biochem unit 4

• Biosynthesis (anabolic) pathways


  Require an input of energy to synthesize complex molecules from simpler ones
• Anabolic pathways in animals

  Use ATP and NADH/NADPH to produce large biomolecules
• Major hormones that regulate metabolic pathways


  • Glucagon (fasting state)
  • Insulin (fed state)
• Glucagon


  Released from the pancreas when blood glucose is low, binds receptors on liver and fat cells
• Insulin


  Released from pancreas when blood glucose is high, binds receptors on fat, liver, and muscle cells
• Signal transduction and hormonal signaling between cells


  1. Signal → reception → transduction → response

  2. Hormones bind receptors initiating signaling cascades resulting in metabolic changes in cell

  3. Hormone does NOT enter the cell
• Pathways turned on during fasting (unfed) state


  • Glycogenolysis (glycogen breakdown) - liver
  • Gluconeogenesis - liver
  • Lipolysis (fat mobilization) - liver/adipose
  • Ketogenesis - liver
• Pathways turned on during fed state


  • Glycogenesis (glycogen synthesis) - liver/muscle
  • Glycolysis - multiple tissues
  • Fatty acid synthesis - liver/adipose
  • Cholesterol synthesis - liver
  • Pentose phosphate pathway - liver and other tissues
• Monosaccharides


  Simple sugars, consist of a polyhydroxy aldehyde or ketone unit
• Disaccharides


  Two monosaccharide units joined together by glycosidic bond
• Oligosaccharides


  Short chains of monosaccharide units, or residues, joined by glycosidic bonds
• Polysaccharides


  Sugar polymers with 10+ monosaccharide units
• Alpha anomers


  Hydroxyl at C-1 is below the plane of the ring
• Beta anomers


  Hydroxyl at C-1 is above the plane of the ring
• Glycosidic bonds


  Covalent linkage joining two monosaccharides
• 1. glycosidic bond


  Formed when a hydroxyl group of one sugar molecule reacts with the anomeric carbon of the other
• 1. glycosidic bond


  Formed between the anomeric carbon atom and an amine
• Glycogen


  • Most glucose units are linked by an α-1,4 glycosidic bonds, with branches formed by α-1,6-glycosidic bonds every 10-12 glucose units
  • The α linkages form compact hollow cylinders
• Reducing sugars


  Sugars that react with oxidizing agents
• Non-reducing sugars


  Sugars that do not react with oxidizing agents
• Glucagon


  Hormone released during fasting state when blood glucose is low
• Pathways activated during fasting (unfed) state


  • Glycogen breakdown → release glucose (liver)
  • Gluconeogenesis → produce glucose (liver)
  • Ketogenesis → produce ketones (liver)
  • Lipolysis → fatty acid release + glycerol release (adipose tissue)
• Glycogen


  • Branched polymer of glucose, with tiers of glucose residues in α1→4 linkage and α1→6 linked branches
• Glycogen breakdown


  Glycogen breakdown releases glucose 1-phosphate, rearranging the remaining glycogen, conversion of G1P to G6P
• Signaling cascade from glucagon/epinephrine to activation of glycogen phosphorylase


  Hormone binds receptor → Activation of G protein → Activation of adenylate cyclase → Increase in cAMP → PKA activation → Phosphorylation of target proteins → Activation of glycogen phosphorylase
• Glycogen phosphorylase


  Catalyzes the cleavage of the α-1,4 glycosidic bonds in glycogen, adding phosphate to form glucose 1-phosphate
• Regulation of glycogen phosphorylase


  Regulated by phosphorylation, binding of allosteric effectors, and by catalytic mechanism
• Gluconeogenesis


  Pathway that converts pyruvate and related 3- and 4-carbon compounds to glucose, mainly occurs in the liver
• Glycolysis cannot simply run in reverse to synthesize glucose due to being exergonic under cellular conditions and requiring large amounts of energy
• Reactions in gluconeogenesis that bypass irreversible steps of glycolysis


  Bypass 1a - pyruvate to oxaloacetate

  Bypass 1b - oxaloacetate to PEP

  Bypass reactions 2 and 3 - glycolysis and gluconeogenesis
• Fructose-2,6-bisphosphate (F 2,6 BP)


  Allosteric effector that stimulates glycolysis and inhibits gluconeogenesis, main determinant of which pathway is active in the liver
• Ketone bodies


  Crucial fuel source during starvation, produced in the liver mitochondria, used as energy source by extrahepatic tissues like the brain
• Fructose 2,6-bisphosphate


  An allosteric effector that helps regulate glucose metabolism
• Fructose 2,6-bisphosphate


  • Stimulates glycolysis
  • Inhibits gluconeogenesis
• Fructose 2,6-bisphosphate is the main determinant of which pathway is active in the liver
• Ketone body formation


  1. Ketone bodies form during starvation

  2. Liver mitochondria are the source of ketone bodies

  3. During fasting, liver uses fatty acids as fuel molecules to generate ATP

  4. Build up of acetyl-CoA allows conversion of acetyl-CoA to ketone bodies
• Ketone bodies


  A crucial fuel source during starvation
• Glucose metabolism during starvation


  1. Protein degradation is initially the source of carbons for gluconeogenesis in the liver

  2. The glucose is then released into the blood
• Ketone bodies


  Water-soluble ketones, acetoacetate and beta-hydroxybutyrate, that supplement glucose as an energy source as they enter the brain where they are oxidized for energy
• Acetone, a minor ketone body, is not metabolized but is eliminated in the breath