The human L-threonine 3-dehydrogenase gene is an expressed pseudogene

The human TDH gene is located at 8p23-22 and has 8 exons spanning 10 kb that would have been expected to encode a 369 residue ORF. However, 2 cDNA TDH transcripts encode truncated proteins of 157 and 230 residues. These truncated proteins are the result of 3 mutations within the gene. There is a SNP, A to G, present in the genomic DNA sequence of some individuals which results in the loss of the acceptor splice site preceding exon 4. The acceptor splice site preceding exon 6 was lost in all 23 individuals genotyped and there is an in-frame stop codon in exon 6 (CGA to TGA) resulting in arginine-214 being replaced by a stop codon. These truncated proteins would be non-functional since they have lost part of the NAD+ binding motif and the COOH terminal domain that is thought to be involved in binding L-threonine. TDH mRNA was present in all tissues examined.The human L-threonine 3-dehydrogenase gene is an expressed pseudogene having lost the splice acceptor site preceding exon 6 and codon arginine-214 (CGA) is mutated to a stop codon (TGA).Liver failure is a cause of considerable mortality; therefore bioartificial livers may offer significant therapeutic benefit. Porcine-derived hepatocytes are being used in clinical studies of bioartificial livers [1,2]. There may, however, be significant differences in the activities of liver enzymes between species [3]. These differences are also important considerations when the pharmaceutical industry conducts new drug metabolism and pharmacokinetic studies on key mammal species [4].The liver plays a critical role in regulating the circulating concentrations of amino acids. The regulation of amino acid supply to bioartificial organs and maintaining the activity of the amino acid-metabolising enzymes will be important in their development. Active maintenance of the optimal amino acid concentrations will offer the possibility of prolonging the differentiated function of hepatocytes in bioartificial livers [5].L-threonine is one of