Intracellular distribution of vitamin K in the rat

Bell, Robert G.; Matschiner, John T.

doi:10.1016/0304-4165(69)90274-8

Cited by 23 publications

(5 citation statements)

References 15 publications

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“…Vitamin K is rather widely distributed (Bell & Matschiner, 1969;Nyquist et al, 1971;Knauer et al, 1976) among membrane organelles and concentrated in microsomes and mitochondria. A number of variables, including warfarin treatment, have been found to be without effect on this distribution (Thierry & Suttie, 1971).…”

mentioning

confidence: 99%

Vitamin K dependent carboxylase: subcellular location of the carboxylase and enzymes involved in Vitamin K metabolism in rat liver

Carlisle¹,

Suttie²

1980

Biochemistry

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Vitamin K dependent carboxylation of an exogenous peptide substrate and endogenous protein substrates, vitamin K epoxidation, and reduction of vitamin K epoxide were measured in subcellular fractions from rat liver. The rough microsomal fraction was highly enriched in all four activities; lower levels were found in smooth microsomes. Mitochondria, nuclei, and cytosol had negligible activities. The addition of 0.2% Triton X-100 to intact microsomes resulted in a 10-20-fold stimulation in carboxylation of a peptide substrate. This marked latency suggests that the active site of the carboxylase may be accessible only from the lumen of the microsomal membrane. A lumen-facing orientation of the carboxylase was also supported by its inaccessibility to trypsin in intact microsomes contrasted with marked inhibition by trypsin in detergent-permeabilized microsomes. Vitamin K epoxidase and epoxide reductase activities were also inhibited by trypsin much more effectively in permeabilized than in intact microsomes, although some degree of exposure at the cytosolic surface was also indicated. These data suggest that carboxylation is an early event in prothrombin synthesis occurring primarily on the lumen side of the rough endoplasmic reticulum membrane. The location of the vitamin K epoxidation-reduction cycle enzymes is consistent with their possible role in the carboxylation reaction.

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confidence: 99%

Vitamin K dependent carboxylase: subcellular location of the carboxylase and enzymes involved in Vitamin K metabolism in rat liver

Carlisle¹,

Suttie²

1980

Biochemistry

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“…The accumulation of K 1 in the mitochondria in response to administration of labelled K 1 has been shown previously by sub‐cellular studies in rats . This increase led Thierry and Suttie to suggest a storage or metabolic role for mitochondria, therefore an outline of mitochondrial β‐oxidation is given in this review.…”

Section: Putative Phase‐i Transformationsmentioning

confidence: 64%

Vitamin K metabolism: Current knowledge and future research

Card

Górska

Cutler

et al. 2013

Molecular Nutrition Food Res

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Vitamin K is an essential fat-soluble micronutrient that is required for the post-translational γ-carboxylation of specific glutamic acid residues in hepatic and extra-hepatic proteins involved in blood coagulation and preventing cartilage and vasculature calcification. In humans, sources of vitamin K are derived from plants as phylloquinone and bacteria as the menaquinones. Menadione is a synthetic product used as a pharmaceutical but also represents an intermediate in the tissue-specific conversion of vitamin K to menaquinone-4, which preferentially resides in tissues such as brain. Research into vitamin K metabolism is essential for the understanding of vitamin K biology in health and disease. Progress in this area, driven by knowledge of vitamin K and the availability of markers of vitamin K status, has already proved beneficial in many areas of medicine and further opportunities present themselves. Areas of interest discussed in this review include prophylactic administration of vitamin K1 in term and preterm neonates, interactions between vitamins K and E, the industrial conversion of vitamin K to dihydro-vitamin K in foods, tissue-specific conversion of vitamin K to menaquinone-4, the biological activity of the five and seven carbon metabolites of vitamin K and circadian variations.

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“…While the presence or activity of organelle-specific marker proteins in each fraction can be readily determined, effective separation of subcellular compartments requires little overlap in protein markers between the fractions. Then the fractions can be subjected to chemical analysis of organelle associated compound accumulation by means of spectrophotometry, HPLC, − LC/MS, and most commonly, by scintillation counting of radiolabeled compounds. − …”

Section: Chemical Analysis As Evidence For Specific Organelle Accumul...mentioning

confidence: 99%

The Subcellular Distribution of Small Molecules: From Pharmacokinetics to Synthetic Biology

et al. 2011

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The systemic pharmacokinetics and pharmacodynamics of small molecules are determined by subcellular transport phenomena. Although approaches used to study the subcellular distribution of small molecules have gradually evolved over the past several decades, experimental analysis and prediction of cellular pharmacokinetics remains a challenge. In this article, we surveyed the progress of subcellular distribution research since the 1960s, with a focus on the advantages, disadvantages and limitations of the various experimental techniques. Critical review of the existing body of knowledge pointed to many opportunities to advance the rational design of organelle-targeted chemical agents. These opportunities include: 1) development of quantitative, nonfluorescence-based, whole cell methods and techniques to measure the subcellular distribution of chemical agents in multiple compartments; 2) exploratory experimentation with nonspecific transport probes that have not been enriched with putative, organelle-targeting features; 3) elaboration of hypothesis-driven, mechanistic and modeling-based approaches to guide experiments aimed at elucidating subcellular distribution and transport; and 4) introduction of revolutionary conceptual approaches borrowed from the field of synthetic biology combined with cutting edge experimental strategies. In our laboratory, state-of-the-art subcellular transport studies are now being aimed at understanding the formation of new intracellular membrane structures in response to drug therapy, exploring the function of drug-membrane complexes as intracellular drug depots, and synthesizing new organelles with extraordinary physical and chemical properties.

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Intracellular distribution of vitamin K in the rat

Cited by 23 publications

References 15 publications

Vitamin K dependent carboxylase: subcellular location of the carboxylase and enzymes involved in Vitamin K metabolism in rat liver

Vitamin K dependent carboxylase: subcellular location of the carboxylase and enzymes involved in Vitamin K metabolism in rat liver

Vitamin K metabolism: Current knowledge and future research

The Subcellular Distribution of Small Molecules: From Pharmacokinetics to Synthetic Biology

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