Leucine plasma concentration

The pharmacological effect of L-dopa is affected by diet (362). The off period in Parkinsonian patients treated with L-dopa is a clinical problem, since the efficacy of the drug suddenly fails. Because of the inverse relationship between the plasma levels of large neutral amino acid (LNAA) and the clinical performance of Parkinsonian patients (362) and the fact that the transcellular transport of L-leucine is inhibited by L-dopa (363) across primary cultured bovine brain capillary endothelial cells, the off period may be attributed to the membrane transport of L-dopa via LNAAT at the BBB. In addition to L-dopa, baclofen and melphalan are suggested to be taken up into the brain via amino acid transporter (363,364), and thereby, their brain transport might be also affected by the plasma concentration of large neutral amino acids. 

Absorption and metabolism The drug is absorbed rapidly from the small intestine (when empty of food). Levodopa has an extremely short half-life (1 to 2 hours), which causes fluctuations in plasma concentration. This may produce fluctuations in motor response ( on-off phenomenon), which may cause the patient to suddenly lose normal mobility and experience tremors, cramps, and immobility. Ingestion of meals, particularly if high in protein content, interferes with the transport of levodopa into the CNS. Large, neutral amino acids (for example, leucine and isoleucine) compete with levodopa for absorption from the gut and for transport across the blood-brain barrier. Thus levodopa should be taken on an empty stomach, typically 45 minutes before a meal. Withdrawal from the drug must be gradual. 

L-Dopa is not bound to plasma proteins. It crosses the blood-brain barrier by stereospeciflc saturable facilitated diffusion and competes with LNAA for transport into the brain. High-dose infusions of phenylalanine and leucine decrease the clinical response to L-dopa without altering L-dopa plasma concentrations. This has led to... 

Because the hver metabohzes the aromatic amino acids (i.e., phenylalanine, tyrosine, and tryptophan), methionine, and glutamine, the plasma concentrations of these amino acids are elevated in cirrhotic patients. Plasma concentrations of the branched-chain amino acids (BCAAs) (i.e., valine, leucine, and isoleucine) often are depressed because these amino acids are metabohzed by skeletal muscle. This altered plasma aminogram contributes to the development of hepatic encephalopathy. 

The neutral amino acids alanine, serine, threonine, asparagine, glutamine, valine, leucine, isoleucine, phenylalanine, tyrosine, tryptophan, histidine and citrulline share a common transporter at the luminal border of the epithelial cells in the renal tubuli and the epithelial cells in the small intestine [16]. In Hartnup disorder an impairment of this transporter leads to hyperexcretion of these neutral amino acids and to intestinal malabsorption. Excretion of tryptophan metabolites kynurenine and N-methyl-nico-tinamide is reduced. Plasma concentrations of the affected amino acids may be low normal or reduced. The inheritance is autosomal recessive. The hph2-deficient mouse has been postulated as a model for Hartnup disorder [17]. Affected persons may be asymptomatic, while some demonstrate pellagra-like photodermatitis or cerebellar ataxia due to a nicotinamide deficiency and respond well to the administration of nicotinamide [16]. 

Extrapolating from leucine turnover studies in pigs, it is estimated that endogenous HMB production is equal to 0.2 to 0.4 g of HMB/day in a 70-kg man, depending on leucine intake. Furthramore, turnover of HMB is thought to be relatively rapid, as basal plasma concentrations in normal humans range from 1 to 4 Plasma levels of... 

Plasma and urine samples from atherosclerotic and control rats were comparatively analyzed by ultrafast liquid chromatography coupled with ion trap-time-of-flight (IT-TOF) MS (UFLC-IT/TOF-MS) (16). They identified 12 metabolites in rat plasma and 8 metabolites in rat urine as potential biomarkers. Concentrations of leucine, phenylalanine, tryptophan, acetylcar-nitine, butyrylcamitine, propionylcamitine, and spermine in plasma and 3-0-methyl-dopa, ethyl /V2-acety I -1. -argininate, leucylproline, glucuronate, A(6)-(A-threonylcarbonyl)-adenosine, and methyl-hippuric acid in urine were decreased in atherosclerosis rats ursodeoxycholic acid, chenodeoxycholic acid, LPC (06 0), LPC (08 0), and LPC (08 1) in plasma and hippuric acid in urine were increased in atherosclerosis rats. The altered metabolites demonstrated abnormal metabolism of phenylalanine, tryptophan, bile acids, and amino acids. Lysophosphatidylcholine (LPC) plays an important role in inflammation and cell proliferation, which shows a relationship between LPC in the progress of atherosclerosis and other inflammatory diseases. 

An altered plasma amino acid pattern is observed in patients with liver cirrhosis and hepatic encephalopathy low concentrations of the branched-chain amino acids (leucine, valine, and isoleucine) and high levels of... 

Jorgensen and Majumdar125 reported that a single tube-feeding of L-tryp-tophan to well-fed adrenalectomized rats stimulated in vivo incorporation of [3H] leucine into brain proteins as well as liver proteins. Also, Nakhla and Majumdar126 reported that tube-feeding tryptophan to well-fed adrenalectomized rats induced an increase in the activity of cerebral acetylcholinesterase, which could be prevented when the animals were pretreated with actinomycin D. Whether or not the enhanced protein synthesis in the brain following tryptophan administration may be related to a rise in brain serotonin level caused by increased plasma tryptophan concentration is not known. 

An internal standard should always be used for every analysis carried out. Such an internal standard is an amino acid which is known to be absent from the sample under investigation. For instance, in blood plasma analysis a known amount of either of the non-physiological amino acids, nor leucine or a-amino-P-guanidinobutyric acid can be used. From the known amount of internal standard, the concentration of the unknown amino acid can be determined using peak area relationships, the difference in colour values for the unknown and the internal standard having been duly taken care of while doing calculations. 

The goal of therapy is to maintain plasma leucine concentrations of 100-200 pmoI/L for infants and children <5 years and 100-300 [tmol/L for those over 5 years of age. 

Determine the estimated increase or decrease in leucine, isoleucine, and valine intake that will be needed to improve the blood concentrations. Changes in 10 % increments are typical but can be higher or lower based on plasma amino acid concentrations [7]. 

Box 16.7 Considerations if Plasma Leucine Concentrations Are Elevated (Without Signs of Illness or Stress)... 

Eight (8) day-old infant weighing 4 kg diagnosed with MSUD through newborn screening. This patient presents asymptomatically. Recent labs show plasma leucine concentration is 600 pmol/L, isoleucine is 80 pmol/L and valine is 180 pmol/L. The infant is currently taking 23 oz of Enfamil Premium powdered formula... 

Plasma amino acid concentrations were monitored one to two times per week. Goals for the pregnancy included maintaining leucine and isoleucine concentrations between 100 and 300 tmol/L and valine concentrations between 200 and 400 pmol/L. Prealbumin, albumin, and... 

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