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"Glycogen phosphorylase, liver form (PYGL), also known as human liver glycogen phosphorylase (HLGP), is an enzyme that in humans is encoded by the PYGL gene on chromosome 14. This gene encodes a homodimeric protein that catalyses the cleavage of alpha-1,4-glucosidic bonds to release glucose-1-phosphate from liver glycogen stores. This protein switches from inactive phosphorylase B to active phosphorylase A by phosphorylation of serine residue 14. Activity of this enzyme is further regulated by multiple allosteric effectors and hormonal controls. Humans have three glycogen phosphorylase genes that encode distinct isozymes that are primarily expressed in liver, brain and muscle, respectively. The liver isozyme serves the glycemic demands of the body in general while the brain and muscle isozymes supply just those tissues. In glycogen storage disease type VI, also known as Hers disease, mutations in liver glycogen phosphorylase inhibit the conversion of glycogen to glucose and results in moderate hypoglycemia, mild ketosis, growth retardation and hepatomegaly. Alternative splicing results in multiple transcript variants encoding different isoforms [provided by RefSeq, Feb 2011]. Structure The PYGL gene encodes one of three major glycogen phosphorylase isoforms, which are distinguished by their different structures and subcellular localizations: brain (PYGB), muscle (PYGM), and liver (PYGL). PYGL spans 846 amino acids and shares fairly high homology in amino acid sequence with the other two isozymes, with 73% similarity with PYGM and 74% similarity with PYGB. Nonetheless, PYGB and PYGM demonstrate greater homology to each other, indicating that PYGL evolved by a more distant descent from the common ancestral gene. This protein forms a homodimer, with each monomer composed of N-terminal and C-terminal domains of nearly equal size. The catalytic site forms at the interface between these two domains and interacts with the required cofactor, pyridoxal phosphate, to bind the substrate glycogen. This cofactor is attached by a covalent Schiff base linkage to Lys-680 in the C-terminal domain. At the opposite side of the enzyme, the regulatory face opens up to the cytosol and contains the phosphorylation peptide, which is phosphorylated by phosphorylase kinase and dephosphorylated by the phosphatase PP1, and the AMP site, which is connected to the active site by an adenine loop. Phosphorylation or binding of the allosteric sites induce conformational change that activates the enzyme. Function As a glycogen phosphorylase, PYGL catalyzes the phosphorolysis of an α-1, 4-glycosidic bond in glycogen to yield glucose 1-phosphate. Degradation of glycogen The glucose 1-phosphate product then contributes to glycolysis and other biosynthetic functions for energy metabolism. As the major isozyme in liver, PYGL is responsible for maintaining blood glucose homeostasis by regulating the release of glucose 1-phosphate from liver glycogen stores. One model suggests that Ca2+ oscillations play a role in activating glycogen phosphorylase in glycogen degradation in liver cells. Through its function in the liver, PYGL is also central to meeting the glycemic demands of the entire body. Though other tissues may express all three forms in different proportions, the purpose of expressing multiple glycogen phosphorylases remains unclear. Clinical Significance PYGL has been implicated in glycogen storage disease type VI, also known as Hers disease, and both type 1 and type 2 diabetes. Glycogen storage disease type VI has been attributed to PYGL deficiency as a result of causal mutations in PYGL gene, including two splice-site mutations and two missense mutations. The function of PYGL in regulating liver glucose production also plays a role in diabetes. Since hyperglycemia in type 2 diabetes is the result of excessive glucose production by the liver, developing a drug that targets PYGL may prove effective in controlling blood glucose levels. Glycogen-induced hepatomegaly in type 1 diabetes and glycogen storage disease type VI present similar clinical manifestations such as liver dysfunction, fasting hypoglycemia, and ketosis. Interactions Inhibitors PYGL has been known to interact with allosteric inhibitors, including Bayer W1807 and sugar derivatives that bind the glucose inhibitor site. In addition, glucose and purines stabilize the inactive conformation of PYGL, thus inhibiting binding to its active site. See also *Glycogen phosphorylase *PYGB References Enzymes "
"Fan Jiachen (, born 21 February 1988) is a Chinese competitor in synchronized swimming. She won 2 silver medals at the 2011 World Aquatics Championships. She was also a reserve for the gold-winning Chinese team at the 2010 Asian Games. Personal life Fan Jiachen married footballer Zhu Yifan in 2014. References * Profile Living people Chinese synchronized swimmers 1988 births World Aquatics Championships medalists in synchronised swimming Synchronized swimmers from Beijing Artistic swimmers at the 2010 Asian Games Asian Games medalists in artistic swimming Synchronized swimmers at the 2011 World Aquatics Championships Asian Games gold medalists for China Medalists at the 2010 Asian Games "
"Anthony J. Garcia (1953), known as Tony Garcia, is a playwright and the current Executive Artistic Director of Su Teatro in Denver, Colorado. He has written over 20 original plays and has served as Su Teatro's artistic director since 1989. Biography Early life Garcia grew up in Denver, Colorado and has mentioned that his family lost their home as a result of the construction on Denver's Auraria Campus in the late 1960s. Education Garcia began attending the University of Colorado at Boulder in the fall of 1973 and dropped out in the spring of 1974. He later graduated from the University of Colorado at Denver with a Bachelor of Arts in Theater. Garcia has since completed several fellowships, including the Rockefeller Fellowship in Theater arts in 2006, the United States Artists Fellowship in 2006, and the Livingston Fellowship from the Bonfils Stanton Foundation in 2011. Career Garcia started out as a musician for Su Teatro while still a student in 1972. He later took on roles as an actor until 1989, when he became Su Teatro's Executive Artistic Director. Since writing his first play in 1986, Garcia has written plays consistently, finishing one every three to four years. Garcia spearheaded Su Teatro's fundraising campaign to raise $4.5 million for the theater's move to its new facility in the Denver's Santa Fe Arts District in 2010. Garcia has also served as a faculty member for the National Association of Latino Art and CultureLeadership Institute. He currently still does work as a peer trainer for the Colorado Creative Industries’ Peer Assistance Network, is a member of the Western States Arts Federation’s Board of Trustees, and is an adjunct professor at Metro State College in Denver. Awards * Denver Post Theater Person of the Year (2010) * Artist residency at the Island Institute in Sitka, Alaska (2009) * University of California Irvine Chicano Literary Award (1989) Plays In chronological order of first publication. * La Familia Sin Fabiano (1974) * El Corrido Del Barrio, (1976) * Joaquin's Christmas (1976) * Mrs. Quintana's Living Room (1978) * Ludlow: El Grito De Las Minas (1980) * Intro to Chicano History:101 (1982) * Serafin Cantos y Lagrimas (1984) * The Day Ricardo Falcon Died (1986) * The Miracle at Tepeyac (1989) * Lydia Mendoza: La Gloria De Tejas (1991) * Obsidian Rain (1992) * Little Hands Hold the Wind (1993) * La Carpa Aztlan Presents I Don't Speak English Only (1994) * The Return of the Barrio Moon (1996) * Yerma (adaption, 1998) * Papi, Me and Cesar Chavez (2000) * The Westside Oratorio (2004) * El Sol Que Tu Eres (2005) * When Pigs Fly and Men Have Babies (2006) * To Colorado on a Christmas Night (2008) * The Last Lamented Dance of the Rainbow Ballroom (2010) * Enrique's Journey (2010) * Chicanos Sing the Blues (2011) * Amorcito Corazon (2013) * Mestizo (adapted from the album by Daniel Valdez, 2013) * El Rio: Las Lagrimas de la Llorona (2013) * Cuarenta y Ocho (2014) * La Tierra: El Corazon de mi Madre (2015) References American dramatists and playwrights Living people Hispanic and Latino American dramatists and playwrights American writers of Mexican descent Year of birth missing (living people) "