Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036474 (scurvy)
 685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We originally identified senescence marker protein 30 (SMP30) as a distinctive protein whose expression decreases in an androgen-independent manner with aging. Here, we report its sequence homology found in two kinds of bacterial gluconolactonases (GNLs) by using the blast search. Then, through a biochemical study, we identify SMP30 as the lactone-hydrolyzing enzyme GNL of animal species. SMP30 purified from the rat liver had lactonase activity toward various aldonolactones, such as d- and l-glucono-delta-lactone, d- and l-gulono-gamma-lactone, and d- and l-galactono-gamma-lactone, with a requirement for Zn(2+) or Mn(2+) as a cofactor. Furthermore, in SMP30 knockout mice, no GNL activity was detectable in the liver. Thus, we conclude that SMP30 is a unique GNL in the liver. 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. These knockout mice (n = 6), fed a vitamin C-deficient diet, did not thrive; i.e., they displayed symptoms of scurvy such as bone fracture and rachitic rosary and then died by 135 days after the start of receiving the deficient diet. The AA levels in their livers and kidneys at the time of death were <1.6% of those in WT control mice. In addition, by using the SMP30 knockout mouse, we demonstrate that the alternative pathway of AA synthesis involving d-glucurono-gamma-lactone operates in vivo, although its flux is fairly small.
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PMID:Senescence marker protein 30 functions as gluconolactonase in L-ascorbic acid biosynthesis, and its knockout mice are prone to scurvy. 1658 34

A novel rat liver protein of 30 kDa, SMP30 decreases with aging. This protein is expressed most prominently in the liver and kidneys among the various organs. Its gene is located on the X chromosome. No functional domain was recognized in the entire amino acid sequence. Recently, we found a homology between rat SMP30 and two species of bacterial gluconolactonase (EC 3.1.1.17). The lactonase reaction with L-gulono-gamma-lactone is the penultimate step in vitamin C (L-ascorbic acid) biosynthesis. SMP30-knockout (KO) mice fed a vitamin C-deficient diet displayed symptoms of scurvy. In SMP30-KO mice, hepatocytes were more susceptible to apoptosis induced by TNF-alpha plus actinomycin D than hepatocytes from wild-type mice. Two morphological features considered to be a hallmark of senescence are apparent in SMP30-KO mice. At 12 months of age, SMP30-knockout mice had clearly visible deposits of lipofuscin and senescence-associated beta-galactosidase (SA-beta-GAL) in their renal tubular epithelia. These features are compatible with high electron dense deposits in lysosomes. This observation suggests that the SMP30-knockout mouse is a useful model of ordinal senescence.
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PMID:Pathophysiological significance of senescence marker protein-30. 2059 Aug 46