Introduction to metabolism and hexose metabolism

• Catabolic metabolism


  The basic strategy is to form ATP, reducing power, and building blocks for biosynthesis
• Stages of Catabolic Metabolism

  • Breakdown of complex molecules to their component of building blocks.
  • Conversion of building blocks to Acetyl coA (or other simple intermediate).
  • Metabolisn of Acetyl coA to Co2 and formation of ATP
• ATP


  • The universal currency of energy
  • The high phosphoryl transfer potential of ATP enables it to serve as the energy source in muscle contraction, active transport, signal amplification, and biosynthesis
  • The hydrolysis of an ATP molecule changes the equilibrium ratio of products to reactants in a coupled reaction by a factor of about 10^8
  • A thermodynamically unfavorable reaction sequence can be made highly favorable by coupling it to the hydrolysis of a sufficient number of ATP molecules
• ATP generation


  1. Oxidation of fuel molecules such as glucose, fatty acids, and amino acids

  2. The common intermediate is acetyl CoA

  3. The carbon atoms of the acetyl unit are completely oxidized to CO2 by the citric acid cycle with the formation of NADH and FADH2

  4. These electron carriers then transfer their electrons to the respiratory chain

  5. The subsequent flow of electrons to O2 leads to the pumping of protons across the inner mitochondrial membrane which is then used to synthesize ATP

  6. Glycolysis also generates ATP, but the amount formed is much smaller than what is obtained in oxidative phosphorylation
• Substrate level phosphorylation


  Production of ATP or GTP by the transfer of a phosphate group from a substrate directly to ADP or GDP
• Oxidative phosphorylation


  Synthesis of ATP via the transfer of electrons from NADH or FADH2 to O2 by a series of electron carriers
• NADPH


  • The major electron donor in reductive biosynthesis
  • In most biosynthetic processes, the products are more reduced than the precursors, and so reductive power is needed as well as ATP to drive the reactions
  • The required electrons are usually provided by NADPH, most of which is supplied by the pentose phosphate pathway
• Pathways which require reductive power

  • Synthesis of cholesterol and other steroids
  • Fatty acid synthesis and elongation
• Biomolecules


  • Constructed from a small set of building blocks
  • The highly diverse molecules of life are synthesized from a much smaller number of precursors
  • The metabolic pathways that generate ATP and NADPH also provide building blocks for the biosynthesis of more-complex molecules
  • Acetyl CoA, the common intermediate in the breakdown of most fuels, supplies a two-carbon unit for many biosynthetic processes such as those leading to fatty acids, prostaglandins, and cholesterol
  • The central metabolic pathways have anabolic as well as catabolic roles
• Biosynthetic and degradative pathways are almost always distinct
• This separation of biosynthetic and degradative pathways contributes greatly to the effectiveness of metabolic control
• Galactose conversion to glucose 6-phosphate

  1. Phosphorylation of galactose to galactose 1-phosphate by galactokinase

  2. Galactose 1-phosphate acquires uridyl group from UDP-glucose, forming UDP-galactose and glucose 1-phosphate

  3. Galactose moiety of UDP-galactose epimerized to glucose by UDP-galactose 4-epimerase

  4. Glucose 1-phosphate isomerized to glucose 6-phosphate by phosphoglucomutase
• Galactokinase


  Enzyme that phosphorylates galactose to galactose 1-phosphate
• Galactose 1-phosphate uridyl transferase


  Enzyme that catalyzes the reaction forming UDP-galactose and glucose 1-phosphate
• UDP-galactose 4-epimerase


  Enzyme that epimerizes the galactose moiety of UDP-galactose to glucose
• Phosphoglucomutase


  Enzyme that isomerizes glucose 1-phosphate to glucose 6-phosphate
• UDP-glucose is not consumed in the conversion of galactose into glucose, because it is regenerated from UDPgalactose by the epimerase
• Lactose intolerance/hypolactasia


  Condition where adults are unable to metabolize the milk sugar lactose, caused by a deficiency of the enzyme lactase
• Fructose metabolism via fructose 1-phosphate pathway

  1. Phosphorylation of fructose to fructose 1-phosphate by fructokinase

  2. Fructose 1-phosphate split into glyceraldehyde and dihydroxyacetone phosphate by fructose 1-phosphate aldolase

  3. Glyceraldehyde phosphorylated to glyceraldehyde 3-phosphate by triose kinase

  4. Fructose can also be phosphorylated to fructose 6-phosphate by hexokinase, but hexokinase has 20 times greater affinity for glucose
• Fructokinase


  Enzyme that phosphorylates fructose to fructose 1-phosphate
• Fructose 1-phosphate aldolase


  Enzyme that catalyzes the aldol cleavage of fructose 1-phosphate
• Triose kinase


  Enzyme that phosphorylates glyceraldehyde to glyceraldehyde 3-phosphate
• Hexokinase


  Enzyme that phosphorylates fructose to fructose 6-phosphate, but has 20 times greater affinity for glucose
• Glycolysis


  • Degrades glucose to generate ATP
  • Provides building blocks for synthesis of cellular components
• The rate at which glucose is converted to pyruvate in glycolysis is regulated to meet the needs of ATP generation and cellular component synthesis