Disease relevance of AMPD3

• Erythrocyte AMP deaminase [isoform E (AMPD3)] is activated in response to increased intracellular calcium levels in Tarui's disease, following exposure of ionophore-treated cells to extracellular calcium, and by the addition of calcium to freshly prepared hemolysates [1].
• Conclusions Along with the activation of AMPD3, ischemia-reperfusion-induced lung inflammation is associated with increased MPO activity and TNF-alpha level [2].
• For the remaining 8 genes (or their human homolog), RT-PCR analysis was performed on RNA from human colon cancer cell lines and matched normal and tumor colon cancer tissues from human patients, revealing three novel targets (rat brain serine protease2, AMP deaminase 3, and cartilage link protein 1) [3].

High impact information on AMPD3

• The binding of purified human erythrocyte AMP deaminase to human erythrocyte membranes and the effect of binding on enzyme catalytic activity was investigated [4].
• A point mutation responsible for human erythrocyte AMP deaminase deficiency [5].
• Finally, AMPD1 and a series of N-truncated AMPD3 enzymes are used to show that these behaviors are specific to isoform E and require up to 48 N-terminal amino acids, even though this stretch of sequence contains no histidine residues [6].
• N-terminal sequence and distal histidine residues are responsible for pH-regulated cytoplasmic membrane binding of human AMP deaminase isoform E [6].
• Mammalian AMP deaminase 3 (AMPD3) enzymes reportedly bind to intracellular membranes, plasma lipid vesicles, and artificial lipid bilayers with associated alterations in enzyme conformation and function [6].

Biological context of AMPD3

• RNase protection analyses and the partial characterization of human AMPD3 genomic clones demonstrate alternative splicing of three different 5'-terminal exons [7].
• Nucleotide sequence alignments between AMPD3 cDNAs isolated from several human libraries indicate three different extreme 5'-ends [7].
• Alternate forms of the AMPD3 cDNAs contain a common 2301-bp open reading frame (ORF) and 3'-untranslated region of 1245 bp [7].
• Examination of relative rat AMPD3 gene expression shows (1) variable patterns of alternative mRNA abundance across adult tissues, (2) developmental regulation in skeletal muscle and liver, and (3) greater mRNA abundance in adult red (soleus) than in mixed (plantaris) and white (outer gastrocnemius) skeletal muscle [8].
• Across the region that is common to all rat and human AMPD3 cDNA species, nucleotide and predicted amino acid sequences are 89% and 93% identical respectively, although the rat open reading frame is lacking two separate in-frame codons in the 5' end [8].

Anatomical context of AMPD3

• This study uses erythrocyte ghosts to characterize the reversible cytoplasmic membrane association of human full-sized recombinant isoform E (AMPD3) [6].
• These results suggest that expression of the AMPD1 and AMPD3 genes may be coordinated in myocytes to effect production of an AMPD holoenzyme of varying subunit composition [9].
• The same point mutation was detected in both of the two B-lymphoblast cell lines derived from the complete deficiency of human erythrocyte AMP deaminase: a single nucleotide substitution of C to T resulted in an amino acid change of Arg to Cys at the codon 573 [5].

Associations of AMPD3 with chemical compounds

• This regulatory mechanism could also play an important role in purine metabolism in other human tissues and cells where the AMPD3 gene is expressed [1].
• Phosphatidylinositol 4,5-bisphosphate is the most potent inhibitor, effecting pure noncompetitive inhibition of the wild type human AMPD3 recombinant enzyme with a K(i) of 110 nM [10].
• The predicted human AMPD3 sequence contains pleckstrin homology domains and (R/K)X(n)(R/K)XKK sequences, both of which are characterized phosphoinositide-binding motifs [10].
• Remote Reperfusion Lung Injury is Associated With AMP Deaminase 3 Activation and Attenuated by Inosine Monophosphate [2].

Other interactions of AMPD3

• This study identifies a third human AMP deaminase gene, AMPD3 [7].
• Conversely, residues 129-183 in the AMPD2 polypeptide reduce actomyosin binding of isoform L. In addition, residues 1-48 in the AMPD3 polypeptide dramatically suppress contractile protein binding of isoform E, thus allowing this enzyme to participate in other intracellular interactions [11].
• Exposure to a calmodulin antagonist significantly slows IMP accumulation during experimental energy imbalance in patients' cells to levels that are similar to those in untreated controls, implying that Ca2+-calmodulin is involved in erythrocyte AMP deaminase activation in familial phosphofructokinase deficiency [12].

Analytical, diagnostic and therapeutic context of AMPD3

• Western blot analyses detect anti-E-specific immunoreactivity in affinity-purified extracts derived from the bacterial expression of a truncated AMPD3 cDNA [7].
• Four separate DNA fragments covering the entire coding region of AMPD-3 cDNA were amplified using polymerase chain reaction (PCR) technique and sequenced directly [5].

References