Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0271742 (AAA)
 3,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The sequential changes in plasma free amino acid concentration were analyzed and compared in burned patients with sepsis (n = 12) and without sepsis (n = 19). After burn injury, phenylalanine, methionine, lysine, and the Phe/Tyr ratio were significantly increased in two groups (P < 0.05-0.01). Threonine, serine, histidine, arginine, proline and BCAA/AAA ratio were significantly decreased in two groups (P < 0.05-0.001). The Phel Tyr ratio in patients with sepsis was much higher than that in patients without sepsis on postburn days 14 and 21 (P < 0.05), while the BCAA/AAA ratio in patients with sepsis was much lower than that in patients without sepsis on postburn day 14 (P < 0.01). The level of proline in patients with sepsis was much higher than that in patients without sepsis on postburn days 3 and 7 (P < 0.05). It is suggested that these results, in collaboration with other clinical and laboratory findings, may be helpful in foretelling the probable development of sepsis in patients with major burns.
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PMID:[Changes in plasma free amino acid concentration in burned patients with sepsis]. 130 55

The genetic code, formerly thought to be frozen, is now known to be in a state of evolution. This was first shown in 1979 by Barrell et al. (G. Barrell, A. T. Bankier, and J. Drouin, Nature [London] 282:189-194, 1979), who found that the universal codons AUA (isoleucine) and UGA (stop) coded for methionine and tryptophan, respectively, in human mitochondria. Subsequent studies have shown that UGA codes for tryptophan in Mycoplasma spp. and in all nonplant mitochondria that have been examined. Universal stop codons UAA and UAG code for glutamine in ciliated protozoa (except Euplotes octacarinatus) and in a green alga, Acetabularia. E. octacarinatus uses UAA for stop and UGA for cysteine. Candida species, which are yeasts, use CUG (leucine) for serine. Other departures from the universal code, all in nonplant mitochondria, are CUN (leucine) for threonine (in yeasts), AAA (lysine) for asparagine (in platyhelminths and echinoderms), UAA (stop) for tyrosine (in planaria), and AGR (arginine) for serine (in several animal orders) and for stop (in vertebrates). We propose that the changes are typically preceded by loss of a codon from all coding sequences in an organism or organelle, often as a result of directional mutation pressure, accompanied by loss of the tRNA that translates the codon. The codon reappears later by conversion of another codon and emergence of a tRNA that translates the reappeared codon with a different assignment. Changes in release factors also contribute to these revised assignments. We also discuss the use of UGA (stop) as a selenocysteine codon and the early history of the code.
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PMID:Recent evidence for evolution of the genetic code. 157 11

Glycoprotein D (gD) of herpes simplex virus contains three utilized sites (Asn-X-Ser/Thr) for addition of asparagine-linked carbohydrates (N-CHO). Previously, we used oligonucleotide-directed mutagenesis to alter serine or threonine residues to alanine at each N-CHO addition site. Studies with monoclonal antibodies showed that a mutant protein lacking all three sites (now designated AAA) was structurally altered because of the amino acid change at residue 96 as well as the absence of the N-CHO. In this study, we constructed additional single mutations at site 1 (residues 94 and 96) and found that in most cases, the amino acid change itself adversely affected the conformation of gD. However, changing asparagine 94 to glutamine (Q) at site 1 had the least effect on gD. We constructed a second triple mutant, QAA, which lacked all three N-CHO signals. The antigenic conformation of QAA was similar to that of gD produced in the presence of tunicamycin (TM-gD). However, binding of MAbs to the AAA protein or to single mutants altered at site 1 was reduced compared with TM-gD. Wild-type gD and QAA proteins were equally susceptible to digestion by trypsin or Staphylococcus aureus V8 protease. In contrast, the AAA protein was more sensitive to trypsin but less sensitive to V8, again suggesting conformational alterations of the AAA protein. Despite what appeared to be large changes in structure, each mutant complemented the infectivity of a virus lacking gD (F-gD beta). We conclude that the N-CHO and amino acids at N-CHO site 1 play an important role in forming and/or maintaining gD structure, but none of the N-CHO are required for gD to function in the complementation assay.
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PMID:Absence of asparagine-linked oligosaccharides from glycoprotein D of herpes simplex virus type 1 results in a structurally altered but biologically active protein. 164 38

The universal genetic code is used without changes in chloroplasts and in mitochondria of green plants. Non-plant mitochondria use codes that include changes from the universal code. Chloroplasts use 31 anticodons in translating the code; a number smaller than that used by bacteria, because chloroplasts have eliminated 10 CNN anticodons that are found in bacteria. Green plant mitochondria (mt) obtain some tRNAs from the cytosol, and genes for some other tRNAs have been acquired from chloroplast DNA. The code in non-plant mt differs from the universal code in the following usages found in various organisms: UGA for Trp, AUA for Met, AGR for Ser and stop, AAA for Asn, CUN for Thr, and possibly UAA for Tyr. CGN codons are not used by Torulopsis yeast mt. Non-plant mt, e.g. in vertebrates, may use a minimum of 22 anticodons for complete translation of mRNA sequences. The following possible causes are regarded as contributing to changes in the non-plant mt: directional mutation pressure, genomic economization, changes in charging specificity of tRNAs, loss of release factor RF2, changes in RF1, changes in anticodons, loss of lysidine-forming enzyme system, and disappearance of codons from coding sequences.
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PMID:The genetic code in mitochondria and chloroplasts. 225 9

Free amino acid (AA) concentrations in plasma and quadriceps femoris muscle were determined in 19 healthy volunteers and in 16 patients with hepatic cirrhosis and portal hypertension. Nutritional state was impaired as judged by overt muscle wasting (9/16), triceps skinfold thickness less than 70% of normal in 8/14 (57%), and creatinine-height index below 70% in 5/12 (42%). In the plasma of patients the typical amino acid pattern of cirrhosis was to be observed: Elevation of tyrosine and methionine (p less than 0.01), uniform reduction of branched chain amino acids (p less than 0.001) resulting in a decreased molar ratio of BCAA/AAA from 2.85 +/- 0.05 in normal individuals to 1.35 +/- 0.12 in cirrhotics (p less than 0.001). Levels of the gluconeogenic AA glutamine, glutamate, aspartate, alanine, glycine, threonine, serine and lysine were lowered (p less than 0.05). In muscle of cirrhotics, intracellular AA concentrations exhibited a similar pattern with two major exceptions: Tyrosine and phenylalanine were augmented (p less than 0.001). Surprisingly, BCAA levels were altered heterogeneously; those of gluconeogenic BCAA decreased: Valine from 0.34 +/- 0.03 to 0.20 +/- 0.03 mmol/l (p less than 0.001), isoleucine 0.09 +/- 0.01 to 0.05 +/- 0.02 mmol/l. However, the concentration of ketogenic leucine remained unaltered in muscle. Nevertheless, the molar ratio of BCAA/AAA was considerably reduced from 3.70 +/- 0.04 to 0.81 +/- 0.08 (p less than 0.001). Most of the gluconeogenic AA exhibited reduced intramuscular concentrations, but glutamine levels were normal. The pattern of plasma and muscle free AA in hepatic cirrhosis is thus characterized by accumulation of aromatic AA and by depletion of gluconeogenic AA, especially BCAA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characteristic pattern of free amino acids in plasma and skeletal muscle in stable hepatic cirrhosis. 231 39

We generated variants of the human immunodeficiency virus type 1 (HIV-1) that are resistant to 2',3'-dideoxycytidine (ddC) and 2',3'-didehydro-3'-deoxythymidine (d4T) by in vitro selection in MT-4 cells. Portions of flanking protease and integrase sequences as well as the complete reverse transcriptase (RT) open-reading frame of these viruses were cloned and sequenced, using polymerase chain reaction (PCR)-based methods. Mutations were observed at amino acid position 65 (Lys-->Arg; AAA-->AGA) when ddC was employed in the selection procedure and at site 50 (Ile-->Thr; ATT-->ACT) when d4T was used. We confirmed the ability of these mutations to confer diminished sensitivity for these compounds by site-directed mutagenesis, in which these mutations were inserted into the pol gene of infectious recombinant HXB2-D DNA. Viruses that contained the site 65 mutation possessed approximately 5-10 fold resistance against ddC when compared with wild-type HXB2-D. The site 50 mutation conferred approximately 30-fold resistance to d4T in these same assays. Similar results were obtained using primary cord blood lymphocytes in drug resistance assays, indicating that these mutations could confer drug resistance in more than one cell type and that the respective mutations could be expressed in cells of primary origin. No cross-resistance against 3'-azido-3'-deoxythymidine (AZT) was noted for either the site 65 or 50 mutations.
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PMID:Identification of novel mutations that confer drug resistance in the human immunodeficiency virus polymerase gene. 751 78

Constitutively activating mutations have recently been identified in the thyrotropin receptor (TSHR) of hyperfunctioning thyroid adenomas and familial hyperthyroidism. In the present study, we evaluated the frequency of constitutively activating TSHR mutations in a large series of autonomously functioning thyroid nodules (AFTNs) in Japan. Forty-five AFTNs (38 solitary hyperfunctioning thyroid adenomas and 7 toxic multinodular goiters) were analyzed. Genomic DNA was extracted from paraffin-embedded tissue sections, from which DNA fragments encoding the mutational hot spots of the receptor (the third cytoplasmic loop and the sixth transmembrane segment) were amplified by polymerase chain reaction. In the single-stranded conformation polymorphism (SSCP) analysis, only one hyperfunctioning adenoma (no. 21) displayed a migration abnormality. In sequence analysis, an unusual mutation of alternate three-base deletions at nucleotides 1953-1957 (AAA GAT ACC to AAG TCC), resulting in one amino acid deletion (Asp at 619) and one conservative amino acid substitution (Thr to Ser at 620), was identified in tumor DNA but not in leukocyte DNA of no. 21. Further, the normal sequence in these regions was confirmed in 10 randomly selected samples with normal migrating patterns in SSCP analysis. The functional property of the mutant with delta 619 and T620S (designated TSHR delta 619) was then evaluated with in vitro mutagenesis and transfection studies. Unexpectedly, however, there were no significant differences in TSH binding affinity, and basal and TSH-stimulated levels of cAMP and inositol 1,4,5-triphosphate between the TSHR delta 619 and the wt-TSHR. In conclusion, the incidence of the constitutively activating TSHR mutations in AFTNs appears to be low in Japan. The oncogenic potential of a novel somatic mutant TSHR delta 619 identified in a hyperfunctioning adenoma in this study is at present uncertain because of its intact function.
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PMID:Rarity of oncogenic mutations in the thyrotropin receptor of autonomously functioning thyroid nodules in Japan. 767 2

Phosphorylation of the region containing Thr-494, Thr-495 and Thr-497, present in the catalytic domain of protein kinase C alpha (PKC alpha), is a preliminary event necessary for subsequent PKC activation [Cazaubon and Parker (1993) J. Biol. Chem. 268, 17559-17563]. To define the essential residues in this region, various combinations of alanine substitutions for threonine residues 494, 495 and 497 have been tested. These mutations yielded expressed polypeptides of 76 and 80 kDa in ratios that vary from 100% 80 kDa (wild-type kinase, active) to 100% 76 kDa (AAA mutant, inactive) with the hierarchy being wild-type PKC alpha (TTT), ATT, AAT, TTA, ATA, TAA, AAA (the nomenclature indicates the location of alanine residues substituted for Thr-494, Thr-495 and Thr-497 respectively). Only the mutants retaining Thr-497 displayed kinase activity in vitro. The results overall indicate that Thr-497 plays the dominant role in the regulation of PKC alpha activity but that in the wild-type protein, Thr-495 may also be important. Consistent with the need for phosphorylation in this region, an intrinsically active PKC alpha could be produced in bacteria by exchanging Thr-495 for a glutamic acid residue.
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PMID:Threonine-497 is a critical site for permissive activation of protein kinase C alpha. 804 86

The polymerase chain reaction (PCR) was used to amplify an approximately 1.2 kb DNA fragment encompassing the pre-S/S gene region of HBV DNA from serum of patients with acute hepatitis B virus infection. Nucleotide sequence analysis revealed a number of interesting features in the S gene region. Two Bam HI sites were located at nucleotide positions 557 and 872, respectively, in the S gene. Guanine (G) was found at nucleotide position 903 as part of AGA, the codon for arginine (R) corresponding to amino acid position 122 of the S protein. Adenine (A) was found at nucleotide position 1017 as part of AAA, the codon for lysine (K) corresponding to amino acid position 160 of the S protein. Nucleotide sequence alignment revealed a 97% homology to the corresponding domain of an HBVadw genome (clone pFDW294). Within the second loop of the "a" determinant, two mutations resulting in substitution of serine or threonine with the hydrophobic amino acids, methionine at position 143 and with alanine in place of glycine at position 145, are predicted from the consensus nucleotide sequence of the PCR-derived clones. Subtyping with monoclonal antibodies showed that the HBsAg was of the ayw subtype.
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PMID:Variant of hepatitis B virus isolated in Zimbabwe. 830 23

Sequence analysis of the tyrosinase coding region from an individual with tyrosinase-negative oculocutaneous albinism revealed that the patient was a compound heterozygote. One allele carried a C--> A single-base substitution in codon 355 of exon 3, and the other carried a two-nucleotide deletion in exon 1. The nucleotide substitution caused a putative amino acid change from threonine (ACA) to lysine (AAA), abolishing a signal for N-glycosylation. The two base-pair deletion caused a frameshift, creating a putative premature termination signal at codon 226. The melanocytes from the proband and her affected brother were amelanotic and devoid of measurable tyrosinase activity. Moreover, gel electrophoretic analysis of the immunoprecipitated proband tyrosinase showed that the protein was not processed to the mature glycosylated form, confirming the predicted consequence of the amino acid change. The two-base deletion on the homologous allele was detected only by sequencing genomic DNA. The transcript of this allele was not represented in the cDNA library and could not be detected by PCR mRNA, and the putative truncated protein (approximately 25 kDa) was not present in immunoprecipitates, suggesting that the allele with the missense mutation may be preferentially expressed.
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PMID:Molecular analyses of a tyrosinase-negative albino family. 843 Jul 1


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