MetaCyc Pathway: hypusine biosynthesis
Inferred from experiment

Enzyme View:

Pathway diagram: hypusine biosynthesis

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: BiosynthesisAmino Acids BiosynthesisModification of Amino Acids Within Proteins

Some taxa known to possess this pathway include : Arabidopsis, Cryptosporidium parvum, Homo sapiens, Nicotiana tabacum, Solanum lycopersicum

Expected Taxonomic Range: Eukaryota

The eukaryotic translation initiation factor 5A (eIF-5A), which is present in all eukaryotic cells, must be activated by post translational modification before it can participate in the initiation of protein synthesis. The modification involves the addition of a butylamine residue (derived from spermidine) to a highly conserved lysine in the eIF-5A protein [Wang01c]. This results in the formation of an unusual amino acid called hypusine. The biosynthesis of hypusine occurs exclusively within the eIF-5A precursor, and is catalyzed by two enzymatic steps, deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH) [Ober99a].

The biosynthesis of hypusine is found in all eukaryotes and the DHS and DOHH enzymes are highly conserved, indicating that the fundamental cellular function of elF5A is maintained from plants to mammals. DHS enzymes have been isolated and characterized from several animals and plants. The second enzyme (DOHH) has been charaterized from mammals, and homologs were identified in the Arabidopsis and Oryza genomes.

In tomato there is an increase in the abundance of DHS mRNA as well as elf5A mRNA in senescing flowers and fruits and in environmentally stressed leaves, suggesting that this enzyme plays a role in programmed cell death [Wang01c]. The antisense suppression of deoxyhypusine synthase in tomato dealys fruit softening and alters growth and development [Wang05].

The strict substrate specificity for hypusine modification provides possible drug targeting of these enzymes, particularly in aberrant cell proliferation [Wolff07].

Created 28-Apr-2008 by Pujar A, Cornell University
Revised 21-Oct-2013 by Caspi R, SRI International


Ober99a: Ober D, Hartmann T (1999). "Deoxyhypusine synthase from tobacco. cDNA isolation, characterization, and bacterial expression of an enzyme with extended substrate specificity." J Biol Chem 274(45);32040-7. PMID: 10542236

Wang01c: Wang TW, Lu L, Wang D, Thompson JE (2001). "Isolation and characterization of senescence-induced cDNAs encoding deoxyhypusine synthase and eucaryotic translation initiation factor 5A from tomato." J Biol Chem 276(20);17541-9. PMID: 11278418

Wang05: Wang TW, Zhang CG, Wu W, Nowack LM, Madey E, Thompson JE (2005). "Antisense suppression of deoxyhypusine synthase in tomato delays fruit softening and alters growth and development." Plant Physiol 138(3);1372-82. PMID: 15951486

Wolff07: Wolff EC, Kang KR, Kim YS, Park MH (2007). "Posttranslational synthesis of hypusine: evolutionary progression and specificity of the hypusine modification." Amino Acids 33(2);341-50. PMID: 17476569

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Abrahamsen04: Abrahamsen MS, Templeton TJ, Enomoto S, Abrahante JE, Zhu G, Lancto CA, Deng M, Liu C, Widmer G, Tzipori S, Buck GA, Xu P, Bankier AT, Dear PH, Konfortov BA, Spriggs HF, Iyer L, Anantharaman V, Aravind L, Kapur V (2004). "Complete genome sequence of the apicomplexan, Cryptosporidium parvum." Science 304(5669);441-5. PMID: 15044751

Joe95: Joe YA, Wolff EC, Park MH (1995). "Cloning and expression of human deoxyhypusine synthase cDNA. Structure-function studies with the recombinant enzyme and mutant proteins." J Biol Chem 270(38);22386-92. PMID: 7673224

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Mittal14: Mittal N, Morada M, Tripathi P, Gowri VS, Mandal S, Quirch A, Park MH, Yarlett N, Madhubala R (2014). "Cryptosporidium parvum has an active hypusine biosynthesis pathway." Mol Biochem Parasitol 195(1);14-22. PMID: 24893338

Park06b: Park JH, Aravind L, Wolff EC, Kaevel J, Kim YS, Park MH (2006). "Molecular cloning, expression, and structural prediction of deoxyhypusine hydroxylase: a HEAT-repeat-containing metalloenzyme." Proc Natl Acad Sci U S A 103(1);51-6. PMID: 16371467

Wolff97: Wolff EC, Folk JE, Park MH (1997). "Enzyme-substrate intermediate formation at lysine 329 of human deoxyhypusine synthase." J Biol Chem 272(25);15865-71. PMID: 9188485

Yoshioka90: Yoshioka H, Ramirez F (1990). "Pro-alpha 1(XI) collagen. Structure of the amino-terminal propeptide and expression of the gene in tumor cell lines." J Biol Chem 265(11);6423-6. PMID: 1690726

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by Pathway Tools version 19.5 (software by SRI International) on Thu May 5, 2016, biocyc13.