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- Table of Contents
Facts about [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial.
Inhibition of pyruvate dehydrogenase decreases glucose utilization and increases fat metabolism in response to prolonged fasting and starvation. Plays an important role in maintaining normal blood glucose levels under starvation, and is involved in the insulin signaling cascade.
Human | |
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Gene Name: | PDK4 |
Uniprot: | Q16654 |
Entrez: | 5166 |
Belongs to: |
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PDK/BCKDK protein kinase family |
[Pyruvate dehydrogenase [lipoamide]] kinase isozyme 4, mitochondrial; EC 2.7.11; EC 2.7.11.2; FLJ40832; Pyruvate dehydrogenase kinase isoform 4; pyruvate dehydrogenase kinase, isoenzyme 4; pyruvate dehydrogenase kinase, isozyme 4; pyruvate dehydrogenase, lipoamide, kinase isozyme 4, mitochondrial
Mass (kDA):
46.469 kDA
Human | |
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Location: | 7q21.3 |
Sequence: | 7; NC_000007.14 (95583499..95596516, complement) |
Ubiquitous; highest levels of expression in heart and skeletal muscle.
Mitochondrion matrix.
The PDK4 marker is part of the PDK/BCKDK protein kinase family. It helps in glycolytic metabolism, the increased utilization of fatty acid as an energy source, and lactate formation. In this article, we'll review the most effective applications of this marker in research. To learn more, continue reading! This article provides tips and tricks to help you optimize your experiments and discover the most effective control points.
The PDK4 gene regulates metabolic conversion from mitochondrial respiratory to cytoplasmic glucose, which is the preferred energy source for cancer cells. Located on chromosome 7q21.3 The gene has been implicated in a myriad of cellular processes. The PDK4 target miR-382-5p has recently been identified via bioinformatics analysis. Further clarification was made regarding the role played by this gene in NSCLC development.
To meet the high bioenergy demands of the liver metabolic reprogramming is required to be done in the context of liver renewal. The metabolic regulation has to be coordinated with liver growth. PDK4 regulates the metabolism glucose and fatty acids. It connects LR with fatty acid/glucose metabolic. It blocks the conversion of pyruvate to acetylCoA in regeneration. Additionally, it regulates fatty acid translocase Cd36, which improves the liver/body weight ratio mice that are WT. Additionally, PDK4 deficiencies inhibit the activity of AMPK.
PDK4 is a sensitive marker of metabolism that is activated when fatty acids are utilized as a fuel source. This gene is found in various tissues and metabolic adaption settings, including liver, heart muscle, kidneys, and the heart. The mRNA of PDK4 was elevated in tandem with fatty acids oxidation genes in all three. This suggests that the PDK4 gene could be a reliable marker in the detection of a metabolic switch from glucose to fatty acid.
Boster Bio's PDK4 marker enhances glycolysis by regulating mitochondrial function. The inhibition of PDK4 enhances glycolysis by blocking VSMCs from being calcified and mitochondria from fragmenting. This enzyme also promotes autophagy activity. We must first know how PDK4 regulates the cell's function before we can be able to understand how it functions. Here are a few examples.
PDK4 is a key player in the regulation of cellular energy and calcium homeostasis. It also modulates the integrity of the mitochondria-associated ER membrane, a structural link between the ER surface and the outer mitochondrial membrane. These two membranes play a crucial role in communication hubs for cell autophagy, energy homoeostasis and calcium homeostasis. The ER-mitochondrial connections are closely connected to the PDK4 regulation.
It is clear the function of PDK4 in tumor-specific treatments. It regulates a metabolic change that is linked to resistance to drugs. This pathway opens up new therapeutic options. This is why Boster Bio is developing a proprietary PDK4 marker to aid in cancer drug development. If you're interested in finding out more about how this marker facilitates glycolysis, you can contact Boster Bio.
PDK4 regulates mitochondrial respiration and lysosomal function. VSMCs with PDK4 knockdown improve the capacity of proliferative growth and also viability. It also inhibits LDHB, v-ATPase B1 and v-ATPase B1. Both of these are involved in mitochondrial respiration. Additionally, PDK4 blocks nuclear transfer of TFEB.
In muscle skeletal the expression of PDK4 is required to ensure optimal fat oxidation which results in a higher energy metabolism. The upstream transcription factor PGC-1a regulates PDK4. It is activated by the fatty acid-oxidation-promoting enzyme FOXO1, which promotes lipid oxidation. In addition, PDK4 inhibits the activity of pyruvate-dehydrogenase and facilitates increased fat utilization in the heart and skeletal muscles.
The PDK4 marker increases the production of lactate. Lactate levels were higher in cells that overexpress PDK4. Additionally cells' ATP levels were reduced in cells who express PDK4. These results suggest that the PDK4 gene facilitates the production of lactate in vivo. The precise mechanism behind lactate production is not known. The enzymes that regulate lactate biosynthesis are a bit ambiguous.
PDK4 downregulation results in an increase in ATP production and lactate production. This shift in metabolism happens during syncytialization. This process is also facilitated by other PDK isozymes such as cAMP. However, their quantity is much less. Downregulation of PDK4 is crucial for the proper functioning of syncytial functions.
The clinical significance of the PDK4 marker is strikingly significant. It is associated with hyperactive FASN in PCa, with a distinct dependence on OXPHOS. In vivo research is essential to investigate PDK4's action. However, the mechanisms through the PDK4 system regulate PCa aren't fully understood. The next step in the development of effective drugs to treat PCa involves identifying potential targets for treatment.
In vivo, PDK4 marker are able to increase the activity of HIF-1a/PKM2 enzymes. This is caused by activated oncogenes, HIF1a and PDK4 markers. It increases glycolytic enzyme activity and improves aerobic glucose metabolism. Lactate production increased when PDK4 was expressed in PC3 cells. However the knockdown of PDK4 resulted in a reduction in the production of lactate.
PMID: 8798399 by Rowles J., et al. Cloning and characterization of PDK4 on 7q21.3 encoding a fourth pyruvate dehydrogenase kinase isoenzyme in human.
PMID: 14966024 by Spriet L.L., et al. Pyruvate dehydrogenase activation and kinase expression in human skeletal muscle during fasting.
*More publications can be found for each product on its corresponding product page