Article: Metabolic enzyme pyruvate kinase M2 regulates platelet function and arterial thrombosis Authors: Manasa K Nayak, Madankumar Ghatge, Gagan D Flora, Nirav Dhanesha, Manish Jain, Kathleen R Markan, Matthew J Potthoff, Steven R Lentz, Anil K Chauhan Journal: Blood. 2020 Oct 7;blood.2020007140. doi: 10.1182/blood.2020007140. Online ahead of print. Abstract:Very little is known about the role…
Approach and Results-We identified a large number of JmjC domain-containing proteins regulated by endothelial differentiation of murine embryonic stem cells. Among the family of JmjC domain-only proteins, Jmjd8 was significantly upregulated on endothelial differentiation. Knockdown of Jmjd8 in ECs significantly decreased in vitro network formation and sprouting in the spheroid assay. JMJD8 is exclusively detectable in the cytoplasm, excluding a function as a histone-modifying enzyme. Mass spectrometry analysis revealed JMJD8-interacting proteins with known functions in cellular metabolism like pyruvate kinase M2. Accordingly, knockdown of pyruvate kinase M2 in human umbilical vein ECs decreased endothelial sprouting in the spheroid assay. Knockdown of JMJD8 caused a reduction of EC metabolism as measured by Seahorse Bioscience extracellular flux analysis. Conversely, overexpression of JMJD8 enhanced cellular oxygen consumption rate of ECs, reflecting an increased mitochondrial respiration. ...
Urs Giger. Anemia is one of the most common clinical signs and abnormal laboratory test results in companion animals. Although acquired conditions such as infections, immune disorders, intoxications, blood loss and chronic organ failures represent the main causes of anemia, hereditary blood diseases leading to anemia are also important in clinical practice. Several hereditary erythrocyte defects have been reported in cats and a molecular basis of the erythrocyte pyruvate kinase defect has recently been determined.. Pyruvate kinase is a key regulatory enzyme in the metabolism of sugar. Its deficiency leads to a lack of energy production and thus, an instability of erythrocyte blood cells. This will then result in anemia. PK deficient cats typically have intermittent anemia. The age of onset is quite variable and may depend on environmental factors. The youngest affected cat diagnosed with anemia was 6 months of age and the oldest affected cat was 12 years old and was only found based on screening ...
Mitapivat showed positive safety and efficacy outcomes in patients with pyruvate kinase deficiency who were not regularly receiving red cell transfusions.
A deficiency in the enzyme Pyruvate Kinase impairs the red blood cells ability to metabolize, which in turn may cause anemia and other blood-related issues. Breeds more prone to this deficiency include the Abyssinian, Somali, and domestic shorthair cats. Learn more about the causes and treatment of this condition in cats on PetMD.com.
Intact rats trained on a controlled feeding and lighting schedule designated 8+16 exhibited diurnal oscillations in liver weight, glucokinase activity and liver glycogen content. Glucokinase activity expressed as units/g of liver decreased to 30% of that from unoperated controls during the first 48h after partial hepatectomy and returned to near normal values in 2 weeks. When the glucokinase activity was expressed as units/liver per 100g body wt., a decrease to 50% of control activity was observed between 24 and 48h after the operation. A similar pattern was found for pyruvate kinase type I. In contrast, pyruvate kinase type III activity increased after partial hepatectomy. It is suggested that the newly divided cells after partial hepatectomy do not synthesize glucokinase and pyruvate kinase I but do synthesize pyruvate kinase III. Glycogen was found to accumulate as early as 24h after partial hepatectomy, and normal concentrations were reached after 48h if the operation was performed at ...
Pyruvate kinase is the enzyme that catalyzes the final step of glycolysis. It catalyzes the transfer of a phosphate group from phosphoenolpyruvate (PEP) to adenosine diphosphate (ADP), yielding one molecule of pyruvate and one molecule of ATP. Pyruvate kinase is present in four distinct, tissue-specific isozymes in animals, each consisting of particular kinetic properties necessary to accommodate the variations in metabolic requirements of diverse tissues. There are four isozymes of pyruvate kinase in vertebrates: L (liver), R (erythrocytes), M1(muscles, hearts and brain) and M2 (only form detectable in early fetal tissue and present in most adult tissues). R and L isozymes differ from M1 and M2 in that they are both exclusively allosterically and reversibly regulated. From a kinetic standpoint, the R and L isozymes of pyruvate kinase have two key conformation states; one with a high substrate affinity and one with a low substrate affinity. The R-state, characterized by high substrate affinity, ...
Macrophages activated by the TLR4 agonist LPS undergo dramatic changes in their metabolic activity. We here show that LPS induces expression of the key metabolic regulator Pyruvate Kinase M2 (PKM2). Activation of PKM2 using two well-characterized small molecules, DASA-58 and TEPP-46, inhibited LPS-induced Hif-1α and IL-1β, as well as the expression of a range of other Hif-1α-dependent genes. Activation of PKM2 attenuated an LPS-induced proinflammatory M1 macrophage phenotype while promoting traits typical of an M2 macrophage. We show that LPS-induced PKM2 enters into a complex with Hif-1α, which can directly bind to the IL-1β promoter, an event that is inhibited by activation of PKM2. Both compounds inhibited LPS-induced glycolytic reprogramming and succinate production. Finally, activation of PKM2 by TEPP-46 in vivo inhibited LPS and Salmonella typhimurium-induced IL-1β production, while boosting production of IL-10. PKM2 is therefore a critical determinant of macrophage activation by ...
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Different pyruvate kinase isoforms are expressed in a tissue-specific manner, with pyruvate kinase M2 (PKM2) suggested to be the predominant isoform in proliferating cells and cancer cells. Due to differential regulation of enzymatic activities, PKM2 but not PKM1 has been thought to favor cell proliferation. However, the role of PKM2 in tumorigenesis has been recently challenged. Here we report that increased glucose catabolism through glycolysis and increased pyruvate kinase activity in c-MYC-driven liver tumors are associated with increased expression of both PKM1 and PKM2 isoforms and decreased expression of the liver-specific isoform of pyruvate kinase, PKL. Depletion of PKM2 at the time of c-MYC over-expression in murine livers did not affect c-MYC induced tumorigenesis and resulted in liver tumor formation with decreased pyruvate kinase activity and decreased catabolism of glucose into alanine and the Krebs cycle. An increased PKM1/PKM2 ratio by ectopic PKM1 expression further decreased ...
What is the subunit composition? Larsen, T. M., L. T. Laughlin, H. M. Holden, L. Rayment, G. H. Reed. 1994. Structure of rabbit muscle pyruvate kinase complexed with Mn2+, K+, and pyruvate. Biochemistry 33:6301-6309.. ...
Abstract: Together with an increase in the total activity of pyruvate kinase, alterations in the isoenzyme spectrum were observed in hepatocarcinogenesis caused by treatment of rats with diethylinitrosamine. The alterations might be divided into two steps: initial, reversible changes and changes immediately related to development of the blastomatous process. The total activity of pyruvate kinase was gradually increased with appearance of hyperplastic symptoms as well as of primary tumoral foci in liver tissue. The M2-type of pyruvate kinase tended to exhibit activation. In primary hepatomas the L-type of the enzyme was decreased and activity of the M2-type was increased ...
Emerging studies have identified microRNAs as possible therapeutic tools for the treatment of glioma, the most aggressive brain tumor. Their important targets in this tumor are not well understood. We recently found that the Notch pathway is a target of microRNA-326. Ectopic expression of microRNA-326 in glioma and glioma stem cells induced their apoptosis and reduced their metabolic activity. Computational target gene prediction revealed pyruvate kinase type M2 (PKM2) as another target of microRNA-326. PKM2 has recently been shown to play a key role in cancer cell metabolism. To investigate whether it might be a functionally important target of miR-326, we used RNA interference to knock down PKM2 expression in glioma cells. Transfection of established glioma and glioma stem cells with PKM2 siRNA reduced their growth, cellular invasion, metabolic activity with decreased ATP and glutathione levels, and activated AMP-activated protein kinase. The cytotoxic effects exhibited by PKM2 knockdown in ...
Although multiple available siRNA design algorithms did not predict any sequences within alternative exon 10 that would mediate robust silencing, we have identified multiple siRNAs that afford potent and specific silencing of the M2 isoform of pyruvate kinase. An inspection of the 10 top performing sequences reveals that the number of mismatches between the M1 and M2 isoforms ranges from 4 to 13. 5 of these 10 sequences contain mismatches at one of the critical central positions 10 or 11, which have been shown to be important in conferring specificity (Wang et al., 2008b). We observed one "hot spot": two of the top three siRNAs target consecutive 19-mers (si155 and si156). We also observed one "warm spot": three siRNAs work moderately well over a sequence that spans 23 nucleotides (si83, si85, and si87).. Recent analysis of transcriptomes indicates that ,90% of all human genes are expressed as alternatively spliced isoforms (Wang et al., 2008a). The ability to target one isoform of a gene ...
The enzyme activities and isozyme distribution of the three glycolytic regulator enzymes hexokinase, phosphofructokinase and pyruvate kinase were studied in lymphocytes of patients with chronic lymphocytic leukemia. Isozyme distribution patterns were determined by kinetic measurements, electrophoresis and immunoprecipitation. The CLL lymphocytes were different from normal non-T lymphocytes with respect to hexokinase ... read more residual activity in the presence of glucose-1,6-P2, pyruvate kinase residual activity in the presence of alanine, and phosphofructokinase activity after stimulation by glucose-1,6-P2. No differences could be discerned in enzyme activities between the CLL and the normal T and non-T lymphocytes. show less ...
1A5U: Structure of the bis(Mg2+)-ATP-oxalate complex of the rabbit muscle pyruvate kinase at 2.1 A resolution: ATP binding over a barrel.
There were no significant differences in sex, plasma ferritin level, use of pre-transplant chelation therapy, transfusion burden in the 12 months prior to HSCT, adapted EBMT-score, conditioning regimen, relation to donor, graft type, donor-recipient sex combination, or transplant source.. In conclusion, herein we discuss the first global study on the outcome of all patients known to have undergone HSCT in PKD. Since guidelines for HSCT in PKD are lacking, this report may be a helpful first step toward future protocols. Compared to published survival rates for other forms of hereditary anemias, cohorts that are otherwise comparable in age, time period and transplant hospital, the overall survival rate after HSCT in PKD is relatively low.11-13 The present analysis of all 16 PKD patients known to be transplanted to date showed a three-year overall survival of 65%. Significantly better survival was observed for patients transplanted before the age of ten. A negative effect of age on survival is also ...
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Lara had two healthy, big litters of kittens and Bertta one litter of three. They have never been sick in their life. They are both screened negatives for HCM and any other heart conditions, they are big, strong, good mothers, wonderful temperaments, they have multiple titles both in FIFE and TICA. Bertta is full adult whited. They were perfect breeding cats and still are perfect pets. And then came this. About 6 weeks ago I had never heard about PK-def, or didin´t know what it really is. Now I know more than I ever wanted ...
Thats really interesting, thanks for posting. Its especially interesting how it can be mistaken for FIP. I dont know if its just because I come into contact with more Bengal owners over time, but it does seem to me that FIP-like symptoms are being reported more regularly and I have been wondering if they are all FIP or not. Tragically it probably doesnt change the outcome for the poor owner but knowledge is vital for future generations ...
The objective of the present work consisted on determining the effects of PTS and Pyk isozymes inactivation on cell physiology, metabolic flux distribution and PEP availability for aromatics biosynthesis. The inactivation of PTS in E. coli abolishes PEP-dependent glucose transport; therefore PYR production from PEP is dependent only on Pyk isozyme activities. In this study, by inactivating each Pyk isozyme in a PTS- glc+ background, strains were generated where the PEP to PYR reaction was dependent only on PykA or PykF activity. These strains were characterized by flux analysis, thus providing the first quantitative description of the metabolic consequences of the sequential elimination of activities catalyzing the PEP to PYR reaction.. The inactivation of PTS in E. coli causes a strong reduction in qGlc and μ, therefore, such mutant strains display a PTS- glc- phenotype. To improve qGlc and μ, strain VH33 has a chromosomal modification that increases its capacity for non PTS-dependent glucose ...
Pyruvate kinase (PK), an important glycolytic enzyme that catalyzes the final step of glycolysis through an irreversible mechanism to produce energy for the cell, contains nine cysteines, some of which are highly reactive and critical for function. This research sought to develop a protocol to measure quantitatively the functionality of PK under different experimental conditions. Using a three stage, consistent procedure, it was possible to analyze the effects of thiol modification by Ellmans Reagent (DTNB) and oxidation by hypochlorous acid (HOCl) on PK activity. Results showed that both DTNB and HOCl inhibited activity at high concentrations, which illustrates that some cysteines are essential for PK to catalyze its reaction. Furthermore, analysis of cysteine labeling with 5-iodoacetamidofluorescein on SDS-PAGE demonstrates that not all cysteines must be modified to see inhibitory effects. Additionally, incubation studies with ATP and fructose-1,6-bisphosphate, known regulators with different binding
Although Agios is involved in some relatively early stage work on pyruvate kinase deficiency -- a genetic disorder that affects red blood cells ability to carry oxygen -- its the companys oncology platform thats most exciting. Specifically, Agios work with IDH mutant inhibitors is what has me, and Wall Street, excited. Normal IDH enzymes help to generate energy for cells by breaking down nutrients; however, mutant IDH creates a molecule that fails to mature and tends to proliferate rapidly. Thus, Agios approach of inhibiting this mutant form of IDH (IDH1 and IDH2) is believed to have anti-cancer effects.. Agios work is so exciting it got the attention of Celgene (NASDAQ:CELG) years ago, with Celgene eventually licensing the rights to IDH2 mutant inhibitor AG-221, and IDH1 mutant inhibitor AG-120. At the American Society of Hematologys annual meeting in December, Agios announced that AG-221 generated an evaluable response in 37% of patients with relapsed or refractory acute myeloid ...
Blocking interaction of the immune checkpoint receptor PD-1 with its ligand PD-L1 is associated with good clinical outcomes in a broad variety of malignancies. High levels of PD-L1 promote tumour growth by restraining CD8+ T-cell responses against tumors. Limiting PD-L1 expression and function is therefore critical for allowing the development of anti-tumour immune responses and effective tumour clearance. PKM2 is also a key player in regulating cancer as well as immune responses. PKM2 catalyzes the final rate-limiting step of glycolysis. Furthermore PKM2 as a dimer translocates to the nucleus, where it stimulates Hif-1α transactivation domain function and recruitment of p300 to the Hif-1α response elements (HRE) of Hif-1α target genes. Here, we provide the first evidence of a role for PKM2 in regulating the expression of PD-L1 on macrophages, dendritic cells (DCs), T cells and tumour cells. LPS-induced expression of PD-L1 in primary macrophages was inhibited by the PKM2 targeting compound TEPP-46.
Background Accumulating studies show that epithelial-mesenchymal changeover (EMT) plays a part in tumor metastasis. of leptin on breasts cancer tumor cells was examined. Besides a range of pathway inhibitors aswell as RNA disturbance concentrating on pyruvate kinase M2 (PKM2) had been utilized to clarify the root system of leptin-mediated EMT in vitro and in vivo. Outcomes The results showed that leptin marketed breasts cancer tumor cells EMT visibly turned on the PI3K/AKT signaling pathway and upregulated PKM2 appearance. An antibody against the leptin receptor (anti-ObR) as well as the PI3K/AKT signaling pathway inhibitor LY294002 considerably abolished leptin-induced PKM2 appearance and EMT-associated marker appearance. SiRNA targeting PKM2 abolished leptin-induced migration invasion and EMT-associated marker appearance partially. In vivo xenograft tests indicated that RNA disturbance against PKM2 suppressed breasts cancer tumor metastasis and development. Conclusions Our data claim that ...
Background Accumulating studies show that epithelial-mesenchymal changeover (EMT) plays a part in tumor metastasis. of leptin on breasts cancer tumor cells was examined. Besides a range of pathway inhibitors aswell as RNA disturbance concentrating on pyruvate kinase M2 (PKM2) had been utilized to clarify the root system of leptin-mediated EMT in vitro and in vivo. Outcomes The results showed that leptin marketed breasts cancer tumor cells EMT visibly turned on the PI3K/AKT signaling pathway and upregulated PKM2 appearance. An antibody against the leptin receptor (anti-ObR) as well as the PI3K/AKT signaling pathway inhibitor LY294002 considerably abolished leptin-induced PKM2 appearance and EMT-associated marker appearance. SiRNA targeting PKM2 abolished leptin-induced migration invasion and EMT-associated marker appearance partially. In vivo xenograft tests indicated that RNA disturbance against PKM2 suppressed breasts cancer tumor metastasis and development. Conclusions Our data claim that ...
Compounds and uses | Therapeutically active compounds and their methods of use | Crystalline forms of a biphenyl compound | Pyrimidine compounds for the treatment of hepatitis C | Inhibitors of glutaminyl cyclase |
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Deficiencies in the enzyme pyruvate kinase (PK), the key rate-limiting step in the glycolytic metabolic pathway, might protect some humans against infections by Plasmodium falciparum, the main parasite responsible for causing malaria, according to Philippe Gros of McGill University in Montreal, Quebec, Canada, and his collaborators. Mitochondria are absent from red blood cells, a major host target for such parasites. Hence, defects in host glycolysis, while problematic to humans carrying traits affecting this metabolic pathway, also could prove detrimental to P. falciparum parasites within those cells and, thus, could partly protect such individuals against malaria, the Canadian researchers say. Meanwhile, for those individuals who are heterozygous, although the parasites are only partly blocked when invading such cells, protective phagocytosis of parasites is enhanced-making this host situation
In contrast to the case in liver and skeletal muscle, the role of AMPK in β-cell functions is less clear. Glucose stimulation of β-cells has been associated with a reduction in the AMP/ATP ratio and decreased AMPK activity (28). Activation of AMPK by 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) at 200 μmol/l was reported to inhibit glucose-stimulated upregulation of liver-type pyruvate kinase (L-PK) promoter activity and pre-proinsulin promoter activity in MIN6 cells (29). Regarding insulin secretion, diverse effects have been observed with 1 mmol/l AICAR; it acutely (within 5 min) enhances 10 mmol/l glucose-stimulated insulin secretion, but inhibits it in the later phase by ∼50% (28). The effect of AICAR on insulin secretion may also be affected by glucose concentrations. Thus, in the presence of 1 mmol/l AICAR, insulin secretion was inhibited by a high glucose concentration, whereas it was enhanced by a low glucose concentration in rat islets (28). The effects of AICAR ...
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TY - JOUR. T1 - JMJD5 regulates PKM2 nuclear translocation and reprograms HIF-1α-mediated glucose metabolism. AU - Wang, Hung Jung. AU - Hsieh, Ya Ju. AU - Cheng, Wen Chi. AU - Lin, Chun Pu. AU - Lin, Yu Shan. AU - Yang, So Fang. AU - Chen, Chung Ching. AU - Izumiya, Yoshihiro. AU - Yu, Jau Song. AU - Kung, Hsing Jien. AU - Wang, Wen Ching. PY - 2014/1/16. Y1 - 2014/1/16. N2 - JMJD5, a Jumonji C domain-containing dioxygenase, is important for embryonic development and cancer growth. Here, we show that JMJD5 is up-regulated by hypoxia and is crucial for hypoxiainduced cell proliferation. JMJD5 interacts directly with pyruvate kinase muscle isozyme (PKM)2 to modulate metabolic flux in cancer cells. The JMJD5-PKM2 interaction resides at the intersubunit interface region of PKM2, which hinders PKM2 tetramerization and blocks pyruvate kinase activity. This interaction also influences translocation of PKM2 into the nucleus and promotes hypoxiainducible factor (HIF)-1α-mediated transactivation. JMJD5 ...
The major research objective of our laboratory is to understand the biochemical and genetic basis for cell growth regulation by growth factors and hormones. Research from our laboratory has led to the elucidation of a pathway by which growth factors stimulate nutrient uptake and cellular metabolism, leading to increased cell growth and cell survival. Defects in homeostatic control of this signaling network can lead to cancers or to diabetes or metabolic disease. A central node in this network is the enzyme phosphoinositide 3-kinase. In order to explore the in vivo role of this network we are generating mice in which components of the network can be switched on or off to determine their effects on cancers and other diseases References: Manning BD, Cantley LC. AKT/PKB signaling: navigating downstream. Cell. 2007 Jun 29;129(7):1261-74. Christofk HR, Vander Heiden MG, Wu N, Asara JM, Cantley LC. Pyruvate kinase M2 is a phosphotyrosine-binding protein. Nature. 2008 Mar 13;452(7184):181-6. Christofk HR,
1AQF: Ligand-induced domain movement in pyruvate kinase: structure of the enzyme from rabbit muscle with Mg2+, K+, and L-phospholactate at 2.7 A resolution.
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
During pregnancy, many women experience remission of autoimmune diseases like multiple sclerosis and uveitis. Now, scientists have described a biological mechanism responsible for changes in the immune system that helps to explain the remission.. The expression of an enzyme known as pyruvate kinase is reduced in immune cells in pregnant women compared to non-pregnant women, according to Howard R. Petty, Ph.D., biophysicist at the University of Michigan Kellogg Eye Center and Roberto Romero, M.D., of the National Institutes for Health.. The study, which appears online ahead of print in the August issue of the American Journal of Reproductive Immunology, also reports that expression of the enzyme is lower in pregnant women compared to those with pre-eclampsia, a condition with inflammatory components.. The study is significant because the newly discovered mechanism points to a pathway that could be targeted for treatment. "It may be possible to design drugs that mildly suppress pyruvate kinase ...
Learn more about Pyruvate at Blake Medical Center Supplement Forms/Alternate Names Dihydroxyacetone Pyruvate (DHAP) Calcium Pyruvate Magnesium Pyruvate Potassium...
Calcium Pyruvate aids in the reduction of fat and increases stamina. Pyruvate is widely used for weight loss enhancement and exercise endurance, and is naturally found in red apples, cheeses, and red wine. A discovery made at the University of Pittsburgh School of Medicine showed that a diet supplemented with Pyruvate increased fat loss by up to 18% and minimized the associated loss of body protein. Normally, during dietary restriction to promote fat loss, there is always a corresponding loss of muscle, but this study shows pyruvate to be an effective fat burner without the side effects associated with low calorie starvation diet plans. INGREDIENTS: Calcium Pyruwate 750mg DIRECTINS: (Adults Only) One to three capsules per as desired. Not recommended for pregnant or lactating woman.. Features ...
Research in our lab focuses on the structure, function and inhibition of key enzymes involved in infection and disease. We are also interested in the evolution of enzyme function, and conversely its design and manipulation.We study a variety of enzymes: from those responsible for the biosynthesis of amino acids, in particular lysine, since these are validated drug targets; to glycolytic enzymes, such as pyruvate kinase, since these are tractable model systems to understand enzyme allostery. The list is ever increasing.A common theme in the lab is the role protein-protein interactions in a variety of biological systems, mostly derived from bacteria, but more recently including eukaryotic proteins involved in cancer, where we hope to address the twin problems of how and why proteins form complexes and the functional consequences of these associations.. ...
how is question 21 D? I thought you increase glycolysis so increased F-2.6 BP and decrease gluconeogenesis: so decreased Pyruvate kinase and PEP carboxykinase. any help appreciated!
ヤギ・ポリクローナル抗体 ab118499 交差種: Rb 適用: WB,IP,IHC-P,Conjugation,Flow Cyt,Dot…Pyruvate Kinase抗体一覧…画像、プロトコール、文献などWeb上の情報が満載のアブカムの Antibody…
Lentivirus with CMV promoter-driven expression of pyruvate kinase, muscle (PKM2), transcript variant 5 in pLenti vector with puromycin selection and C-terminal Myc and FLAG tags.
Calcium Pyruvate list and information including what is Calcium Pyruvate, health benefits and usage indications. Find articles and product list for other top low-carb products, fat-burners, nutrition bars and shakes.
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How is R-type pyruvate kinase abbreviated? R-PK stands for R-type pyruvate kinase. R-PK is defined as R-type pyruvate kinase rarely.
Thirteen Cases of Erythrocyte Pyruvate Kinase Deficiency Associated with Hereditary Hemolytic Anemia:-Clinical and Biochemical Studies- (1981 ...
Breast cancer is a leading cause of cancer death in women [1]. Accumulating evidence has shown that obesity is a significant risk and negative prognosis factor for breast cancer [2]. Adipose tissue plays a crucial role as an energy storage depot, and currently, there is clear evidence that adipocytes act as endocrine cells and produce various biologically active substances, such as growth factors, cytokines, adipokines and leptin [3, 4]. In spite of the strongly suggested association between obesity and breast cancer, the underlying molecular mechanisms are not known clearly. Previous studies indicate that leptin, one of the adipokines secreted from adipocytes, is an important factor that links obesity with breast cancer [1, 5].. Leptin, a 16-kDa single-chain proteohormone encoded by the LEP gene, is expressed in a variety of tissues, including placenta, ovaries, mammary epithelium, bone marrow, and lymphoid tissues [6-9]. Leptin acts through specific leptin receptors (ObRs) and is a key factor ...
The experiments reported in the present study were designed to determine which glycolytic enzymes are associated with SR from skeletal and cardiac muscle and whether the ATP generated from these glycolytic reactions can support the SR Ca2+-ATPase and 45Ca pumping into the SR. Our results indicate that the entire chain of glycolytic enzymes from aldolase onward, including aldolase, GAPDH, PGK, phosphoglyceromutase, enolase, and pyruvate kinase are bound to SR membranes in cardiac and skeletal muscle as evidenced by the ability of glycolytic substrates and cofactors (without ATP) to support 45Ca transport. IAA, an inhibitor of GAPDH, eliminated SR 45Ca transport supported by FDP (the substrate for aldolase), but transport was completely restored by PEP, indicating that both of the ATP-producing glycolytic enzymes, GAPDH/PGK and pyruvate kinase, were associated with the SR and functionally capable of providing ATP for the Ca2+ pump. Addition of a soluble hexokinase ATP trap eliminated 45Ca ...
View Notes - Fall 08 Exam 2 from MCDB 310 at University of Michigan. e. Phosphopentose isomerase a. Pyruvate carboxylase b. Pyruvate kinase c. PEP carboxykinase d. Glucose 6-phosphatase e. Fructose