PC

What is PC Protein?

Pyruvate Carboxylase, or PC, is an enzyme loaded with biotin that has the important task of converting pyruvate into oxaloacetate. This reaction helps refill oxaloacetate levels when they drop during the TCA cycle, ensuring that many essential biochemical processes continue to function well. PC is a major player in metabolism, managing how energy is steered towards creating glucose, generating fats, and releasing insulin. It’s got some tissue-specific roles too; in the liver and kidneys, PC is essential for glucose production, while in fat tissues and the liver, it aids in building fats.

What is the Function of PC Protein?

Pyruvate Carboxylase, or PC, is an enzyme that's key in metabolism. It helps change pyruvate into oxaloacetate, which is essential for maintaining enough oxaloacetate levels when they're depleted in the TCA cycle. This ensures that the important energy production process keeps running smoothly. PC is involved in several metabolic pathways like gluconeogenesis, where it helps produce glucose, and lipogenesis, which is key in creating fatty acids. Its action is particularly significant in tissues like the liver, which manages blood sugar levels, and in fat tissues that store energy.

PC Related Signaling Pathway

Pyruvate Carboxylase (PC) is a pivotal part of several metabolic pathways, acting especially within the gluconeogenesis process where it facilitates the formation of glucose from other substrates. It ensures there's a steady supply of the TCA cycle intermediates, essential for energy production. PC also engages in lipogenesis, helping synthesize fatty acids. Key signaling pathways associated with PC include those linked to energy balance and metabolic control, such as responding to insulin levels and influencing glucose and lipid metabolism. Its function is crucial in tissues like the liver and adipose tissue, where it supports different biosynthetic processes.

PC Related Diseases

Pyruvate Carboxylase (PC) deficiency is a genetic disorder affecting metabolism and energy production. This condition leads to the accumulation of lactic acid and other toxins, severely impacting the body's organs and tissues, especially the nervous system. There are three main types: Type A mainly affects infants in North America, causing developmental delays and serious symptoms; Type B, found mostly in Europe, presents life-threatening symptoms shortly after birth; and the milder Type C shows minimal neurological impacts. The disorder is rare, often appearing in certain genetic populations, like some Canadian Algonkian tribes, with the PC gene mutation responsible for reducing the enzyme activity necessary for crucial metabolic pathways.

Bioapplications of PC

Pyruvate Carboxylase (PC) is widely studied in fields like biochemistry and medical research due to its essential role in metabolic pathways. In the lab, researchers explore PC to better understand energy metabolism and metabolic disorders, making it valuable in studies related to diabetes and obesity. In industry, PC can be applied in fermentation processes to enhance the production of amino acids and other compounds. Clinically, there's interest in targeting PC for therapies to manage metabolic diseases and for crafting strategies to address enzyme deficiencies. Its function in converting pyruvate to oxaloacetate, an important step in gluconeogenesis, makes PC a key player in bioengineering efforts aiming to manipulate metabolic flows in synthetic biology and other applications.

Case Study 1: Schwörer S. et al. Nat Metab. 2021

Collagen overproduction by fibroblasts is key in solid tumors and impacts cancer growth. Despite limited glutamine and glucose supply, mesenchymal cells keep making extracellular matrix proteins. This study reveals pyruvate carboxylase (PC) in fibroblasts supports tumor fibrosis and growth. Using cell cultures and mouse models, they showed extracellular lactate helps maintain the TCA cycle and amino acid production. PC activity is vital for collagen creation in tumors, suggesting it as a target to reduce tumor desmoplasia.

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  Fig1. PC activity after [1-13C] Lac tracing in NIH-3T3 cells.
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  Fig2. Western Blot of NIH-3T3 cells expressing Ctrl or PC sgRNA, treated with CB839 for 48h.

Case Study 2: Phannasil P. et al. PLoS One. 2015

Researchers discovered that pyruvate carboxylase (PC) is key for the tricarboxylic acid cycle in cells, especially in replenishing intermediates for biosynthesis. In a study with 57 breast cancer patients, they found that PC levels were higher in cancerous tissues and correlated with tumor size and stage (P < 0.05). Further, they examined four breast cancer cell lines and found that those with higher metastasis potential showed 2-3 times more PC. By reducing PC in aggressive lines, they cut cell proliferation and invasion by half, while increasing PC in less aggressive cells doubled these capabilities.

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  Fig3. Western blot analysis of PC protein in the above cell lines.
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  Fig4. Proliferation rate of MCF-7 cells overexpressing PC grown in the medium containing 4 mM glutamine.

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  Fig1. Pathways regulated by PC in cancer. (Violet A Kiesel, 2021)
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  Fig2. Regulation of PC in cancer cells. (Violet A Kiesel, 2021)

PC has several biochemical functions, for example, ATP binding,DNA binding,biotin binding. Some of the functions are cooperated with other proteins, some of the functions could acted by PC itself. We selected most functions PC had, and list some proteins which have the same functions with PC. You can find most of the proteins on our site.

Function	Related Protein
pyruvate carboxylase activity	PCXA,PCXB
protein binding	TRAF1,MPDZ,NOSIP,TMEM25,CSNK1G2,RPS27,KISS1,C17orf82,NFKBIZ,ABL1
DNA binding	ZNF18,ZIC5,ZNF423,ARID3C,RAG1,ZNF182,CDKN2A,FOXB1A,ZBTB16A,KDM5BA
ATP binding	ATP1A3,STK16,RPS6KA3A,STK24A,SUPV3L1,STK38A,ATP6V1A,ATAD1,RFC2,NLRP4E
biotin binding	PCXB,AVR2,PCXA,HLCS,PCCA,MCCC1
biotin carboxylase activity	MCCC1,PCXB,ACACB,PCCA,ACACA,PCXA
metal ion binding	S100A10B,YY1B,Itgam&Itgb2,ATP2C1,ACAT1,ZNF606,PAN3,TIPARP,CYP4A12A,PDZRN3B

PC has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with PC here. Most of them are supplied by our site. Hope this information will be useful for your research of PC.

q03463-pro_0000278740;PPP2R2B;q99ib8-pro_0000045602;Ckap5;polg_hcvjf_rna;XRCC3;ERBB2;IFIT1;RAB7A;DYNLL1;Tubg1