Infusion Of Essential Amino Acids Research Articles

Effects of Amount and Profile of Amino Acids Supply on Lactation Performance, Mammary Gland Metabolism, and Nitrogen Efficiency in Holstein Dairy Cows.

To evaluate the effects of amount and profile of amino acid (AA) on milk protein yield (MPY), mammary metabolism, and efficiency of nitrogen use (ENU), ten cows were used in 5 × 5 replicated Latin squares and fed a positive control (16.1% crude protein-CP) or two lower CP diets (14.6 and 13.2%) with or without essential AA (EAA) infusion. The EAA solutions provided predicted limiting EAA in each treatment and were continuously infused into the abomasum of the cows. Milk production and MPY were not affected by treatment (mean 35.4 kg/d and 1.03 kg/d, respectively). Efficiency of nitrogen utilization was increased as dietary CP decreased but was not affected by EAA infusion (p < 0.01). Energy-corrected milk production was increased by EAA infusion into 13.2% CP, but not into 14.6% CP diet (p = 0.09), reaching the positive control value. Infusions increased mammary affinity for non-infused EAA (Ile, Phe, Thr, and Trp), allowing the same MPY despite lower arterial concentrations of these AA. Higher arterial concentrations of infused EAA did not increase their mammary uptake and MPY (p = 0.40; p = 0.85). Mammary metabolism did not fully explain changes in N efficiency, suggesting that it might be driven by less extramammary catabolism as AA supply was reduced.

Glucose supplementation stimulates peripheral branched-chain amino acid catabolism in lactating dairy cows during essential amino acid infusions

To determine how glucose modulates protein synthesis when essential AA are in abundant supply, 5 early-lactation, rumen-fistulated Holstein dairy cows were fed a diet containing 6.95 MJ/kg of net energy for lactation and 12.4% crude protein and abomasally infused for 5d with saline, 844 or 1,126g/d of a complete essential AA mix, with and without the inclusion of 1,000g/d of glucose, in a 5×5 Latin square design. Infusion of essential AA increased milk yield by 4.1kg/d, milk protein by 256g/d, milk fat by 95g/d, and milk urea nitrogen by 70% compared with saline, with no differences between the level of essential AA infusion. The addition of glucose to essential AA infusate did not stimulate milk protein yield or concentration, but reduced milk urea nitrogen by 17% and decreased milk fat yield. Arterial concentrations of total essential AA increased 3- to 4-fold, mammary clearance decreased 61%, and mammary uptake of essential AA increased 65% in response to essential AA infusion. Arterial branched-chain AA concentrations declined 29% in response to glucose and mammary clearance increased 48%, but mammary AA uptake was unchanged. Essential AA infusion increased plasma 3-methylhistidine by 50% and reduced muscle branched-chain α-keto acid dehydrogenase kinase abundance by 14%, indicating stimulation of muscle protein turnover and branched-chain AA catabolism, respectively. Glucose had no further effect on muscle branched-chain α-keto acid dehydrogenase kinase abundance but decreased mRNA expression of branched chain aminotransferase 1. Lack of further increases in plasma 3-methylhistidine or greater stimulation of muscle branched-chain AA catabolism indicates that muscle protein degradation was unchanged with glucose but that accretion may have been stimulated. The decrease in circulating branched-chain AA concentrations and nitrogen excretion in response to glucose suggests that surplus essential AA were redirected to peripheral, extra-mammary tissues.

Essential amino acid infusions stimulate mammary expression of eukaryotic initiation factor 2Bε but milk protein yield is not increased during an imbalance

Essential amino acid (EAA) deficiencies and imbalances were created in lactating cows by using an infusion subtraction protocol to explore effects on milk protein yield and activity state of regulators of mRNA translation in the mammary glands. Six lactating cows on a diet of 11.2% protein were infused abomasally for 5d with saline, 563g/d of a complete EAA mix, or EAA without His, Met, Phe, or Trp in a 6×6 Latin square design. Infusion of complete and imbalanced EAA solutions increased mammalian target of rapamycin (mTOR) signaling in the mammary glands, as evidenced by higher ribosomal S6 kinase 1 (S6K1) phosphorylation compared with saline infusion. Total S6K1 abundance was decreased by imbalanced AA infusions. Except for the mixture lacking Phe, infusion of EAA, whether imbalanced or not, increased abundance of total eukaryotic initiation factor 2Bε (eIF2Bε). A correlation of 0.33 between phosphorylation state of S6K1 and total eIF2Bε abundance suggests that an mTOR-mediated upregulation of eIF2Bε translation occurred. Despite increased mTOR/eIF2Bε signaling, milk protein yields increased only with the complete EAA mixture compared with saline. Low plasma concentrations of His, Met, and Phe during their respective imbalances likely interfered with protein synthesis. Total abundance and phosphorylation state of eukaryotic initiation factor 2α were not responsible for the interference. Further study of eIF2Bε as a regulator of milk protein yield is warranted.

Leucine acts in the brain to suppress food intake but does not function as a physiological signal of low dietary protein.

Intracerebroventricular injections of leucine are sufficient to suppress food intake, but it remains unclear whether brain leucine signaling represents a physiological signal of protein balance. We tested whether variations in dietary and circulating levels of leucine, or all three branched-chain amino acids (BCAAs), contribute to the detection of reduced dietary protein. Of the essential amino acids (EAAs) tested, only intracerebroventricular injection of leucine (10 μg) was sufficient to suppress food intake. Isocaloric low- (9% protein energy; LP) or normal- (18% protein energy) protein diets induced a divergence in food intake, with an increased consumption of LP beginning on day 2 and persisting throughout the study (P < 0.05). Circulating BCAA levels were reduced the day after LP diet exposure, but levels subsequently increased and normalized by day 4, despite persistent hyperphagia. Brain BCAA levels as measured by microdialysis on day 2 of diet exposure were reduced in LP rats, but this effect was most prominent postprandially. Despite these diet-induced changes in BCAA levels, reducing dietary leucine or total BCAAs independently from total protein was neither necessary nor sufficient to induce hyperphagia, while chronic infusion of EAAs into the brain of LP rats failed to consistently block LP-induced hyperphagia. Collectively, these data suggest that circulating BCAAs are transiently reduced by dietary protein restriction, but variations in dietary or brain BCAAs alone do not explain the hyperphagia induced by a low-protein diet.

Effect of prolonged intravenous glucose and essential amino acid infusion on nitrogen balance, muscle protein degradation and ubiquitin-conjugating enzyme gene expression in calves

BackgroundIntravenous infusions of glucose and amino acids increase both nitrogen balance and muscle accretion. We hypothesised that co-infusion of glucose (to stimulate insulin) and essential amino acids (EAA) would act additively to improve nitrogen balance by decreasing muscle protein degradation in association with alterations in muscle expression of components of the ubiquitin-proteasome proteolytic pathway.MethodsWe examined the effect of a 5 day intravenous infusions of saline, glucose, EAA and glucose + EAA, on urinary nitrogen excretion and muscle protein degradation. We carried out the study in 6 restrained calves since ruminants offer the advantage that muscle protein degradation can be assessed by excretion of 3 methyl-histidine and multiple muscle biopsies can be taken from the same animal. On the final day of infusion blood samples were taken for hormone and metabolite measurement and muscle biopsies for expression of ubiquitin, the 14-kDa E2 ubiquitin conjugating enzyme, and proteasome sub-units C2 and C8.ResultsOn day 5 of glucose infusion, plasma glucose, insulin and IGF-1 concentrations were increased while urea nitrogen excretion and myofibrillar protein degradation was decreased. Co-infusion of glucose + EAA prevented the loss of urinary nitrogen observed with EAA infusions alone and enhanced the increase in plasma IGF-1 concentration but there was no synergistic effect of glucose + EAA on the decrease in myofibrillar protein degradation. Muscle mRNA expression of the ubiquitin conjugating enzyme, 14-kDa E2 and proteasome sub-unit C2 were significantly decreased, after glucose but not amino acid infusions, and there was no further response to the combined infusions of glucose + EAA.ConclusionProlonged glucose infusion decreases myofibrillar protein degradation, prevents the excretion of infused EAA, and acts additively with EAA to increase plasma IGF-1 and improve net nitrogen balance. There was no evidence of synergistic effects between glucose + EAA infusion on muscle protein degradation or expression of components of the ubiquitin-proteasome proteolytic pathway.

Milk Protein Response to Abomasal or Mesenteric Vein Essential Amino Acid Infusion in Lactating Dairy Cows

Previous experiments performed at our location suggested that the milk protein response to infusions of mixed essential amino acids (EAA) was greater when these were supplied via intravenous rather than abomasal or duodenal routes. However, as far as we are aware there have been no direct comparisons of the milk protein response to site of EAA provision in the same animals. Our objective was to directly compare the milk protein responses when cows were given mixtures of EAA provided via abomasal or mesenteric vein infusions. Four multiparous, ruminally cannulated, multicatheterized Holstein × Friesian cows averaging 18 wk postpartum were fed dehydrated alfalfa, grass silage, and low protein (11.9% CP, DM basis) concentrates at 30, 20, and 50%, respectively, of dry matter (DM) offered. Total mixed rations (14% crude protein, DM basis) were fed daily as 3 equal meals at 8-h intervals and 95% of ad libitum DM intake. The experimental design was a single reversal with two 10-d infusion periods separated by a 10-d rest period. Each infusion period consisted of 4-d control infusions into the mesenteric vein (saline at 2 ml/min) and abomasum (water at 9 L/d) followed by 6-d infusion of a mixture of EAA equal to 400g of milk protein/d into the abomasum or mesenteric vein. Control infusions continued into the site not receiving EAA. Intake of DM (20.3 kg/d), milk yield (28.9 kg/d), and milk fat concentration (41.2 g/ kg) were not affected by EAA infusions. Milk protein concentration (33.4 vs 34.6 g/kg) and output (938 vs. 982 g/d) were increased and milk lactose concentration was decreased (46.6 vs. 46.1 g/kg) by EAA, but the responses were not affected by infusion site. Recovery of EAA as increased milk protein output (10.9%) was similar for intravascular and abomasally infused EAA in these cows, but these responses were low compared with published effects of postruminal casein infusion.

Glucose or essential amino acid infusions in late pregnant and early lactating Simmenthal cows failed to induce a leptin response.

To assess the leptin response to metabolic challenges, three Italian Simmental cows were infused for 6 h: with (a) saline (control); (b) glucose; and (c) amino acid solutions according to a 3 x 3 Latin square experiment. The infusions were carried out at the 36th week of pregnancy, and the second and 12th week of the following lactation. At each of the three infusion periods, blood samples were collected from the jugular vein before and 15, 30, 120, 180, 240, 300 and 360 min after the beginning of each infusion. All samples were analysed for leptin, insulin, glucagon, growth hormone (GH), glucose, non-esterified fatty acids (NEFA) and urea. The physiological phase of the cows significantly affected the basal concentrations of insulin, glucagon, urea and NEFA. The infusion of both glucose and the amino acid solutions did not affect leptin concentrations. Insulin response was significantly increased when animals were infused with the glucose solution and, within treatment, the greatest response was observed at the 12th week of lactation. The greatest glucagon response was observed when infusing the amino acid solution. Urea response to all treatments increased from the dry period to the 12th week of lactation. The GH and NEFA responses were not affected by treatments. The Multi Species radio-immunoassay used in this study showed a lower sensitivity for ruminant leptin which may partially explain the lack of significant leptin variations. However, it can be hypothesized that leptin variations around parturition can be affected by the negative energy balance, and leptin release is not acutely affected by glucose and amino acid availability. In addition, no short-term relationship were found between insulin, glucagon and GH and leptin release in Italian Simmental cows during the dry period and early lactation.

Effect of jugular vein essential amino acid infusion on milk production in dairy cattle

Milk protein concentration can be influenced by dietary manipulation, but the efficiency of amino acid transfer into milk and the predictability of the response are both poor. Previous reports from this research group have demonstrated that milk protein concentration can be repeatedly increased in response to vascular infusions of essential amino acids (EAA) in animals fed on a low crude protein (CP) diet (140 g CP/kg DM) in mid-lactation (Metcalf et al., 1996). The present study was designed to compare milk protein content responses to vascular EAA infusion in animals fed a high protein diet (180 g CP/kg DM) at peak lactation.

Effect of jugular vein essential amino acid infusion on milk production in dairy cattle

Milk protein concentration can be influenced by dietary manipulation, but the efficiency of amino acid transfer into milk and the predictability of the response are both poor. Previous reports from this research group have demonstrated that milk protein concentration can be repeatedly increased in response to vascular infusions of essential amino acids (EAA) in animals fed on a low crude protein (CP) diet (140 g CP/kg DM) in mid-lactation (Metcalf et al., 1996). The present study was designed to compare milk protein content responses to vascular EAA infusion in animals fed a high protein diet (180 g CP/kg DM) at peak lactation.

The Induction of Specific Dynamic Action in Channel Catfish by Infusion of Essential Amino Acids

Specific dynamic action (SDA) is defined as the increase in O₂ consumption following the ingestion of a meal. This phenomenon has been observed for many years but is still not well understood. It has been suggested, however, that the metabolic cost associated with growth is the prime causative agent of SDA. The purpose of this study was to determine whether SDA could be artificially induced in the channel catfish by infusing an amino acid mixture directly into the bloodstream. The infusion of an essential amino acid (EAA) mixture equivalent to that in the protein of a standard ration (40 g kg⁻¹) resulted in significant increases in O₂ consumption and ammonia excretion. Plasma amino acid concentrations increased in accordance with O₂ consumption and ammonia excretion rates. The infusion of a D-essential amino acid mixture did not cause a significant increase in O₂ consumption or ammonia excretion. The increase in metabolism following EAA infusion was therefore not due to osmotic or physiological stress. Th...

The Relationship between Specific Dynamic Action (SDA) and Protein Synthesis Rates in the Channel Catfish

The purpose of the study was to investigate the relationship between specific dynamic action (SDA) and the rate of protein synthesis following a simulated meal consisting of an essential amino acid infusion. After such an infusion, the O₂ consumption rates of catfish approximately doubled, and the rate of protein synthesis in white muscle rose from 1.3 to 2.86 mg g⁻¹ d⁻¹. After pretreatment with the protein synthesis inhibitor cycloheximide, there was no significant SDA (defined as the increase in oxygen consumption) and the rate of protein synthesis fell to 0.34 mg g⁻¹ d⁻¹. There was good agreement between the magnitude of the SDA observed, the magnitude of the increase in protein synthesis, and theoretical calculations of the expected metabolic costs of protein synthesis based on oxygen equivalents for ATP production and ATP requirements for protein formation. The results support the idea that SDA may be directly attributable to the cost of protein synthesis, and therefore to the metabolic cost of growth.

Effect of CCK-OP and intraduodenal administration of essential amino acids on intraluminal pressures of sigmoid and rectum in patients with Chagasic megacolon.

The motility of the sigmoid colon and rectum was studied by manometry in patients with Chagasic megacolon and in control individuals using two different experimental procedures: (1) intravenous infusion of saline, followed by intravenous infusion of cholecystokinin octapeptide (OP-CCK) at the dose of 20 ng/kg/hr; and (2) intraduodenal instillation of saline followed by a solution of essential amino acids at a flow of 10 ml/min. CCK-OP induced an increase in motility index in the sigmoid colon (P less than 0.05) and rectum (P less than 0.05) in the controls, whereas intraduodenal infusion of amino acids produced a significant increase in motility index exclusively in the sigmoid colon (P less than 0.005). A significant increase (P less than 0.05) in sigmoid colon motility also occurred in the control group after duodenal saline infusion was interrupted. The release of other substances in addition to CCK must have been responsible for the different behavior of sigmoid colon and rectum in response to the stimuli used. Neither procedure caused significant changes in the motility of the sigmoid colon or the rectum of the Chagasic patients. The extensive intramural denervation occurring in Chagasic megacolon probably destroys the neural pathway through which OP-CCK and the substances released by the duodenum by the infusion of essential amino acids activate the motor cells of the human terminal intestine.

腎不全用必須アミノ酸製剤投与時の血中有機酸のgas chromatography-mass spectrometry分析

腎不全用必須アミノ酸製剤投与時の血中有機酸のgas chromatography-mass spectrometry分析

Bile acid and pancreatic trypsin outputs are parallel during intraduodenal infusion of essential amino acids

There is disagreement as to whether contraction of the gallbladder occurs simultaneously with secretion of pancreatic enzymes during food ingestion. One study that employed exogenous cholecystokinin (CCK) alone showed dissociation of total bile acids (TBA) and trypsin outputs, while another study that employed exogenous CCK plus secretin showed parallel outputs of TBA and trypsin. Since previous studies have suggested that intraduodenal infusion of essential amino acids (EAA) evokes pancreaticobiliary secretion similar to that observed with food ingestion, we infused increasing doses of EAA intraduodenally in 10 subjects with intact gallbladder and in 10 subjects with previous cholecystectomy and measured total bile acids and trypsin outputs serially. In subjects with intact gallbladder, increasing molar doses of EAA induced parallel increases of TBA and trypsin outputs. In subjects with previous cholecystectomy trypsin outputs during infusion of EAA were similar to subjects with intact gallbladder, but their TBA outputs remained constant during the entire infusion period. Serial concentrations of plasma secretin did not change during intraduodenal infusion of EAA. These observations suggest that the gallbladder empties bile in concert with secretion of pancreatic enzymes following food ingestion.

Potential danger of intravenous infusion of essential amino acids

Potential danger of intravenous infusion of essential amino acids

Potential danger of intravenous infusion of essential amino acids

Potential danger of intravenous infusion of essential amino acids

Potential danger of intravenous infusion of essential amino acids

Potential danger of intravenous infusion of essential amino acids

Potential danger of intravenous infusion of essential amino acids

Potential danger of intravenous infusion of essential amino acids

Effects of increased supply of essential amino acids on the metabolism of the isolated perfused guinea-pig mammary gland

The effects of high rates of infusion of essential amino acids on amino acid uptake by the isolated perfused guinea-pig mammary gland were studied. Infusion of methionine, tyrosine, phenylalanine, histidine and tryptophan (designated group 1) resulted in significant increases in the uptakes of tyrosine, phenylalanine and histidine. Methionine, tryptophan and other essential amino acids were not significantly affected. Infusion of threonine, valine, isoleucine, leucine, lysine and arginine (designated group 2) resulted in significant increases in uptake of all these amino acids. Group 1 amino acid uptake was not significantly affected. Infusion of all the essential amino acids (i.e. groups 1 and 2 together) resulted in significant increases in all their uptakes. Using as index 'the predicted rate of protein synthesis', infusion of group 1 and 2 together led to an apparent 27% increase in protein synthesis. The above results are discussed in relation to the control of milk protein synthesis by limiting essential amino acids.

Factors affecting delivery of bile to the duodenum in man

Studies utilizing balloon-occludable T or duodenal tubes in subjects with and without gallbladders were undertaken to identify the contribution of the gallbladder, the sphincter of Oddi, and bile salts to the delivery of bile to the duodenum. Patients with and without a functional sphincter of Oddi and with and without a gallbladder were compared. The presence of a functional sphincter of Oddi in duodenal tube patients reduced bile salt output by more than 67% from that observed in T-tube patients. When cholecystectomized and normal patients were compared using the duodenal tube, peak bile salt output was significantly increased in normal subjects, reflecting gallbladder contraction, but total bile salt output was not significantly increased, suggesting that the gallbladder has a minor role in bile delivery. Exogenous infusion of cholecystokinin produced much more stable bile secretion than did endogenous release of cholecystokinin by intraduodenal infusion of essential amino acids. This rhythmic release of bile after endogenous cholecystokinin release was related to the concentration of bile salts in the intestinal lumen. Thus, delivery of bile to the duodenum is wave-like and is predominantly controlled by the sphincter of Oddi.