Summary of Metabolism

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Summary of Metabolism
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Basic Strategies of Catabolic Metabolism

• Generate ATP
• Generate reducing power
• Generate building blocks for biosynthesis

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ATP

• Universal currency of energy
• High phosphoryl-transfer potential
• ATP hydrolysis drives reactions by changing the
  equilibrium of coupled reactions by a factor of
  108
• Generated from the oxidation of fuel molecules

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Reducing Power

• Oxidation of fuel molecules generates NADH for
  mitochondrial ETC
• NADPH is generated for reducing power for
  biosynthetic processes
• Pentose phosphate pathway is the major source of
  NADPH

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Biomolecules

• Large number of diverse macromolecules are
  synthesized from a small number of building
  blocks.
• Carbon skeletons from generated from the
  oxidation of macromolecules provide the building
  blocks for biosynthetic pathways.
• Central metabolic pathways have anabolic as well
  as catabolic roles.

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Relationships between catabolic and anabolic
processes

• The pathway leading to the biosynthesis of a
  compound are distinct from the pathway leading to
  its breakdown
• This separation ensure that the processes are
  thermodynamically favorable in both directions
• Allows for reciprocal regulation

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Themes in Metabolic Regulation

• Allosteric regulation
• Covalent modification
• Control of enzyme levels
• Compartmentalization
• Metabolic specialization of organs

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Allosteric regulation

• Typically associated with enzymes that catalyze
  irreversible reactions
• Allosteric regulators can cause feed back or
  feedforward regualtion
• Allosteric regulators are often related to the
  energy state of the cell
• This type of regulation allows for immediate
  response to changes in metabolic flux
  (milliseconds to seconds)
• Functions at local level

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Covalent Modification

• Covalent modification of last step in signal
  transduction pathway
• Allows pathway to be rapidly up or down regulated
  by small amounts of triggering signal (HORMONES)
• Last longer than do allosteric regulation
  (seconds to minutes)
• Functions at whole body level

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Enzyme Levels

• Amount of enzyme determines rates of activity
• Regulation occurs at the level of gene expression
• Transcription, translation
• mRNA turnover, protein turnover
• Can also occur in response to hormones
• Longer term type of regulation

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Compartmentalization

• One way to allow reciprocal regulation of
  catabolic and anabolic processes

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Specialization of Organs

• Regulation in higher eukaryotes
• Organs have different metabolic roles i.e. Liver
  gluconeogenesis, Muscle glycolysis
• Metabolic specialization is the result of
  differential gene expression

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Lots ATP G-6-P
Low ATP Need skeltons
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Starvation

• Fuels change from glucose to fatty acids to
  ketone bodies

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