fourth and eighth day of life, mean rate of excretion was 30.6 mg/day (standard deviation 6.9 mg/day). Maximal rates of urinary excretion were observed between 21 and 60 days of age (mean: 48.1 mg/day; standard deviation 9.7 mg/day). Between 121 and 582 days of age, mean rate of excretion had decreased slightly to 43 mg/day.Eleven infants were each studied on at least five occasions between 20 and 120 days of age. Mean rate of urinary excretion of hydroxyproline by each infant was shown to be significantly correlated with rate of gain in length but not with rate of change in weight or surface area.Speculation: During normal infancy it seems probable that a major proportion of the hydroxyproline excreted in the urine is derived from collagen of bone. Rate of excretion probably parallels rate of bone growth. Thus, any disorder that depresses the normal rate of linear growth is likely to result in sharp diminution of urinary excretion of hydroxyproline. Such a biochemical index of growth may be clinically useful.

Intravenous Lipid Emulsions in the Treatment of Essential Fatty Acid Deficiency: Studies in Young Pigs

ABSTRACT: Essential fatty acid deficiency (EFAD) occurs in infants fed fat-free mixtures of glucose and amino acids. Although infusion of lipid emulsion rapidly reverses clinical symptoms, little is known about effects on tissue fatty acids. To study this question, five groups (n = 4/group) of neonatal pigs were studied. Three groups (I, II, and V) were made EFAD by feeding diets without essential fatty acids (EFA) for days 5 to 33 of life. Groups III and IV were fed a control diet. By 33 days, animals fed the deficient diet showed clinical symptoms and biochemical signs of EFAD. On days 33 to 54 of life, group I animals were fed the EFA-deficient diet and infused with lipid emulsion, providing 3.6% of energy as linoleic acid; group II animals were fed the deficient diet and infused with linoleic acid at 7.2% of energy; group V animals were fed the deficient diet with no lipid emulsion; group III and IV animals were fed the EFA-deficient diet and provided EFA intravenously. Infusion of lipid emulsion rapidly reversed clinical symptoms of EFAD and returned plasma phospholipid ω6 fatty acids levels to normal. However, erythrocyte and liver phospholipid ω6 fatty acid content and adipose tissue reserves of ω6 fatty acids normalized more slowly. Three weeks of infusion of linoleic acid at 3.6% of energy and 2 weeks of infusion at 7.2% of energy were required to return erythrocyte phospholipid fatty acids to normal. Liver phospholipid fatty acid composition still showed biochemical evidence of EFAD in animals treated with linoleic acid at 3.6% of energy for 3 wk. Adipose tissue reserves of ω6 fatty acids did not return to normal in animals treated for 3 wk with linoleic acid at 3.6% of energy. Two to 3 wk of treatment with linoleic acid at 7.2% of energy was required to return adipose tissue 6ω fatty acids reserves to normal.

Effect of meal components on peripheral and portal plasma glutamate levels in young pigs administered large doses of monosodium-L-glutamate☆

Mean peak plasma glutamate concentrations and area under the plasma glutamate concentration-time curve are much lower in adult humans ingesting monosodium L-glutamate (MSG) in formula than in water. The present study investigated the effects of individual meal components on portal and vena caval plasma glutamate concentration in young pigs administered MSG. Portal vein catheters and gastrojejunal tubes were placed in four young male pigs, and the animals were allowed to recover. Each animal was then administered four water solutions providing 500 mg/kg body weight MSG in a Latin square design. One solution provided only MSG; the second provided MSG and 1 g/kg body weight metabolizable carbohydrate (partially hydrolyzed corn starch); the third provided MSG and 1 g/kg body weight nonmetabolizable carbohydrate (beta-cellobiose); and the fourth provided MSG and 0.4 g/kg body weight of an amino acid mixture (Aminosyn, Abbott Laboratories, North Chicago, Ill). Mean peak plasma glutamate concentration and area under the plasma glutamate concentration-time curve were significantly lower (P less than 0.05) in both portal and vena caval blood when MSG was administered with metabolizable carbohydrate than when administered in water. Simultaneous ingestion of MSG with nonmetabolizable carbohydrate (beta-cellobiose) or amino acids had no significant effect on either mean peak portal or vena caval plasma glutamate concentration or area under the plasma glutamate concentration-time curves when compared to values observed when MSG was administered alone. The data suggest that metabolizable carbohydrate is the meal component affecting plasma glutamate concentration.

Effect of waxy corn starch modification on growth, serum biochemical values and body composition of pitman-moore miniature pigs

Abstract Four groups each of eight Pitman-Moore miniature pigs were weaned at 3 days of age and then fed for 25 days on formula diets identical except for the type of carbohydrate. The diets contained thin-boiling waxy corn starch or one of three chemical modifications of this starch (phosphated distarch phosphate, distarch phosphate and hydroxypropylated distarch glycerol). No statistically significant treatment-related effects were observed on growth, biochemical values of blood or serum, or carcass or liver composition.

Effects of age, sex, and diet upon carcass and liver fatty acid composition of Pitman-Moore miniature pigs

Fatty acid composition of carcass and liver and proximate analysis of liver were studied in 14–28 day old Pitman-Moore miniature pigs, 26 sow-reared and 30 fed a semisynthetic diet in which the fat was lard. With increasing age, fat of carcass, but not of liver, became significantly more unsaturated. The percentage of palmitic acid (16∶0) and total saturated fatty acids was significantly greater and the percentage of linoleic acid (18∶2) and total unsaturated fatty acids significantly less in carcasses of male than of female pigs. No sex-related differences in proximate or fatty acid composition of the liver were noted. Carcasses of sow-reared pigs contained significantly greater percentages of myristic (14∶0), palmitoleic (16∶1), and linoleic acids and significantly lesser percentages of stearic (18∶0) and oleic (18∶1) acids than did those of pigs fed the semisynthetic diet. Diet-related differences in fatty acid composition of liver closely paralleled those of carcass, although liver contained markedly greater percentages of stearic and arachidonic (20∶4) acids and lesser percentages of palmitoleic and oleic acids than did carcass. Diet-related differences in fatty acid composition of carcass and liver are discussed in relation to the fatty acid composition of dietary fat (sow milk and lard).

Utilization of parenterally administered glucose oligosaccharides when infused with glucose and amino acids in postsurgical patients

Utilization of intravenously administered oligosaccharides was tested in postsurgical patients by infusing them simultaneously with glucose and amino acids. Thirty two patients were infused with one of two parenteral regimens for four-day periods. Twenty-two patients received a nutritional regimen providing 46 g glucose, 32.5 g amino acids, and 45 g oligosaccharides per liter, while the remaining ten patients received the same solution without oligosaccharides. Patients infused with the test solution received an overall four-day mean +/- SD of 106 +/- 24.2 g oligosaccharide per day. The mean overall four-day excretion of total glucose (free plus oligosaccharide bound) was significantly higher (P less than 0.001) in patients infused with oligosaccharides (46.1 +/- 29.0 g/d) than in reference patients (1.19 +/- 1.20 g/d). Of the total carbohydrate excreted in patients receiving oligosaccharides, 11.3 +/- 13.1 g/d were glucose, 14.8 +/- 13.1 g/d were maltose plus maltotriose, and 20.8 +/- 19.3 g/d were oligosaccharides of maltotetraose size or larger. Although overall utilization of infused oligosaccharide for all patients was only 58.5% +/- 23.1%, three of the patients showed unexpectedly good utilization (94.6% +/- 1.24%).

Digestibility of acetylated distarch glycerol—effect on growth, serum biochemical values and body composition of Pitman-Moore miniature pigs

Abstract Two groups each of eight Pitman-Moore miniature pigs were weaned at 3 days of age and then, for 25 days, were allowed unrestricted access to formula diets identical except for the type of carbohydrate. The diets contained 6% of thin-boiling waxy corn starch or acetylated distarch glycerol. At 14 and 21 days of age, the body weight of pigs fed the control starch diet was significantly higher, while at 28 days, the weight of the empty caecum and the water content of the wet carcass and fat-free wet liver were significantly lower and the carcass-fat and liver-protein contents were significantly greater than the corresponding values for pigs fed the diet containing acetylated distarch glycerol as the sole carbohydrate.

Source of the urinary maltose and maltotriose excreted during intravenous infusion of oligosaccharide solutions in young pigs

Pigs infused with preparations of glucose oligosaccharides excrete sizeable quantities of maltose in urine despite the absence of maltose in the infused solution. Maltose infused without other oligosaccharides is well utilized. Our studies examined possible sources of excreted maltose. We first examined whether simultaneous infusion of larger oligosaccharides with maltose inhibits maltose utilization. Four young pigs were infused for four days with 20 g/d of a maltose-free oligosaccharide preparation to which tracer quantities of U-14C-maltose were added. Urinary excretion of maltose-plus-maltotriose increased significantly (P less than .05) from a mean +/- SD baseline value of .01 +/- .01 g/d to an overall four-day mean value of 1.33 +/- 0.47 g/d. However, only 10.7 +/- 0.78% of infused 14C-maltose was excreted, indicating that simultaneous infusion of larger oligosaccharides did not inhibit maltose utilization. The second study examined whether maltotriose present in the oligosaccharide mixture was the source of excreted maltose. Four young pigs were infused for three days with 20 g/d of a special preparation of oligosaccharides containing only trace quantities of maltose and maltotriose. Urinary maltose plus maltotriose excretion increased significantly (P less than .05) from a mean +/- SD baseline value of .01 +/- .01 g/d to 1.65 +/- 0.41 g/d during oligosaccharide infusion. The data suggest that excreted maltose and maltotriose arise from the catabolism of larger oligosaccharides.

Method For Evaluating Utilization of Infused Oligosaccharides in Postsurgical Patients

Oligosaccharides are potential sources of carbohydrate-derived energy for use in parenteral nutrition regimens. Clinical studies indicate that although some patients utilize infused oligosaccharides well, many patients do not. These results suggest that oligosaccharides might be useful as a parenteral energy source for selected patients. This report describes a method, suitable for use by nursing staff on the ward, to determine oligosaccharide utilization and identify patients utilizing oligosaccharides well. Oligosaccharides excreted in urine are hydrolyzed enymatically to glucose using alpha-glucosidase and alpha-amylase, and the glucose released is measured by a test tape method. The results obtained agree well with the acid hydrolysis-spectrophotometric assay for oligosaccharide excretion used in earlier studies. The method readily identified postsurgical patients utilizing infused oligosaccharides poorly in both prospective and retrospective studies.