Disease relevance of L-Gulono-gamma-lactone

• Mycobacterium tuberculosis possesses a functional enzyme for the synthesis of vitamin C, L-gulono-1,4-lactone dehydrogenase [1].
• A blast search using the rat l-gulono-1,4-lactone oxidase sequence revealed the presence of closely related orthologs in a limited number of bacterial species, including several pathogens of human lungs, such as Mycobacterium tuberculosis, Pseudomonas aeruginosa, Burkholderia cepacia and Bacillus anthracis [1].

High impact information on L-Gulono-gamma-lactone

• The lactonase reaction with l-gulono-gamma-lactone is the penultimate step in l-ascorbic acid (AA) biosynthesis, and the essential role of SMP30 in this synthetic process was verified here by a nutritional study using SMP30 knockout mice [2].
• To test the effect of this mutation on the expression of L-gulono-gamma-lactone oxidase, we inserted a region of the cDNAs coding for normal and mutant L-gulono-gamma-lactone oxidases into an expression vector, pSVL, and transfected COS-1 cells with such vectors [3].
• Sequencing of polymerase chain reaction-amplified cDNAs for mutant and normal rat L-gulono-gamma-lactone oxidases demonstrated that the mutant cDNA has a single base mutation from G to A at nucleotide 182, which mutation alters the 61st amino acid residue from Cys to Tyr [3].
• Cells infected with Gulo-expressing vectors overexpressed an FAD-containing protein that corresponded in size to that predicted for recombinant GULO protein and expressed a functional enzyme as measured by the conversion of l-gulono-gamma-lactone to ascorbic acid in cell-free extracts [4].
• This was demonstrated by the absence of L-gulonolactone oxidase activity, the enzyme responsible for the biosynthesis of vitamin C, in liver or kidney of oscars and by a feeding trial in which oscars without vitamin C dietary supplementation developed clinical deficiency signs [5].

Biological context of L-Gulono-gamma-lactone

• To restore AA synthesis pathway, bovine aortic endothelial cells were transfected with the plasmid vector encoding L-gulono-1,4-lactone oxidase (GULO, EC 1.1.3.8), the missing enzyme converting L-gulono-1,4-lactone (GUL) to AA [6].
• Deduced amino acid sequence of the gene has 25.3% identity and 68.1% similarity to that of rat L-gulonolactone oxidase at the overall amino acids [7].
• The 164-nucleotide sequence of exon X of the gene was compared among human, chimpanzee, orangutan, and macaque, and it was found that nucleotide substitutions had occurred at random throughout the sequence with a single nucleotide deletion, indicating that the primate L-gulono-gamma-lactone oxidase genes are a typical example of pseudogene [8].
• Homo sapiens' gene pool contains a defective gene for the synthesis of the active enzyme protein, L-gulonolactone oxidase(GLO) [9].
• The genome of M. tuberculosis, the etiologic agent of tuberculosis, encodes a protein (Rv1771) that shows 32% identity with the rat l-gulono-1,4-lactone oxidase protein [1].

Anatomical context of L-Gulono-gamma-lactone

• Ascorbic acid synthesis due to L-gulono-1,4-lactone oxidase expression enhances NO production in endothelial cells [6].
• The last step in the pathway of vitamin C synthesis is the oxidation of l-gulonolactone to l-ascorbic acid by l-gulonolactone oxidase, an enzyme associated with the endoplasmic reticulum membrane and deficient in man, guinea pig and other species due to mutations in its gene [10].

Associations of L-Gulono-gamma-lactone with other chemical compounds

• Glutaraldehyde-reacted immunoprecipitates of L-gulonolactone oxidase are suitable for administration to guinea pigs [11].

Gene context of L-Gulono-gamma-lactone

• We conclude that GLDHase, L-gulono-gamma-lactone oxidase and L-galactono-gamma-lactone oxidase are homologous in spite of the difference in substrates and electron acceptors [12].
• 5. The New Zealand White breed of domestic rabbit (Oryctolagus cuniculus) has considerably higher levels of L-gulonolactone oxidase and liver ascorbate than does the Dutch breed [13].

Analytical, diagnostic and therapeutic context of L-Gulono-gamma-lactone

• Intraperitoneal injection of this altered enzyme to animals supplemented with L-gulonolactone increases plasma concentrations of the vitamin [14].

References