The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Up-Regulation of Carnitine Transporters Helps Maintain Tissue Carnitine Levels in Carnitine Deficiency Induced by Pivalic Acid
Abstract
Purpose Pivalic acid (PVA) forms conjugates with endogenous carnitine and enhances its excretion. The purpose of this study is to determine whether tissue carnitine levels decrease in parallel with plasma levels in carnitine deficiency induced by PVA.Methods PVA was orally administered to rats for 5 days. Carnitine levels in plasma, liver, kidney, muscle, and heart were monitored. The tissue uptake clearance (CLuptake) was determined in vivo by the integration plot method. Hepatocytes were prepared from control and PVA-treated rats, and the uptake of L-carnitine was determined.Results Plasma concentrations of L-carnitine decreased as a result of the enhanced carnitine elimination as pivaloylcarnitine (PCN) when rats were treated with PVA. However, L-carnitine concentrations in liver, muscle, and heart remained relatively constant during the study. period. CLuptake increased in liver and muscle and, thus, the rate of carnitine uptake from plasma into these tissues did not change even at low plasma concentrations. This helps maintain carnitine levels in these tissues. Up-regulation of carnitine transporters is suggested to be a mechanism for the increased CLuptake.Conclusions In the carnitine deficiency state induced by PVA, increased CLuptake owing to up-regulation of carnitine transporters is suggested to help maintain carnitine levels in some tissues.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Other clinical factors that disrupt carnitine status include renal dysfunction and use of drugs that form carnitine conjugates (32,33).”
From Carnitine insufficiency caused by aging and overnutrition compromises mitochondrial performance and metabolic control (2009) · cites this paper as [32]
Citations
Cites
Tamai, I., Ohashi, R., Nezu, J., Yabuuchi, H., Oku, A., Shimane, M., Sai, Y., & Tsuji, A. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.32.20378 · Cited by 696
Nezu, J., Tamai, I., Oku, A., Ohashi, R., Yabuuchi, H., Hashimoto, N., Nikaido, H., Sai, Y., Koizumi, A., Shoji, Y., et al. (1999) · Nature Genetics · doi:10.1038/5030 · Cited by 553
Wu, X., Huang, W. Y., Prasad, P. D., Seth, P., Rajan, D. P., Leibach, F. H., Chen, J., Conway, S. J., & Ganapathy, V. (1999) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)35056-6 · Cited by 330
CARNITINE DEFICIENCY INDUCED BY PIVAMPICILLIN AND PIVMECILLINAM THERAPY
Holme, E., Jacobson, C.-E., Nordin, I., Greter, J., Lindstedt, S., KRISTIANSSON, B., & Jodal, U. (1989) · The Lancet · doi:10.1016/s0140-6736(89)92086-2 · Cited by 170
Yamazaki, M., Suzuki, H., Hanano, M., Tokui, T., Komai, T., & Sugiyama, Y. (1993) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1993.264.1.g36 · Cited by 152
Self-citationTurnover of carnitine by rat tissues
Brooks, D. E., & McIntosh, J. E. A. (1975) · Biochemical Journal · doi:10.1042/bj1480439 · Cited by 124
Carnitine movement across muscle cell membranes. Studies in isolated rat muscle
Rebouche, C. J. (1977) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(77)90402-3 · Cited by 119
Molecular Cloning and Characterization of High-Affinity Carnitine Transporter from Rat Intestine
Sekine, T., Kusuhara, H., Utsunomiya‐Tate, N., Tsuda, M., Sugiyama, Y., Kanai, Y., & Endou, H. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9521 · Cited by 102
Self-citationPivampicillin-promoted excretion of pivaloylcarnitine in humans
Melegh, B., Kerner, J., & BIEBER, L. L. (1987) · Biochemical Pharmacology · doi:10.1016/0006-2952(87)90318-2 · Cited by 101
Longo, A., Bruno, G. A., Curti, S., et al. (1996) · Journal of Chromatography B Biomedical Sciences and Applications · doi:10.1016/s0378-4347(96)00219-8 · Cited by 69
Research works printed but not linked: 2
- R. Fujii, K. Sunakawa, T. Yokota, Y. Nitta, H. Akita, S. Iwata, Y. Satoh, H. Meguro, H. Satoh, K. Niino, Y. Toyonaga, N. Iwai, H. Nakamura, Y. Kobayashi, M. Kino, H. Higashino, H. Kamiya, K. Kitamura, M. Ito, T. Nishikawa, H. Tada, A. Maruo, and S. Yamamoto. Safety and carnitine status after oral administration of S-1108 to pediatric patients. Chemotherapy 41:655-665 (1993).
- Y. Sawada. Physiological parameters in humans and animals. In M. Hanano, K. Umemura, and T. Iga (eds.), Applied Pharmacokinetics—Theory and Experiments, Soft Science, Inc., Tokyo, Japan, 1985 pp. 433-449.
Cited by
Sorted by citations
Noland, R. C., Koves, T. R., Seiler, S. E., Lum, H., Lust, R. M., Ilkayeva, O., Stevens, R. D., Hegardt, F. G., & Muoio, D. M. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.032888 · Cited by 317
Metadata
- Authors
- Okudaira, N., Fujigaki, M., Nakayoshi, T., Komiya, I., & Sugiyama, Y.
- Affiliations
- Meiji Seika Pharma Co., Ltd. (Japan) (JP)
- The University of Tokyo (JP)
- Corresponding author
- Okudaira, Noriko
- Venue
- Pharmaceutical Research
- Published
- 2001-04
- Volume
- 18
- Issue
- 4
- Pages
- 439-445
- ISSN
- 0724-8741 (ISSN-L)
- 1573-904X
- OpenAlex
- W1499536514
- Cited by
- 8
- References
- 29
- Citations by year
- 2016: 1 · 2014: 1 · 2013: 1
- FWCI
- 0.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Pharmaceutical Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- carnitine deficiency, pivalic acid, carnitine transporter, L-carnitine, plasma carnitine
- MeSH terms
- Solute Carrier Family 22 Member 5, Animals, Carnitine, Carrier Proteins, Injections, Intra-Arterial, Injections, Intravenous, Male, Pentanoic Acids, Tissue Distribution, Up-Regulation, Rats, Sprague-Dawley, Organic Cation Transport Proteins, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Up-Regulation of Carnitine Transporters Helps Maintain Tissue Carnitine Levels in Carnitine Deficiency Induced by Pivalic Acid. https://app.cochat.ai/papers/10.1023/a:1011042008169
- The paper
- Okudaira, N., Fujigaki, M., Nakayoshi, T., Komiya, I., & Sugiyama, Y. (2001). Up-Regulation of Carnitine Transporters Helps Maintain Tissue Carnitine Levels in Carnitine Deficiency Induced by Pivalic Acid. Pharmaceutical Research. https://doi.org/10.1023/a%3A1011042008169
