02.12 - Lee - Pentose Phosphate Pathway

02.12 - Lee - Pentose Phosphate Pathway - Source of the...

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GLUCOSE Fructose 6-P Fructose 1,6-P Triose-P PEP Glucose 6-P Ga3-P DHAP GLYCEROL from triglycerides LACTATE Muscle contraction OXALOACETATE Catabolism of amino acids PYRUVATE Krebs cycle intermediates Source of the precursors for gluconeogenesis. 1 Source of lactate - glycolysis Cori Cycle •Muscle produces lactate during strenuous exercise when oxygen is limiting. •The lactate is transported into the blood and is taken up by the liver, to be resynthesized to glucose. 2 •The catabolism of some of the amino acids leads to intermediates that can be converted either into pyruvate or oxaloacetate/malate (via Krebs cycle), i.e. they are gluconeogenic. •Alanine, derived from muscle, is an important precursor because it also shuttles amino groups from muscle to liver (which is responsible for the disposal of nitrogen as urea). COO - C=O CH 3 COO - C=O CH 2 COO - COO - C-NH 2 CH 3 Pyruvate Alanine COO - C-NH 2 CH 2 COO - Oxaloacetate Aspartate Catabolism of some amino acids provides intermediates that can serve as precursors for gluconeogenesis. 3
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PYRUVATE LIVER MUSCLE Alanine is released into the bloodstream from muscle and is used for gluconeogenesis in the liver. It is derived from amination of pyruvate by transaminase. Glutamate and alanine are the main amino acids transported in the blood. ALANINE transaminase PYRUVATE GLUCOSE ALANINE GLUCOSE Amino-acid α -keto-acid Protein catabolism NH 3 Urea Cycle 2007 Alanine-Glucose Cycle 4 Glycerol, derived from lipids, is a significant source of glucose carbons. Dihydroxyaceto ne phosphate Triglycerides 5 Pentose Phosphate Pathway •Metabolism of –fructose (from sucrose) –galactose (from lactose) 2008 6
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The Pentose Phosphate Pathway •A way of oxidizing glucose 6-phosphate to generate NADPH which is used in biosynthetic reactions as a reducing agent. •An important source of ribose 5’ phosphate for nucleotide biosynthesis. •Also important in plants (photosynthesis). •Features: –A versatile pathway for taking 5 carbon sugars and reversibly rearranging them to generate 6 carbon and 3 carbon intermediates of glycolysis (F6-P and glyceraldehyde 3-phosphate). 7 8 There are two phases: Oxidative phase - 2 step oxidation of G6-P to ribulose 5-P to generate 2NADPH. Nonoxidative phase. Involves interconversion of sugar phosphates. Focus on the metabolically important sugars ribose 5-P fructose 6-P glyceraldehyde 3-P. Remember that all the sugar phosphate reactions are REVERSIBLE. Ribulose 5P is converted to Ribose 5P or xylulose 5P, What do you have? 3 x 5 carbon sugar P’s (1 Ribose 5-P, 2 xylulose 5-P) 2 x F6-P + 1 x GAP 2 C5 <--> C3 + C7 C3 + C7 <--> C6 + C4 C4 + C5 <--> C6 + C3 Net: Three C5’s to two C6’s and one C3 Overview 9
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The C1 aldehyde of G6-P is oxidized while G6-P is in the ring form to yield the lactone (internal ester of C1 carboxylic acid with C-4 hydroxyl group) to generate NAHPH. Glucose 6-phosphate Dehydrogenase
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02.12 - Lee - Pentose Phosphate Pathway - Source of the...

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