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Eric Niederhoffer SIU-SOM

Regulation of Phosphofructokinase-1: Too Much of a Good Theme?. Eric Niederhoffer SIU-SOM. Problem-based learning using electronic patient cases Organ-system, integrated disciplines Specific example - diabetes mellitus/alcoholic ketoacidosis Learning Issues

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Eric Niederhoffer SIU-SOM

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  1. Regulation of Phosphofructokinase-1: Too Much of a Good Theme? Eric Niederhoffer SIU-SOM

  2. Problem-based learning using electronic patient cases Organ-system, integrated disciplines Specific example - diabetes mellitus/alcoholic ketoacidosis Learning Issues Which steps in metabolic pathways are regulated by insulin, glucagon, or other important hormones or metabolites? How do insulin and glucagon balance the degradation, synthesis, and storage of glucose? How does the regulation of glycolysis compare between liver, cardiac muscle and skeletal muscle? Curriculum Context

  3. Liver Glc Liver G6P Heart Liver F6P Heart F16BP PEP Liver Pyr Adipose Acetyl-CoA Glycolysis: Regulatory Steps Glucagon Insulin GK Ep HK F26BPase PFK-2 PFK-1 PK PDH

  4. Glc G6P ATP Citrate PEP H+ F6P PFK-2 PFK-1 F26BP NH4+ AMP Pi F16BP Regulation Focus

  5. Two genes - PFKL (21q), PFKM (12q) Tetramer - muscle (M4), liver/kidney (L4), platelet (M4, M3L, M2L2, ML3, L4) T and R states Activators - AMP, ADP, cAMP, Pi, F6P, F16BP, F26BP, NH4+ Inhibitors - ATP, citrate, PEP, H+ Interaction with renal H+ ATPase Glycogen storage disease VII (Tauri) - autosomal recessive, gout, increased O2 affinity (decreased 23BPG) PFK-1 - Facts

  6. Four genes - PFKFB1 (X), PFKFB2 (1), PFKFB3 (10), PFKFB4 (3) PFK-2 dimer Bifunctional protein (PFK/F26BPase) Activators/inhibitors - similar to PFK-1 except no ATP inhibition Brain no (or low) mRNA detected Skeletal muscle - F6P regulates Phosphorylation - liver (Ser32, N term), cardiac (Ser406[466,483],Thr475, F26BPase) PFK-2 - Facts

  7. Glucagon Ep Insulin F26BPase-PFK-2P Liver PKA PrPase2A F26BPase-PFK-2 F26BPase-PFK-2 Skeletal Muscle F6P↑ F6P↓ F26BPase-PFK-2 Ep Insulin F26BPase-PFK-2 PKA Heart ??? AMPK/AKT/WISK F26BPaseP-PFK-2 F26BPase-PFK-2 Regulation Comparison

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