Stoicheiometry and kinetics of the prolyl 4-hydroxylase partial reaction

Jong, Luitzen de; Kemp, A.

doi:10.1016/0167-4838(84)90113-4

Cited by 83 publications

(46 citation statements)

References 16 publications

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“…without subsequent hydroxylation (Tuderman et al, 1977;Rao & Adams, 1978;Counts et al, 1978). Ascorbate serves as a specific alternative oxygen acceptor in such cycles (Myllyla et al, 1984;De Jong & Kemp, 1984), and in its absence the enzyme is rapidly inactivated by self-oxidation (Myllyli et al, 1978;De Jong et al, 1982).…”

Section: Introductionmentioning

confidence: 99%

Time-dependent inactivation of chick-embryo prolyl 4-hydroxylase by coumalic acid. Evidence for a syncatalytic mechanism

Günzler¹,

Hanauske-Abel²,

Myllylä³

et al. 1987

Biochemical Journal

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From the structure-activity relationships of known competitive inhibitors, coumalic acid (2-oxo-1,2H-pyran-5-carboxylic acid) was deduced to be a potential syncatalytic inhibitor for chick-embryo prolyl 4-hydroxylase. The compound caused time-dependent inactivation, the reaction rate being first-order. The inactivation constant was 0.094 min-1, the Ki 17 mm and the bimolecular rate constant 0.09 M-1 -s-1. Human prolyl 4-hydroxylase and chick embryo lysyl hydroxylase were also inactivated, though to a lesser extent. Inactivation could be prevented by adding high concentrations of 2-oxoglutarate or its competitive analogues to the reaction mixture. In Lineweaver-Burk kinetics, coumalic acid displayed S-parabolic competitive inhibition with respect to 2-oxoglutarate. The inactivation reaction had cofactor requirements similar to those for the decarboxylation of 2-oxoglutarate. Enzymic activity was partially preserved in the absence of iron, but the rescue was incomplete, owing to decreased stability of the enzyme under this condition. Coumalic acid also decreased the electrophoretic mobility of the a-subunit, but the f-subunit was not affected. Prolonged incubation of coumalic acid above pH 6.8 led to loss of its inactivating potency, owing to hydrolysis. It is concluded that the inactivation of prolyl 4-hydroxylase by coumalic acid is due to a syncatalytic mechanism. The data also suggest that the 2-oxoglutarate-binding site of the enzyme is located within the a-subunit.

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Section: Introductionmentioning

confidence: 99%

Time-dependent inactivation of chick-embryo prolyl 4-hydroxylase by coumalic acid. Evidence for a syncatalytic mechanism

Günzler¹,

Hanauske-Abel²,

Myllylä³

et al. 1987

Biochemical Journal

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“…Consequences of this response in alpine marmots remain unclear. Although marmots, like other hibernators, are capable of adjusting their body temperature over a wide range, several studies in humans indicate a negative effect of hypothermia during surgery on the immune system (Wenisch et al, 1996), wound healing (De Jong and Kemp, 1984), blood clotting (Kurz, 1997), and general recovery (Lenhardt et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Three Combinations of Anesthetics for Use in Free-Ranging Alpine Marmots (Marmota Marmota)

Beiglböck

Zenker

2003

Journal of Wildlife Diseases

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From April 1998 to September 2000, 241 free-ranging alpine marmots (Marmota marmota) were anesthetized in the course of a field project using either xylazine plus ketamine (XK), medetomidine plus ketamine (MK), or xylazine plus a 1:1 mixture of zolazepam and tiletamine (XZT). For each of the combinations, the respective doses for short term and long-term surgery were established and seasonal variations in the amount of drugs needed were assessed. No fatalities occurred, and doses for efficient and safe anesthesia in spring were as follows (XK, MK, and XZT, respectively, in mg/kg body mass): short term surgery 3ϩ40, 0.25ϩ35, and 3ϩ15; long term surgery 20ϩ80, 0.5ϩ70, and 10ϩ20. In late summer/autumn, higher doses (20ϩ60, 0.2ϩ60, and 10ϩ15 for short term surgery) had to be administered, probably due to increase of marmots' body fat content. Heart rate, respiratory rate, rectal temperature, palpebral reflex, muscle relaxation, and analgesia were monitored to evaluate the animals' responses to each of the drug combinations. Hypothermia was induced by all combinations and heart rate significantly decreased during anesthesia, especially in marmots receiving MK. Respiratory rate was highly variable and no significant differences between the drugs were found. Muscle relaxation was rather poor in marmots anesthetized with XK. The XZT combination tended to have a longer induction period but was found to subsequently depress the palpebral reflex and induce muscle relaxation and analgesia very efficiently. We conclude that, regardless of the anesthetics used, doses should always be adjusted to the planned manipulations, the marmots' nutritional state, and to the time of year. Furthermore, close monitoring of physiologic parameters, especially body temperature, should be guaranteed. On the basis of physiologic and behavioral responses, XZT is the most effective drug combination for anesthetizing alpine marmots, especially for long term, potentially painful procedures.

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“…The prolyl and lysyl hydroxylases that catalyze this reaction depend on the substrate oxygen [49]. The Km for O 2 of prolyl hydroxylase has been variously estimated at 20, 25, and 100 mmHg [50][51][52]. Even using the most conservative estimate, proline hydroxylation of collagen will be PO 2 -dependent through the range of 0 to at least 200 mmHg, with 90% of the effect occurring by 90 mmHg.…”

Section: Supplemental Oxygen Tissue Oxygenationmentioning

confidence: 99%

Non-pharmacologic Prevention of Surgical Wound Infection

Sessler

2006

Anesthesiology Clinics of North America

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Wound infections are serious and relatively common postoperative complications. They are generally detected five to nine days after surgery and are usually attributed, even by surgeons, to poor surgical technique or failure to maintain sterility. However, it has been known for decades that all wounds become contaminated, often by bacteria from the skin or within the patient, and that it is host defense mechanisms that prevent most contamination from developing into clinical infections. Host defense is especially important during the initial hours following contamination, i.e., the immediate perioperative period.As might thus be expected, factors that improve host defense reduce infection risk. Many of these are under the direct control of anesthesiologists and are at least as important as appropriate use of prophylactic antibiotics, which halve infection risk [1]. This article will review nonpharmacologic methods of reducing infection risk, with special emphasis on methods available to anesthesiologists.

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Stoicheiometry and kinetics of the prolyl 4-hydroxylase partial reaction

Cited by 83 publications

References 16 publications

Time-dependent inactivation of chick-embryo prolyl 4-hydroxylase by coumalic acid. Evidence for a syncatalytic mechanism

Time-dependent inactivation of chick-embryo prolyl 4-hydroxylase by coumalic acid. Evidence for a syncatalytic mechanism

Evaluation of Three Combinations of Anesthetics for Use in Free-Ranging Alpine Marmots (Marmota Marmota)

Non-pharmacologic Prevention of Surgical Wound Infection

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