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Integration of Metabolism and Regulatory Mechanisms in Biochemistry

Explore the interconnected pathways and key crossroads in metabolism regulation. Learn about major control sites and recurring motifs of metabolic regulation, focusing on glucose, pyruvate, and acetyl–CoA. Understand tissue-specific metabolic profiles and the interplay of pathways in organs like the brain, muscle, liver, and adipose tissue.

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Integration of Metabolism and Regulatory Mechanisms in Biochemistry

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  1. Lecture 13 - Integration of Metabolism • Chem 454: Regulatory Mechanisms in Biochemistry • University of Wisconsin-Eau Claire

  2. Introduction • Metabolism is not a collection of isolated pathways.

  3. Introduction • Recurring motifs of regulation • Interplay of pathways • Three key crossroads • glucose 6–phosphate • pyruvate • acetyl–CoA

  4. Introduction • Tissue and organ differencs • Muscle • Liver • Brain • Adipose tissue • Kidneys

  5. 1. Interconnected Pathways • Metabolism consists of highly interconnected pathways

  6. 1. Interconnected Pathways • Catabolism • ATP • Reducing Power (NADH, NADPH, FADH2) • Biosynthetic precursors

  7. 1. Interconnected Pathways • Central Themes • ATP is the universal energy currency • ATP generated by oxidation of fuel molecules • NADPH electron donor in reductive biosynthesis • Biosynthetic precursors • Biosynthetic and degradative pathways are distinct

  8. 1.1 Recurring Motifs in Metabolic Regulation • Anabolism and catabolism must be precisely regulated: • Allosteric interactions • Covalent modification

  9. 1.1 Recurring Motifs in Metabolic Regulation • Anabolism and catabolism must be precisely regulated: • Enzyme levels • Compartmentalization • Specialization of organs

  10. 1.2 Major Control Sites • Major metabolic pathways and control sites • Glycolysis • Phosphofructokinase

  11. 1.2 Major Control Sites • Major metabolic pathways and control sites • Citric acid cycle and oxidative phorphorylation • Electron donors are oxidized an recycled back to the citric acid cycle only if ADP is simultaneously phosphoryated to ATP. • ATP inhibits activity of • Isocitrate dehydrogenase • α–Ketoglutarate • Citric acid cycle also has anabolic role • pyruvate carboxylase

  12. 1.2 Major Control Sites • Major metabolic pathways and control sites • Pentose phosphate pathway • oxidative phase • produces NADPH and ribose 5–phosphate • non-oxidative phase • regenerates glycolytic intermediates

  13. 1.2 Major Control Sites • Major metabolic pathways and control sites • Gluconeogenis • Glycolysis and gluconeogensis are reciprocally regulated • Glycogen synthesis and degradation • Hormonally controlled • Phosphorylation and allosteric control

  14. 1.2 Major Control Sites • Major metabolic pathways and control sites • Fatty acid synthesis and degradation • Matrix vs. cytosol

  15. 1.2 Major Control Sites • Major metabolic pathways and control sites • Fatty acid synthesis and degradation • Matrix vs. cytosol

  16. 1.3 Key Junctions • Key junctions: • Glucose 6-phosphate

  17. 1.3 Key Junctions • Key junctions: • Pyruvate • Acetyl–CoA

  18. 2. Organ Differences • Each organ has a unique metabolic profile • Brain • Has nearly absolute requirement for glucose • Muscle • Uses glucose, fatty acids and ketone bodies • Liver • Provides fuel to the brain and muscles

  19. 2. Organ Differences • Each organ has a unique metabolic profile

  20. 2. Organ Differences • Each organ has a unique metabolic profile • Adipose tissue

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