Oct 22 - Biochem 423 Robert A Orlando Ph.D FASTING –...

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Unformatted text preview: Biochem 423 Robert A. Orlando, Ph.D. FASTING – GLUCONEOGENESIS WHY DO WE NEED GLUCONEOGENESIS IN THE LIVER? DAILY GLUCOSE NEEDS WHOLE BODY BRAIN GLUCOSE AVAILABILITY BODY FLUIDS TOTAL GLYCOGEN STORES 160 G 120 G 20 G 190 G ONLY ABOUT A 24 HOUR SUPPLY ! 121 | P a g e Biochem 423 Robert A. Orlando, Ph.D. BYPASS REACTIONS OF GLUCONEOGENESIS ‐‐SUMMARY GLUCONEOGENIC ENZYMES ALL INDUCIBLE AND PATHWAY IS REGULATED BY FLOW OF SUBSTRATES INTO THE LIVER. 122 | P a g e Biochem 423 Robert A. Orlando, Ph.D. 1ST LEVEL OF REGULATION ‐‐ GLUCOKINASE LOW GLUCOSE LEVELS IN BLOOD SLOW TRANSPORT OF GLUCOSE INTO THE LIVER 123 | P a g e Biochem 423 Robert A. Orlando, Ph.D. 2ND LEVEL OF REGULATION ‐‐ PHOSPHOFRUCTOKINASE‐1 REMEMBER….INTRAPATHWAY REGULATION BY ATP & AMP LEVELS 124 | P a g e Biochem 423 Robert A. Orlando, Ph.D. REGULATION OF PFK‐1 – BY FRUCTOSE‐2,6‐BISPHOSPHATE WHAT CONTROLS FRUCTOSE‐2,6‐BISPHOSPHATE LEVELS? 125 | P a g e Biochem 423 Robert A. Orlando, Ph.D. 3RD LEVEL OF REGULATION ‐‐ PYRUVATE KINASE transport to mitochondrial matrix 126 | P a g e Biochem 423 Robert A. Orlando, Ph.D. 4TH LEVEL OF REGULATION ‐‐ PYRUVATE CARBOXYLASE ACTIVATION PYRUVATE CARBOXYLASE = STIMULATED BY ACETYL‐COA PYRUVATE DEHYDROGENASE = INHIBITED BY ACETYL‐COA MALATE DELIVERS CARBON FROM TCA CYCLE FOR GLUCONEOGENESIS malate‐aspartate shuttle back to cytoplasm 127 | P a g e Biochem 423 Robert A. Orlando, Ph.D. IN THE CYTOPLASM…. AND RETURN TO THE GLYCOLYTIC PATHWAY…. 128 | P a g e Biochem 423 Robert A. Orlando, Ph.D. 3 MAJOR GLUCONEOGENIC PRECURSORS 129 | P a g e ...
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