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Glycogen Metabolism, Glycogenolysis -removes one sugar at a time -(glycogen) phosphorylase -PHOSPHOROLYSIS, not hydrolysis -phosphorylase uses HPO4(2-) -cleaves alpha-1,4 glycosidic bonds ->glucose-1-P product -phos'ase cleaves until 4 from jcn ???? Phosphorylase a(phos'ated), b(not) -by phos'ase kinase(epi->cAMP->PKA) -fully active w/ PKA and Ca++ (on CaM) 'a' or 'b' can be 'R'or 'T' but when 'a', equilibrium shift to R -same mech in liver, mm. -mm. 'b'-(-) by G6P, ATP (can't phos'ate) (+) by AMP, hormones -activates 'b' into R state -liver 'a'-(-) by high glucose (stay in T), Glycogen Metabolism Synthesis Start w/ Glycogenin -protein that glycosylates self -forms initial glycogen primer -remains attached, Storage Diseases-liver ->inability to mobilize glycogen Excess storage in liver -Von Gierke-no G-6-phosphatase -more severe-GNG also impaired -Hier-def. of phosphorylase(liver) -both-fasting hypoglycemia, big liver -can't maintain blood [glucose] ???? Storage Diseases-mm. McArdle-def. phosphorylase (mm.) -can't make G6P->can't make ATP -high [ADP] after moderate exercise -severe pain -fatty acids make ATP after rest -liver okay, no fasting hypoglycemia, Glucose-1-P->Glucose-6-P -using phosphoglucomutase -move P from one OH to another -P from enzyme to sugar to enz -reversible-dep on []s ???? G6P->bypass 1st glycolysis step -get 3 ATP, not 2 per sugar -because of phosphorolysis, Glycogen- -highly branched polymer-more than starch -all non-reducing outside ends -alpha-1,4 linked glucose along chains -alpha-1,6 at branch points -provides ə% total caloric food stores -liver w/ highest [glycogen]~10% by wt -for blood glucose -largest portion by wt in mm. -for muscle work ???? Branching allows: -more ends=more rapid glycogenolysis -less osmotic effect than many chains -excess NL glycogen okay, excess unbranched glycogen=cirrhosis -cytotoxic, Glycogen Synthase -add glucose units via a-1,4 links -UDP-glucose as source (G1P+UTP->UDP-glucose) (by UDP-pyrophosphorylase) -G1P after 1st step of glycolysis -then phosphoglucomutase from glucose, need 1ATP, 1UTP -2 high-energy bonds Re Glycogen Synthase Regulation -inactivated by PKA (epi->cAMP) -or other kinases phos'ate Ser -increase inactivation -activated by insulin-dephos'ate -allosteric-high G6P permit some activity even if phos'ated (b) -aka glyc. synthase 'D' -dep. on G6P, Glucose-1-P->Glucose-6-P -using phosphoglucomutase -move P from one OH to another -P from enzyme to sugar to enz -reversible-dep on []s ???? Glucose-6-P->Glucose+Pi -using glucose-6-phosphatase -ONLY PRESENT IN LIVER -G6P into ER lumen(T1)->hydrolyzed -Pi back out (T2) to cytosol -glucose back out to cell or out (T3) -increase blood [glucose] -all stabilized by SP-Ca++ binding protein, Glycogen Metabolism Glycogenolysis Storage Diseases-liver ->inability to mobilize glycogen Excess storage in liver -Von Gierke-no G-6-phosphatase -more severe-GNG also impaired -Hier-def. of phosphorylase(liver) -both-fasting hypoglycemia, big liver -can't maintain blood [glucose], Glycogenolysis -removes one sugar at a time -(glycogen) phosphorylase -PHOSPHOROLYSIS, not hydrolysis -phosphorylase uses HPO4(2-) -cleaves alpha-1,4 glycosidic bonds ->glucose-1-P product -phos'ase cleaves until 4 from jcn Debranching Enzyme Debranching enzyme-2 parts 1.Transferase-3 glycosyl residues ->to core of glycogen 2.a-1,6-glycosidase -release 4th residue as free glucose -increase blood [glucose], Start w/ Glycogenin -protein that glycosylates self -forms initial glycogen primer -remains attached Propagation Glycogen Synthase -add glucose units via a-1,4 links -UDP-glucose as source (G1P+UTP->UDP-glucose) (by UDP-pyrophosphorylase) -G1P after 1st step of glycolysis -then phosphoglucomutase from glucose, need 1ATP, 1UTP -2 high-energy bonds