Disease relevance of AMD1

• Extracts of Escherichia coli containing a plasmid with the gene for yeast AMP deaminase contained only the unproteolyzed enzyme, Mr 100,000 [1].

High impact information on AMD1

• The AMP deaminase gene was mapped to chromosome XIII of Saccharomyces cerevisiae strain JM1901 [2].
• The presence of a regulated AMP deaminase in S. pombe supports the hypothesis that eukaryotes regulate adenine nucleotide pools by the activity of AMP deaminase [2].
• The results establish that S. pombe contains an AMP deaminase with catalytic properties similar to that from S. cerevisiae, even though the DNA sequences of the genes and the immunoreactivity of the protein from S. pombe differs considerably from the AMP deaminase of S. cerevisiae [2].
• Genetic analysis of the pathways of purine metabolism in S. pombe (Pourquié, J., and Heslot, H. (1971) Genet. Res. 18, 33-44) had indicated the absence of AMP deaminase [2].
• The traditional cooperative binding models of allosteric regulation do not apply to yeast AMP deaminase, which regulates catalytic activity by kinetic control of product formation [3].

Biological context of AMD1

• PRP28 and AMD1 genes map to the right arm of chromosome IV next to sup2, which encodes a tyrosine tRNA [4].
• Allosteric regulation of yeast AMP deaminase is of physiological significance, since expression of the gene is constitutive (Meyer, S [1].
• Alignment of the amino acid sequence for yeast AMP deaminase with that for mouse adenosine deaminase demonstrates conservation of the amino acids known from the X-ray crystal structure to bind to the zinc and to a transition-state analogue [5].
• The open reading frame corresponding to AMD codes for a protein of 810 amino acids, molecular weight 93,286 [6].
• The gene for AMP deaminase was located in a lambda gt11 library of yeast genomic DNA, and a DNA fragment from the lambda gt11 clone was used to locate homologous DNA in a yeast genomic library in the centromeric plasmid YCp50, a yeast-Escherichia coli shuttle vector [6].

Anatomical context of AMD1

• EMBRYONIC FACTOR 1 encodes an AMP deaminase and is essential for the zygote to embryo transition in Arabidopsis [7].
• AMP deaminase (AMP-D) plays a critical role in energy metabolism in skeletal muscle [8].

Associations of AMD1 with chemical compounds

• This report describes 1) the role of AMP deaminase in adenylate metabolism in yeast cell extracts, 2) a method for large scale purification of the enzyme, 3) the kinetic properties of native and proteolyzed enzymes, 4) the kinetic reaction mechanism, and 5) regulatory interactions with ATP, GTP, MgATP, ADP, and PO4 [1].
• On the basis of these similarities, yeast AMP deaminase is also proposed to use a Zn(2+)-activated water molecule to attack C6 of AMP with the displacement of NH3 [5].
• The role of fatty acid and citrate on the interaction of the AMP deaminase (EC 3.5.4.6) reaction with glycolysis was investigated using permeabilized yeast cells [9].
• 4) A simple Michaelis-Menten relationship was observed between the various levels of ammonium ion and of fructose 1,6-biphosphate formed in situ, indicating that phosphofructokinase activity or glycolytic flux was dependent upon the level of ammonium produced through the action of AMP deaminase [10].
• (b) Linolenate inhibited AMP deaminase activity in situ, resulting in the subsequent decrease in ammonium production, which reduced the activity of 6-phosphofructokinase (EC 2.7.1.11), whereas linolenate itself had no ability to inhibit the phosphofructokinase activity in the presence of excess ammonium concentration [9].

Regulatory relationships of AMD1

• (c) Pi activated phosphofructokinase (EC 2.7.1.11) and inhibited AMP deaminase activity [11].
• Role of AMP deaminase reaction in the control of fructose 1,6-bisphosphatase activity in yeast [11].
• Identification of a noncatalytic domain in AMP deaminase that influences binding to myosin [8].

Other interactions of AMD1

• Thus, it appears that AMD1 might be the structural gene for alpha-mannosidase [12].
• 1) The addition of polyamine activated AMP deaminase in situ, resulting in the subsequent increase in ammonium production, which can stimulate the activity of 6-phosphofructokinase (EC 2.7.1.11) and pyruvate kinase (EC 2.7.1.40) [10].
• (a) Fructose 1,6-bisphosphatase (EC 3.1.3.11) was inhibited only a little by AMP, which was readily degraded by AMP deaminase under the in situ conditions [11].

Analytical, diagnostic and therapeutic context of AMD1

• A yeast strain deficient in AMP deaminase activity was produced and shown to be deficient in AMP deaminase protein by Western blot analysis [6].

References