BIOC 3560 Carb metabolism.docx

Pfk 2fbpase 2 is a bifuncitonal enzyme where the two

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PFK-2/FBPase-2 is a bifuncitonal enzyme where the two activities are reciprocally regulated: o Phosphorylation by protein kinase A (in response to glucagon) activates FBPase- 2 and inactivate PFK-2 o Dephosphorylation by phosphoprotein phosphatase (in response to insulin) activates PFK-2 and inactivates FBPase-2 o Xylulose 5-phosphate (pentose pathway) also allosterically upregulates phosphoprotein phosphatase Isozyme-specific responses of PFK-2/FBPase-2 to phosphorylation Even while gluconeogenesis occurs in the live, other tissues (eg. cardiac muscle) continue glycolysis This requires that key enzymes are differentially regulated in these tissues These tissues have different PFK-2/FBPase-2 isozymes o Liver isozyme: phosphorylation on Ser 32 activates FBPase-2 o Cardiac muscle isozyme: phosphorylation on Ser 406 and Thr 475 activates PFK- 2 Step 10 of glycolysis/step 1 of gluconeogenesis are reciprocally regulated by acetyl-CoA In the liver only, pyruvate kinase L is in its phosphorylated, inactive form (in response to glucagon activating PKA) PP converts it to its active L/M form through dephosphorylation Pyruvate kinase L/M can be found in all glycolytic issues, including liver where it can convert PEP to pyruvate Pyrvate can then turn to Ala through transamination Ala inhibits pyruvate kinase, as well as ATP, acetyl-CoA and long-chain Fas F1,6BP activates it Pyruvate kinase reglation again, but different Pyruvate kinase is allosterically activated by F1,6BP – the first molecule committed to glycolysis Pyruvate kinase is allosterically inhibited by ATP, acetyl-CoA, long chain Fas and Ala (1 step from pyruvate) These all signal abundant energy
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The liver has a different pyruvate kinase isoform this isoform is phosphorylated by PKA in response to the hormone glucagon (which signals low blood sugar) This slows liver PK, reserving scarce sugar for organs that need it Pyruvate carboxylase Acetyl-CoA (+) ADP (-) PEP carboxykinase ADP (-) TOPIC 2 – PENTOSE PHOSPHATE PATHWAY, GLYCOGEN METABOLISM, REGULATION Pentose phosphate pathway Two phases: o Oxidative oxidation of glucose 6-P produces 2 NADPH and ribulose 5- phosphate (=> ribose-5-phosphate) o Non oxidative: isomerization/rearrangements Glycolytic intermediates Glucose 6-phosphate Xylulose 5-phosphate (modulator of phosphatase that stimulates liver PFK-2) Products of the oxidative phase o For the synthesis of nucleotides (ribose 5-phosphate) o Reductive biosynthesis (NADPH), for eg. FAs Products of non-oxidative phase o Replenish glucose 6-phosphate and glycolytic intermediates o Source of xylulose 5-phosphate Non-oxidative phase Transaldolase/transketolase can transfer 2/3 carbon atoms between sugar phosphates This allows you to rearrange 5C molecules into 6C molecules The final 3C sugars are glyceraldehyde-3P, which can turn into glucose-6P by gluconeogenesis steps NET: 6 x 5C 5 x 6C Regulation of the pentose phosphate pathway Glucose 6-phosphate dehydrogenase o Stimulated by NADP+ o Inhibited by NADPH
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