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Energy Metabolism

$348
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunohistochemistry (Paraffin), Immunoprecipitation, Western Blotting

Background: AMP-activated protein kinase (AMPK) is highly conserved from yeast to plants and animals and plays a key role in the regulation of energy homeostasis (1). AMPK is a heterotrimeric complex composed of a catalytic α subunit and regulatory β and γ subunits, each of which is encoded by two or three distinct genes (α1, 2; β1, 2; γ1, 2, 3) (2). The kinase is activated by an elevated AMP/ATP ratio due to cellular and environmental stress, such as heat shock, hypoxia, and ischemia (1). The tumor suppressor LKB1, in association with accessory proteins STRAD and MO25, phosphorylates AMPKα at Thr172 in the activation loop, and this phosphorylation is required for AMPK activation (3-5). AMPKα is also phosphorylated at Thr258 and Ser485 (for α1; Ser491 for α2). The upstream kinase and the biological significance of these phosphorylation events have yet to be elucidated (6). The β1 subunit is post-translationally modified by myristoylation and multi-site phosphorylation including Ser24/25, Ser96, Ser101, Ser108, and Ser182 (6,7). Phosphorylation at Ser108 of the β1 subunit seems to be required for the activation of AMPK enzyme, while phosphorylation at Ser24/25 and Ser182 affects AMPK localization (7). Several mutations in AMPKγ subunits have been identified, most of which are located in the putative AMP/ATP binding sites (CBS or Bateman domains). Mutations at these sites lead to reduction of AMPK activity and cause glycogen accumulation in heart or skeletal muscle (1,2). Accumulating evidence indicates that AMPK not only regulates the metabolism of fatty acids and glycogen, but also modulates protein synthesis and cell growth through EF2 and TSC2/mTOR pathways, as well as blood flow via eNOS/nNOS (1).

$260
100 µl
APPLICATIONS
REACTIVITY
Hamster, Human, Monkey, Mouse, Rat

Application Methods: Immunofluorescence (Immunocytochemistry), Western Blotting

Background: β-galactosidase (also known as β-gal) is an essential hydrolase enzyme that catalyzes the hydrolysis of galactose-containing carbohydrates into monosaccharides. Substrates of β-galactosides include lactose, various glycoproteins, ganglioside GM1, and lactosylceramides. β-galactosidase is used widely in molecular biology; for example, isolation of recombinant bacteria during molecular cloning utilizes α-complementation of the bacterial β-galactosidase gene (lacZ) in the presence of a β-gal substrate to identify recombinant clones (1). In cell biology, Senescence-Associated beta-galactosidase (SA-β-gal), defined as β-gal activity at pH 6.0, is a widely used marker of replicative senescence. While initially thought to derive from a unique isoform of β-galactosidase expressed specifically in senescent cells (2), SA-β-gal activity was subsequently shown to result from overexpression and accumulation of β-galactosidase in endogenous lysosomes, and is not specifically required for replicative senescence (3).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: IDH2 is one of three isocitrate dehydrogenases (IDH1-3) that catalyze the oxidative decarboxylation of isocitrate to produce CO2 and α-ketoglutarate (α-KG). These enzymes belong to two distinct subclasses that utilize either NAD or NADP+ as an electron acceptor. IDH2 is an NADP+-dependent isocitrate dehydrogenase expressed primarily in the mitochondria, where it also functions in the TCA cycle (1,2). Mutations in IDH2 or its cytoplasmic counterpart (IDH1) have been reported in glioblastoma multiforme (3), acute myeloid leukemia (4,5), and other malignancies (6). Research studies have shown that gain-of-function mutations in IDH2 can lead to the accumulation and secretion of the oncometabolite R-2-hydroxyglutarate (2HG) in cancer cells (6,7).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: Cytochrome P450 2D6 (CYP2D6) is a member of the cytochrome P450 superfamily of enzymes. CYP2D6 is located in the endoplasmic reticulum where it oxidizes substrates such as drugs and environmental chemicals (1,2). CYP2D6 metabolizes more than 25% of current commonly used drugs including antidepressants, antipsychotics, analgesics, beta-adrenergic blocking agents, antiarrythmics, and antiemetics. The CYP2D6 gene is highly polymorphic in humans, resulting in phenotypes that vary from poor metabolizer to super metabolizer. A patient's CYP2D6 genotype was shown to be a good predictor of drug response and side effects and is thus used to guide treatments (3-5). Although abundantly expressed in liver, CYP2D6 is also expressed in other organs including brain. In brain, CYP2D6 and other CYP family members are expressed in a cell-specific, region-specific manner (6-8). CYP2D6 functions as a neuroprotective enzyme that increases with age and is induced by nicotine and alcohol (9,10).

$269
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Immunofluorescence (Immunocytochemistry), Immunohistochemistry (Paraffin), Immunoprecipitation, Western Blotting

Background: IDH2 is one of three isocitrate dehydrogenases (IDH1-3) that catalyze the oxidative decarboxylation of isocitrate to produce CO2 and α-ketoglutarate (α-KG). These enzymes belong to two distinct subclasses that utilize either NAD or NADP+ as an electron acceptor. IDH2 is an NADP+-dependent isocitrate dehydrogenase expressed primarily in the mitochondria, where it also functions in the TCA cycle (1,2). Mutations in IDH2 or its cytoplasmic counterpart (IDH1) have been reported in glioblastoma multiforme (3), acute myeloid leukemia (4,5), and other malignancies (6). Research studies have shown that gain-of-function mutations in IDH2 can lead to the accumulation and secretion of the oncometabolite R-2-hydroxyglutarate (2HG) in cancer cells (6,7).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Flow Cytometry, Immunofluorescence (Immunocytochemistry), Immunoprecipitation, Western Blotting

Background: Thymidine kinases play a critical role in generating the DNA synthetic precursor deoxythymidine triphosphate (dTTP) by catalyzing the phosphotransfer of phosphate from ATP to deoxythymidine (dT) and thymidine (T) in the cell. There are two known thymidine kinases, cytoplasmic thymidine kinase 1 (TK1) and mitochondrial thymidine kinase 2 (TK2) (1,2). Unlike TK2, which is not modulated by the cell cycle, TK1 expression and activity is regulated in a cell cycle-dependent manner, accumulating during G1-phase to peak levels in S-phase before being degraded prior to cell division (3,4). Stability, but not activity, may be regulated via phosphorylation of TK1 at Ser13 by Cdc2 and/or Cdk2, but the precise mode of regulation remains elusive (5). These observations indicate that TK1 might be a useful marker of cell proliferation; however, recent studies have shown that TK1 plays a more significant role in the DNA damage response (6). Genotoxic stress promotes increased TK1 expression and kinase activity resulting in reduced cellular apoptosis and enhanced DNA repair efficiency (6). More importantly, numerous studies show that TK1 expression and activity are upregulated during neoplasia and disease progression in humans, and increased serum levels of TK1 correlate with poor prognosis and decreased survival in patients with various types of advanced tumors (7-12).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Western Blotting

Background: Cystathionine beta-synthase (CBS) is a key enzyme involved in sulfur amino acid metabolism because it catalyzes the formation of cystathionine from serine and homocysteine (1,2). The CBS protein contains a heme-binding domain that modulates enzyme activity by sensing redox changes or carbon monoxide binding (1). S-adenosylmethionine binds the carboxyl-terminal CBS domain to allosterically regulate CBS catalytic activity (3,4). In addition to catalyzing cystathionine formation, CBS also catalyzes the generation of hydrogen sulfide, a neuromodulator in the brain, through alternative reactions (5,6). Mutations in the corresponding CBS gene result in homocystinuria, an autosomal recessive disorder characterized by abnormal sulfur metabolism, mental retardation, eye anomalies, and vascular disease (7).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: The 1-acylglycerol-3-phosphate-O-acyltransferase 2 enzyme (AGPAT2) catalyzes the acylation of lysophosphatidic acid (LPA) into phosphatidic acid (PA), which is a precursor for the synthesis of triacylglycerol and phospholipid (1,2). AGPAT2 is highly expressed in adipose tissues, liver, and skeletal muscle (3). The induced knockdown of AGPAT2 expression results in decreased expression of adipogenic proteins and delayed expression of adipogenic marker proteins, suggesting that AGPAT2 plays an important role in adipocyte growth and differentiation (4). Mutations in the corresponding AGPAT2 gene cause autosomal recessive congenital generalized lipodystrophy type 1 (CGL1), also described as Berardinelli-Seip syndrome. Patients with CGL1 are born without detectable white adipose tissue and tend to develop severe insulin resistance, hypertriglyceridemia, and type 2 diabetes during childhood (5,6).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: NADP+ dependent methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) is a mitochondrial enzyme that catalyzes the production of formate from 10-formyl-tetrahydrofolate, the last step in one-carbon (1-C) flow from mitochondria to cytoplasm (1,2). These one-carbon end products are required for de novo synthesis of thymidylate and purines. In the mitochondria, these essential one-carbon products are formed by a series of reactions catalyzed by a pair of enzymes (MTHFD2 and MTHFD1L), but by the trifunctional MTHFD1 enzyme in the cytoplasm (3). The 10-formyl-tetrahydrofolate synthetase MTHFD1L is widely expressed in most adult tissues and at all stages of mammalian embryonic development (1). Research studies using MTHFD1L knockout mice indicate that MTHFD1L plays an essential role in neural tube formation; mice lacking MTHFD1L displayed neural tube and craniofacial defects leading to embryonic lethality (4).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse

Application Methods: Western Blotting

Background: NADP+ dependent methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) is a mitochondrial enzyme that catalyzes the production of formate from 10-formyl-tetrahydrofolate, the last step in one-carbon (1-C) flow from mitochondria to cytoplasm (1,2). These one-carbon end products are required for de novo synthesis of thymidylate and purines. In the mitochondria, these essential one-carbon products are formed by a series of reactions catalyzed by a pair of enzymes (MTHFD2 and MTHFD1L), but by the trifunctional MTHFD1 enzyme in the cytoplasm (3). The 10-formyl-tetrahydrofolate synthetase MTHFD1L is widely expressed in most adult tissues and at all stages of mammalian embryonic development (1). Research studies using MTHFD1L knockout mice indicate that MTHFD1L plays an essential role in neural tube formation; mice lacking MTHFD1L displayed neural tube and craniofacial defects leading to embryonic lethality (4).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunofluorescence (Immunocytochemistry)

Background: Mammalian cells synthesize serine de novo by diverting a portion of the glycolytic intermediate 3-phosphoglycerate into the phosphorylated pathway of serine synthesis. This shift supports anabolism by providing precursors for the biosynthesis of proteins, nucleotides, creatine, porphyrins, phospholipids, and glutathione. Phosphoglycerate dehydrogenase (PHGDH) catalyzes the first step in the serine biosynthesis pathway by converting 3-phosphoglycerate into phosphohydroxy pyruvate (1).Research studies demonstrate that an increase in serine biosynthesis supports growth and proliferation of cancer cells (2-4), which is supported by amplification and overexpression of PHGDH in a subset of melanoma and breast cancers (5,6). Suppression of PHGDH expression in cell lines with elevated PHGDH levels causes a strong decrease in cell proliferation and inhibits tumor growth in vivo (5). Additional evidence suggests that PHGDH interacts with and stabilizes FoxM1, which promotes the proliferation, invasion, and tumorigenicity of glioma cells (7).

$122
20 µl
$293
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse

Application Methods: Immunohistochemistry (Paraffin), Immunoprecipitation, Western Blotting

Background: ABCG2 (BCRP1/ABCP/MXR) is a member of the ATP-binding cassette transporter family that functions as ATP-dependent transporters for a wide variety of chemical compounds and are associated with drug-resistance in cancer cells (1-6). ABCG2 is a heavily glycosylated transmembrane protein with six transmembrane spanning regions consistent with it functioning as a half-transporter. The ABC family can exist as either full-length transporters or as half-transporters that form functional transporters through homo- or heterodimerization. High expression of ABCG2 was found in placenta as well as cell lines selected for resistance to a number of chemotherapeutic drugs, including mitoxantrone, doxorubicin, topotecan and flavopiridol. In rodents, the highest expression of ABCG2 was found in kidney (8). ABCG2 expression has also been observed in stem cell populations, particularly in hematopoietic and neuronal stem cells and is downregulated with differentiation (9-12).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: Nicotinamide phosphoribosyltransferase (NAMPT; also known as Pre-B cell-enhancing factor PBEF) catalyzes the synthesis of nicotinamide mononucleotide (NMN) from nicotinamide and 5-phosphoribosylpyrophosphate (PRPP), the rate-limiting step in the NAD biosynthesis pathway starting from nicotinamide (1,2). NAD biosynthesis mediated by NAMPT plays a critical role in glucose-stimulated insulin secretion in pancreatic beta cells (3). Both NAMPT inhibitors and activators have been sought for clinical applications (4,5). NAMPT has intra- and extracellular forms (iNAMPT and eNAMPT), and deacetylation of iNAMPT by SIRT1 promotes eNAMPT secretion through a nonclassical secretory pathway (3,6). eNAMPT, independent of its enzymatic activity, can induce epithelial-to-mesenchymal transition in mammary epithelial cells and promote monocyte differentiation into a tumor-supporting M2 macrophage (7,8).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: Mammalian cells synthesize serine de novo by diverting a portion of the glycolytic intermediate 3-phosphoglycerate into the phosphorylated pathway of serine synthesis. This shift supports anabolism by providing precursors for the biosynthesis of proteins, nucleotides, creatine, porphyrins, phospholipids, and glutathione. Phosphoglycerate dehydrogenase (PHGDH) catalyzes the first step in the serine biosynthesis pathway by converting 3-phosphoglycerate into phosphohydroxy pyruvate (1).Research studies demonstrate that an increase in serine biosynthesis supports growth and proliferation of cancer cells (2-4), which is supported by amplification and overexpression of PHGDH in a subset of melanoma and breast cancers (5,6). Suppression of PHGDH expression in cell lines with elevated PHGDH levels causes a strong decrease in cell proliferation and inhibits tumor growth in vivo (5). Additional evidence suggests that PHGDH interacts with and stabilizes FoxM1, which promotes the proliferation, invasion, and tumorigenicity of glioma cells (7).

$293
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunofluorescence (Immunocytochemistry), Immunohistochemistry (Paraffin), Immunoprecipitation, Western Blotting

Background: Argininosuccinate synthetase (ASS1) catalyzes the formation of argininosuccinate from citrulline and aspartate, the rate-limiting step in the urea cycle that is responsible for the synthesis of arginine and the clearance of nitrogenous waste (1). ASS1 is ubiquitously and differentially expressed in different cell types and tissues. Mutations in ASS1 are associated with citrullinemia type I, an autosomal recessive disease characterized primarily by elevated serum and urine citrulline levels in human patients (2, 3).Loss of ASS1 expression is one of the common metabolic alterations observed in many cancers, and it is a prognostic biomarker of reduced metastasis-free survival. ASS1 deficiency leads to the dependence of extracellular arginine for survival, proliferation, and cell growth. Ariginine starvation induces autophagy and apoptosis in ASS1 deficient cells and this has been exploited as a therapeutic intervention for the tumors with loss of ASS1 expression (4, 5). Pegylated arginine deiminase (ADI-PEG20), an enzyme that degrades arginine into citrulline, causes significant growth inhibition in tumors that have lost ASS1 expression, such as hepatocellular carcinoma, breast cancer, and sarcoma (6-8).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: Nicotinamide phosphoribosyltransferase (NAMPT; also known as Pre-B cell-enhancing factor PBEF) catalyzes the synthesis of nicotinamide mononucleotide (NMN) from nicotinamide and 5-phosphoribosylpyrophosphate (PRPP), the rate-limiting step in the NAD biosynthesis pathway starting from nicotinamide (1,2). NAD biosynthesis mediated by NAMPT plays a critical role in glucose-stimulated insulin secretion in pancreatic beta cells (3). Both NAMPT inhibitors and activators have been sought for clinical applications (4,5). NAMPT has intra- and extracellular forms (iNAMPT and eNAMPT), and deacetylation of iNAMPT by SIRT1 promotes eNAMPT secretion through a nonclassical secretory pathway (3,6). eNAMPT, independent of its enzymatic activity, can induce epithelial-to-mesenchymal transition in mammary epithelial cells and promote monocyte differentiation into a tumor-supporting M2 macrophage (7,8).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: Insulin receptor substrate 1 (IRS-1) is one of the major substrates of the insulin receptor kinase (1). IRS-1 contains multiple tyrosine phosphorylation motifs that serve as docking sites for SH2-domain containing proteins that mediate the metabolic and growth-promoting functions of insulin (2-4). IRS-1 also contains over 30 potential serine/threonine phosphorylation sites. Ser307 of IRS-1 is phosphorylated by JNK (5) and IKK (6) while Ser789 is phosphorylated by SIK-2, a member of the AMPK family (7). The PKC and mTOR pathways mediate phosphorylation of IRS-1 at Ser612 and Ser636/639, respectively (8,9). Phosphorylation of IRS-1 at Ser1101 is mediated by PKCθ and results in an inhibition of insulin signaling in the cell, suggesting a potential mechanism for insulin resistance in some models of obesity (10).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: Nicotinamide mononucleotide adenylyl transferases (NMNATs) catalyze the reversible reaction of ATP with NaMN (nicotinic acid mononucleotide) or NMN (nicotinamide mononucleotide) to produce NaAD (nicotinic acid adenine dinucleotide) or NAD (nicotinamide adenine dinucleotide). NAD is an essential cofactor or substrates for many enzymes like PARP1 and Sirt1 that regulate diverse cellular processes including oxidative reactions and transcription. NMNATs maintain NAD levels for internal homeostasis (1,2). NMNAT1 is localized to the nucleus and loss-of-function mutant in mice causes embryonic lethality (3). In humans, several different NMNAT1 mutations are associated with Leber congenital amaurosis (LCA), the most common cause of inherited childhood blindness (4-7).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: The multidrug resistance-associated protein 6 (MRP6, ABCC6) is a member of ATP-binding cassette (ABC) family transporters that move drugs and hydrophobic compounds across cell membranes. The MRP6 protein is expressed mainly in liver and kidney, and in other tissues to a lesser extent (1). Identified MRP6 substrates include the glutathione conjugate of N-ethylmaleimide (NEM-GS) and leukotriene C4 (LTC4), with more tentative MRP6 substrates under investigation (2,3). Research studies show that increased MRP6 expression correlates with induced cholesterol biosynthesis, which suggests that MRP6 may be involved in lipid and cholesterol homeostasis (4). A small isoform of MRP6 is up-regulated in HBV infected hepatocytes and protects the cells from apoptosis mediated by caspase 3 and caspase 8 (5,6). Mutations in the corresponding ABCC6 gene cause pseudoxanthoma elasticum (PXE), an autosomal recessive disorder that is characterized by the accumulation of mineralized and fragmented elastic fibers in the skin, eyes, and arteries (7,8). Mutations in ABCC6 also result in generalized arterial calcification of infancy, an ectopic calcification disease that lies along a spectrum of similar disorders with PXE (9).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: Iron regulatory proteins (IRPs; also known as IREBs) are RNA-binding proteins that recognize iron-responsive elements (IREs) and play an important role in maintaining iron homeostasis in mammalian cells. IREs are conserved cis-regulatory hairpin structures located within the 5’ or 3’ untranslated regions (UTRs) of target mRNAs. IRPs inhibit translation when bound to IREs within the 5’ UTR of mRNA encoding for proteins involved in iron storage, export, and utilization. IRP binding to multiple IREs within the 3’ UTR of transferin receptor 1 (TFR1) mRNA prevents its degradation, thereby augmenting translation of TFR1 and increasing iron uptake into cells (1-3). Dysregulation of IRPs has been associated with human cancers (4-6).