Neufield.txt

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emm64
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147877
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Neufield.txt
Updated:
2012-04-16 00:56:42
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Neufield Systems S2
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Neufield Systems 2 S2
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  1. ´╗┐Glucose Transporters
    • GLUT2 pancreas liver, high Km, proportional plasma conc
    • GLUT3 brain-Low Km
    • GLUT4 muscle adipose, insulin sensitive
  2. Glucokinase (GK)
    • glucose->G6P F6P
    • liver pancreatic(beta) cells
    • amplified by nucleus translocation
    • glucose sensor-> high Km (other cells have hexokinase with low Km)
  3. Glycolysis Control Points
    • 2 of 8 steps irreversible
    • upregulators-AMP, F2,6-BP
    • inhibitors-ATP, citrate, alanine, G6P, H+
    • 1. PFK-phosphofructokinase
    • G6P->F1,6BP
  4. Glucagon
    • increses cAMP-PKA in liver
    • phosphorylates bifunctional PFK-2 to decrease F26BP
    • phosphorylates Pyruvate Kinase->stop glycolysis
    • INHIBITS GLYcOLYSIS
  5. Pyruvate Dehydrogenase
    • PDH
    • pyruvate->Acetyl CoA
    • inhibited by NADH, acetyl CoA, ATP, glucagon(phosphorylated=inactive)
    • upreg by Ca2+
  6. Citric Acid Regulators
    • Pyruvate dehydrogenase-- inhibited by NADH, ATP, acetyl CoA2)
    • Isocitrate dehydrogenase--inhibited by NADH and ATP3)
    • Alpha-ketoglutarate dehydrogenase-- inhibited by NADH, ATP, succinyl CoA
  7. Gluconeogenesis
    • liver function
    • During fast, substrates for gluconeogenesis provided by peripheral tissues
    • (adipose->glycerol)
    • (RBC->lactate)
    • (muscle->alanine)
    • downregulator ADP
    • Enzymes
    • 1. Pyruvate Carboxylase (pyruvate->oxaloacetate)
    • 2. PEPCK (oxaloacetate-->PEP)
    • 3. F1,6 BPhospatase (+citrate) (-AMP, F26BP)
    • 4. G6Phosphatase->allows export of glucose to other tissues
    • Requires 6 ATP (pyruvate->glucose)
  8. G6Phosphatase
    • allows liver to provide glucose to other tissues
    • lumen of the endoplasmic reticulum
    • Requires 5 proteins
    • G6P transporter-- takes G6P into ER
    • Calcium-binding stabilizing protein (SP)
    • G6 Phosphatase
    • Glucose transporter-- bring glucose back out of the cell
    • Phosphate transporter-- bring phosphate back out of the cell
  9. Van Gierke disease
    • Glycogen storage disease, sever fasting hypoglycemia
    • used to be infusion, now uncooked starch
  10. Glycogen Sythase
    • unphosphorylated=ACTIVE
    • UPREG G6P
  11. Glycogen phosphorylase
    • glycogenolysis
    • activated by phosphorylation +glucagon(liver), +epinephrine (muscle)
    • dephosphorylation catalyzed by protein phosphatase 1, stimulated by insulin [non-phosphorylated = ACTIVE
    • inhibited G6P, ATP, Glucose
    • upreg Calcium, AMP
  12. acetyl CoA carboxylase
    • connects glycolysis to lipogenesis
    • Catalyzes the first and rate-limiting step of fatty acid synthesis
    • The formation of malonyl CoA
    • citrate->enzyme from inactive dimer->active polymer
    • inhibited by existing long chain fatty acyl CoA
    • Glucogon, epinephrine phosphorylate ACC (inactivate)
    • Insulin remove phosphatae to make ACC active
  13. Insulin present in FED STATE
    • INCREASE
    • Glucose uptake
    • Glycolysis (liver)-- liver doesn glycolysis for itself when times are good because it doesn't have to supply for other tissues
    • Glycogen synthesis
    • Fat synthesis
    • ==============
    • DECREASE
    • Gluconeogenesis
    • Glycogen breakdown
    • Lipolysis
    • Ketogenesis
  14. Glucagon and epinephrine present in FASTED STATE
    • INCREASE
    • Gluconeogenesis
    • Glycogen breakdown
    • Lipolysis
    • Ketogenesis
    • ============
    • DECREASE
    • Glycolysis (liver)
    • Glycogen synthesis
    • Fat synthesis
  15. Pentose Phosphate Pathway
    • "pentose shunt" or "hexose monophosphate" shunt
    • G6P dehydrogenase is an important enzyme!
    • Synthesis of pentose sugars for DNA, RNA, ATP, NADH, FAD
    • Generate NADPH from NADP+ for biosynthetic reactions
    • Minor functions
    • Interconversion of 3, 4, 5, 6 and 7 carbon sugars1)
    • Generate glycolytic intermediates2)
    • Rate is controlled by levels of NADP+
  16. G6P patways
    • glycogenolysis
    • pyruvate
    • 6phosphoglucanate->Ribose 5 phospate
  17. NADPH
    • Biosynthesis of Fatty acids, Cholesterol, Neurotransmitters, Nucleotides
    • Detoxificationi
    • Reduction of oxidized GSH in erythrocytes: Keeps hemoglobin iron in a ferrous state, Stabilizes erythrocyte membrane
    • Glutathione is a peptide that keeps redox potential within the cell
  18. Glucose 6-phosphate dehydrogenase
    • First step in pentose phosphate pathway
    • Required for generation of NADPH in erythrocytes
    • Hemolytic anemia
    • Many people in world (200 million) that have G6P dehydrogenase that is ineffective
    • RBCs may get these Heinz bodies that are denatured proteins,
    • May confer selective advantage against malaria parasite

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