Branch-chained amino acids function

There are several commercially available sulfonylurea herbicides that contain a 2-pyrimidine group <2006H(68)561>. These compounds, which function by inhibition of acetolactate synthase (ALS), an enzyme involved in the early stage of branched-chain amino acid synthesis, include sulfometuron-methyl 1095, primisulfuron-methyl 1096, chlorimuron-ethyl 1097, bensulfuron-methyl 1098, ethoxysulfuron 1099, nicosulfuron 1100, and pyrazosulfuron-ethyl 1101. Related nonsulfonylureas include the sulfide pyrftalid 1102 and the ether pyriminobac-methyl 1103. 

Femstrom, J.D. (2005). Branched-chain amino acids and brain function. Journal of Nutrition, 135, 1539S-1546S. 

Proteasomes of Thermoplasma contain a single type of p subunit but eukaryotic proteasomes contain subunits with at least three distinct substrate preferences.347 M9c They all appear to use the same hydrolytic mechanism but in their substrate specificities they are chymotrypsin-like, peptidylglutamyl-peptide hydrolyzing, branched chain amino acid preferring, and small neutral amino acid preferring based on the P, amino acid residue. In the spleen some of the P subunits of the proteasomes appear to have been replaced by proteins encoded by the major histocompatibility complex of the immune system (Chapter 31).347 This may alter the properties of the proteasome to favor their function in antigen processing. Proteasomes are also ATP- and ubiquitin-dependent, as discussed in Section 6. 

Deficiency hypothesis Substances which are essential to the smooth functioning of the central nervous system are not provided, or are only inadequately provided, by a seriously damaged liver. This hypothesis relates to the branched-chain amino acids as well as cellular deficits of zinc, potassium, magnesium and unsaturated fatty acids. 

The protein and amino-acid metabolism of the liver is characterized by three essential functions (1.) production and breakdown of proteins, (2.) production and breakdown of amino acids as well as regulation of their concentrations in the blood, and (i.) detoxification of ammonium via the synthesis of urea (= excretory form) and glutamine (= non-toxic transport or storage form) with simultaneous regulation of the acid-base balance. The breakdown of branched-chain amino acids occurs only in the musculature by way of deamination, (s. pp 38, 43)... 

Nakamura, L, Ochiai, K., Imawari, M. Phagocytic function of neutrophils of patients with decompensated cirrhosis is restored by oral supplementation of branched-chain amino acids. Hepatol. Res. 2004 29 207-211... 

In the second approach, herbicide-resistance mutations in the Arabidopsis ALS gene were studied in E. coli. To do this, wild type and mutant Arabidopsis genes were functionally expressed in E. coli, such that the plant genes complemented a branched chain amino acid auxotrophy in the bacteria (Smith et al. 1989, PNAS in press). ALS enzyme assays on extracts prepared from E. coli expressing the mutant Arabidopsis gene indicated that the mutant enzyme is resistant to sulfonylurea herbicides but is sensitive to the imidazolinone herbicide imazaquin. This selective... 

In addition to the four acyl-CoA dehydrogenases involved in fatty acid oxidation, three acyl-CoA dehydrogenases specific for metabolites of branched-chain amino acids have been characterized, niey are isovaleryl-CoA dehydrogenase, 2-methyl-branched-chain acyl-CoA dehydrogenase, and isobutyryl-CoA dehydrogenase, which may also function in the P-oxidation of branched-chain carboxylic acids. 

The main function of vitamin B12 is thought to be in the metabolism of amino acids. Thus, B,2 is involved in the conversion of homocysteine to methionine and in the catabolism of some branched-chain amino acids. The neurological disorder that is usually associated with vitamin B12 deficiency is due to progressive demyelination of nervous tissue, thought to be owing to a build up of the vitamin Bj2 substrate, methylmalonyl CoA. This probably interferes with the formation of the myelin sheath. 

Inhibitors of Acetolactate Synthase (ALS/AHAS) The enzyme acetolactate synthase (ALS) plays in plants an essential role in branched-chain amino acid biosynthesis. In the pathway leading to valine and leucine, ALS catalyzes the formation of 2-acetolactate from two pyruvate molecules, and in the pathway to isoleucine the formation of 2-acetohydroxybutyrate from 2-ketobutyrate and pyruvate. Due to this double function the enzyme is also called with a more general term aceto-hydroxyacid synthase. ALS is inhibited by several groups of herbicides, mainly the sulfonylureas (SUs), imidazolinones (IMIs), triazolopyrimidines (TPs), pyrimidinylthiobenzoates(PTBs) and sulfonylaminocarbonyltriazolinone (SCTs) (see Chapter 2.1, M. E. Thompson). 

An alternative approach to estimating the metabolic capabilities of chloroplasts entails measurement of the light-dependent metabolism of radioactive tracers. Using isolated pea chloroplasts. Mills and Wilson (1978a) found that lysine, methionine, threonine, and isoleucine were synthesized from [ C]aspartate. Further evidence that aspartate was being metabolized via the anticipated pathways was provided by the demonstration that the synthesis of homoserine was inhibited by lysine and threonine (Lea et al., 1979). These results, combined with those relating to enzyme localization, lead to the concept that chloroplasts contain a complete functional sequence of enzymes which can facilitate the synthesis of the aspartate family and at least some of the branched-chain amino acids. This is consistent with the importance of chloroplasts in ammonia assimilation (Miflin and Lea, this volume. Chapter 4) and with the evidence that protein can be synthesized from CO2 in isolated plastids (Shepard and Leven, 1972 Huberer al., 1977). The actual fraction of [ ]02 which is utilized for amino acid biosynthesis in isolated plastids is usually quite small. Thus, reactions which normally occur outside of chloroplasts are considered to be of major importance in the synthesis of carbon skeletons such as oxaloacetate or pyruvate (Kirk and Leech, 1972 Leech and Murphy, 1976). 

The sequences of biochemical transformations involved in the synthesis of the aspartate family and branched-chain amino acids in multicellular plants are similar to those that occur in microorganisms. Support for this conclusion has been derived principally from isolation of a number of the requisite enzymes. Information on the kinetic and physical properties of enzymes is best achieved after extensive purification. In contrast, useful predictions of the physiological function of regulatory enzymes depend upon effective enzyme extraction and complete preservation of native properties. Since the latter objective has been emphasized during most investigations of enzymes associated with amino acid biosynthesis in plants, the bulk of our knowledge has been obtained from comparatively crude enzyme preparations. Results of both direct and competitive labeling experiments have added demonstrations of many of the predicted precursor-product relationships and a few metabolic intermediates have been isolated from plants. The nature of a number of intermediate reactions does, however, remain to be clarified notably, the reactions associated with the conversion of dihydropicolinate to lysine and those involved in the synthesis of leucine from 2-oxoisovalerate. 

Propionic acid fermentation is not limited to propionibacteria it functions in vertebrates, in many species of arthropods, in some invertebrates imder anaerobic conditions (Halanker and Blomquist, 1989). In eukaryotes the propionic acid fermentation operates in reverse, providing a pathway for the catabolism of propionate formed via p-oxidation of odd-numbered fatty acids, by degradation of branched-chain amino acids (valine, isoleucine) and also produced from the carbon backbones of methionine, threonine, thymine and cholesterol (Rosenberg, 1983). The key reaction of propionic acid fermentation is the transformation of L-methylmalonyl-CoA(b) to succinyl-CoA, which requires coenzyme B12 (AdoCbl). In humans vitamin B deficit provokes a disease called pernicious anemia. 

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