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Chem 454: Regulatory Mechanisms in BiochemistryUniversity of Wisconsin-Eau Claire
Lecture 13 - Integration of Metabolism
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TextMetabolism is not a collection of isolated pathways.
Introduction
3
TextRecurring motifs of regulation
Interplay of pathways
Three key crossroads
glucose 6–phosphate
pyruvate
acetyl–CoA
Introduction
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TextTissue and organ differencs
Muscle
Liver
Brain
Adipose tissue
Kidneys
Introduction
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TextMetabolism consists of highly interconnected pathways
1. Interconnected Pathways
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TextCatabolism
ATPReducing Power (NADH, NADPH, FADH2)Biosynthetic precursors
1. Interconnected Pathways
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TextCentral 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
1. Interconnected Pathways
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TextAnabolism and catabolism must be precisely regulated:
Allosteric interactionsCovalent modification
1.1 Recurring Motifs in Metabolic Regulation
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TextAnabolism and catabolism must be precisely regulated:
Enzyme levelsCompartmentalizationSpecialization of organs
1.1 Recurring Motifs in Metabolic Regulation
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TextMajor metabolic pathways and control sites
GlycolysisPhosphofructokinase
1.2 Major Control Sites
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TextMajor 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–KetoglutarateCitric acid cycle also has anabolic role
pyruvate carboxylase
1.2 Major Control Sites
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TextMajor metabolic pathways and control sites
Pentose phosphate pathwayoxidative phase
produces NADPH and ribose 5–phosphatenon-oxidative phase
regenerates glycolytic intermediates
1.2 Major Control Sites
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TextMajor metabolic pathways and control sites
GluconeogenisGlycolysis and gluconeogensis are reciprocally regulated
Glycogen synthesis and degradationHormonally controlledPhosphorylation and allosteric control
1.2 Major Control Sites
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TextMajor metabolic pathways and control sites
Fatty acid synthesis and degradationMatrix vs. cytosol
1.2 Major Control Sites
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TextMajor metabolic pathways and control sites
Fatty acid synthesis and degradationMatrix vs. cytosol
1.2 Major Control Sites
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TextKey junctions:
Glucose 6-phosphate
1.3 Key Junctions
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TextKey junctions:
PyruvateAcetyl–CoA
1.3 Key Junctions
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TextEach organ has a unique metabolic profile
BrainHas nearly absolute requirement for glucose
MuscleUses glucose, fatty acids and ketone bodies
LiverProvides fuel to the brain and muscles
2. Organ Differences
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TextEach organ has a unique metabolic profile
2. Organ Differences
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TextEach organ has a unique metabolic profile
Adipose tissue
2. Organ Differences
