Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.64 (proteinase K)
 4,071 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lipoamidase, which hydrolyses such substrates as lipoamide, lipoylmethyl ester, lipoyllysine, and lipoyl 4-aminobenzoate (LPAB), was purified from human serum through use of synthetic substrate LPAB. The purified human serum lipoamidase showed lipoyllysine hydrolase activity (Km = 435 microM, Vmax = 64.5 nmol/min per mg of protein). The purified enzyme did not liberate the free form of lipoic acid from bovine heart pyruvate dehydrogenase (PDH). PDH was hydrolyzed quantitatively by proteinase K to lipoyllysine, which was determined by the HPLC method. Although liberation of lipoate from various lengths of lipoyl-peptides has not been tested yet, it is likely that lipoamidase requires proteinase(s) before the liberation of free lipoic acid from the enzymes.
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PMID:Liberation of lipoate by human serum lipoamidase from bovine heart pyruvate dehydrogenase. 250 79

We report here that sequential digestion with endonuclease III, formamidopyrimidine-DNA glycosylase, and proteinase K in Tris buffer markedly increased the sensitivity for detecting DNA damage in arsenic-treated cells. These three enzymes increased DNA strand breaks in an additive manner. By using this sequential-enzyme-digestion comet assay, we demonstrated that trivalent inorganic arsenic induced more DNA damage than monomethylarsonous acid, monomethylarsonic acid, and dimethylarsinic acid in human blood cell lines. However, trivalent inorganic arsenic was far less potent than monomethylarsonous acid in inhibiting pyruvate dehydrogenase activity. Therefore, different mechanisms are involved in inhibiting pyruvate dehydrogenase activity and inducing DNA damage. Our results also indicate while trivalent inorganic arsenic induced more endonuclease III-digestible adducts, monomethylarsonous acid and monomethylarsonic acid induced more proteinase K-digestible adducts. These results suggest there is a difference in the mechanism for inducing DNA damage between inorganic and organic methylated arsenic compounds.
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PMID:Endonuclease III, formamidopyrimidine-DNA glycosylase, and proteinase K additively enhance arsenic-induced DNA strand breaks in human cells. 1238 22

This study examines the role of c-jun N-terminal kinase (JNK) in mitochondrial signaling and bioenergetics in primary cortical neurons and isolated rat brain mitochondria. Exposure of neurons to either anisomycin (an activator of JNK/p38 mitogen-activated protein kinases) or H2O2 resulted in activation (phosphorylation) of JNK (mostly p46(JNK1)) and its translocation to mitochondria. Experiments with mitochondria isolated from either rat brain or primary cortical neurons and incubated with proteinase K revealed that phosphorylated JNK was associated with the outer mitochondrial membrane; this association resulted in the phosphorylation of the E(1alpha) subunit of pyruvate dehydrogenase, a key enzyme that catalyzes the oxidative decarboxylation of pyruvate and that links two major metabolic pathways: glycolysis and the tricarboxylic acid cycle. JNK-mediated phosphorylation of pyruvate dehydrogenase was not observed in experiments carried out with mitoplasts, thus suggesting the requirement of intact, functional mitochondria for this effect. JNK-mediated phosphorylation of pyruvate dehydrogenase was associated with a decline in its activity and, consequently, a shift to anaerobic pyruvate metabolism: the latter was confirmed by increased accumulation of lactic acid and decreased overall energy production (ATP levels). Pyruvate dehydrogenase appears to be a specific phosphorylation target for JNK, for other kinases, such as protein kinase A and protein kinase C did not elicit pyruvate dehydrogenase phosphorylation and did not decrease the activity of the complex. These results suggest that JNK mediates a signaling pathway that regulates metabolic functions in mitochondria as part of a network that coordinates cytosolic and mitochondrial processes relevant for cell function.
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PMID:c-Jun N-terminal kinase regulates mitochondrial bioenergetics by modulating pyruvate dehydrogenase activity in primary cortical neurons. 1794 12