Plasma valine

As the name implies, the odor of urine in maple syrup urine disease (brancbed-chain ketonuria) suggests maple symp or burnt sugar. The biochemical defect involves the a-keto acid decarboxylase complex (reaction 2, Figure 30-19). Plasma and urinary levels of leucine, isoleucine, valine, a-keto acids, and a-hydroxy acids (reduced a-keto acids) are elevated. The mechanism of toxicity is unknown. Early diagnosis, especially prior to 1 week of age, employs enzymatic analysis. Prompt replacement of dietary protein by an amino acid mixture that lacks leucine, isoleucine, and valine averts brain damage and early mortality. 

Similar to the work described by Spohn et al. [34], a trienzyme sensor was developed recently for the determination of branched-chain amino acids (L-valine, L-leucine, and L-isoleucine). Leucine dehydrogenase, NADH oxidase, and peroxidase were coimmobilized covalently on tresylate-hydrophylic vinyl polymer beads and packed into a transparent PILL tube (20 cm X 1.0 id), which was used as flow cell. The sensor was free of interferences from protein and NH4+ and it was stable for 2 weeks. The sensor system was applied to the determination of branched-chain amino acids in plasma with recoveries ranging from 98 to 100% [36],... 

For example, alkaponuria is characterized by homogentisic acid in urine phenylketonuria, which results in mental retardation, is characterized by quantities of phenylpyruvic acid in the urine. It is diagnosed in a suspected patient by determining the amount of this acid in the urine and the increased levels of phenylalanine in the plasma. Maple sugar disease is diagnosed the presence of large amounts of the branched chain amino acids, such as valine, leucine, and isoleucine in the blood and urine. 

Human plasma NSTEACS 45 GC-MS Citric acid J. 4-Hydroxyproline J, Aspartic acid J, Fructose J, Lactate t Urea t Glucose t Valine t (11)... 

Human plasma Diabetes 2422 LC-MS/MS Isoleucine Leucine Valine Tyrosine Phenylalanine (26)... 

Other close structural analogues of saquinavir (17) incorporating the hydroxyethylamine isostere have been developed to provide potent inhibitors of HIV-1 protease. For example, palinavir (21) (Table III) inhibits the enzyme with a Kj of 0.03 nM and blocks viral replication with an EC50 of 7 nM This antiviral potency was not substantially affected by the addition of oci-acid glycoprotein at physiological concentrations however, 21 did show reduced activity against HIV-1 variants with active site mutations, including valine-32 to isoleucine and isoleucine-84 to valine (Lamarre et al., 1997). Pharmacokinetics in rats have been reported for palinavir. The compound exhibited an oral bioavailability of 20 to 30%, with a plasma half-life of 30 to 50 minutes. 

The liver plays a central role in the synthesis of nearly all circulating proteins. Plasma contains 60-80 g/L of protein and this is turned over at a rate of approximately 250 g/day. A variety of proteins are constructed in the liver using amino acids (Aa) as their basic building blocks. Amino acids are categorised as essential and non-essential , the former being a requirement of dietary intake as they cannot be constructed in vivo, whereas the latter can be synthesised hepatically. The essential amino acids are further categorised as branched-chain amino acids (BCAA leucine, valine, isoleucine) or aromatic amino acids (AAA phenylalanine, tyrosine, methionine) according to their structure. Table... 

Breakdown of isoleucine, valine, threonine, and methionine results in the production of propionyl-CoA. Propionyl-CoA, in turn, is catabolized to succinyl-CoA via the intermediate methylmalonyl-CoA. Methylmalonyl-CoA is a compoimd of imusual interest to nutritional scientists. This compound accumulates in the cell during a vitamin B12 deficiency. Vitamin B12 deficiency is not a rare disease, as it appears in a common autoimmune disease called pernicious anemia. Vitamin B12 deficiency also occurs in strict vegetarians who avoid meat, fish, poultry, and dairy products. Methylmalonyl-CoA can also build up with rare genetic diseases that involve the production of defective, mutant forms of methylmalonyl-CoAmutase. Most of the methylmalonyl-CoAthat accumulates to abnormally high levels in the cell is hydrolyzed to methylmalonic acid (MMA), which leaves the cell for the bloodstream and eventual excretion in the urine. Some of the MMA is converted back to propionyl-CoA, resulting in the production and accumulation of propionic acid in the cell. The measurement of plasma and urinary MMA has proven to be a method of choice for the diagnosis of vitamin B12 deficiency, whether induced by pernicious anemia or by dietary deficiency. 

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