Bioche new

• Lipidgebundene Proteine


  ziel: lokal Konz prot ermöglichen unter bioche prozesse

  Prenylierung: c term tetrapeptid mit farnesyl oder geranyl geranyl rest, entsteht thioetherbdg sehr stabil und irrev

  FS acylierung:

  • Myristoylisierung: macht myristoyl prot, stabil (Amid), selten co-translational
  • palmitoylisierung: palmitoyl prot, thioesterbdg, rev, häufig, post-translational
  • GPI linker: c term prot, nur aussenseite membran
• Periphere membranprot


  Monotropisch= nur auf einen seite

  an membran selbst oder integrale prot

  int:

  • ionische bdg & H Brücke
  • Lockere verankerung über amphipatische helix
  • hydrophobe patches

  schon milden Bedingungen= dissoziation von membran

  amphipatische alpha helix —> helical wheel zeichnung
• Import FS


  FS translokase CD36: folgt grad, multifunktional

  FS transportprotein: benutzt ATP, auch gegen grad, mit acyl coA synthethase assoziert
• PLP 


  Transaminase

  decarboxylase

  DH

  Racemase
• Glycogen Synthase Regulation


  Insulin activates PP1 & inhibits GSK3 → active glycogen synthesis, while glucagon & epinephrine inhibit PP1 & activate GSK3 → inactive glycogen synthesis
• Glycogen Synthase Priming Site

  PKA-mediated phosphorylation of the priming site creates a binding site for UDP-glucose, activating glycogen synthase and regulating its activity
• Glycogen synthesis


  1. Glucose converted to glucose 6-phosphate by hexokinase

  2. Glucose 6-phosphate converted to glucose 1-phosphate by phosphoglucomutase

  3. Glucose 1-phosphate becomes UDP-glucose

  4. Glycogen synthase elongates glycogen chain
• Glycogen degradation


  1. Glycogen phosphorylase breaks alpha 1-4 linkages forming glucose 1-phosphate

  2. Phosphoglucomutase converts glucose 1-phosphate to glucose 6-phosphate

  3. Glucose 6-phosphate converted to glucose by glucose 6-phosphatase
• Glycogen phosphorylase


  Exists in active (phosphorylase a) and less active (phosphorylase b) forms
• Activation of glycogen phosphorylase

  1. Phosphorylase b kinase phosphorylates phosphorylase b to convert it to active phosphorylase a

  2. Requires 2 ATP
• Glycogen phosphorylase activation


  • Activated by epinephrine and glucagon
  • Triggered by increased cyclic AMP levels
• Cyclic AMP


  Intracellular second messenger produced from ATP
• Increased cyclic AMP


  Activates protein kinase A
• Protein kinase A


  Activates phosphorylase b kinase
• Phosphorylase b kinase


  Converts phosphorylase b to active phosphorylase a
• Increased ATP levels


  Inhibit glycogen phosphorylase by blocking allosteric site for AMP
• Deactivation of glycogen phosphorylase


  Phosphor protein phosphatase removes phosphate group, converting phosphorylase a to phosphorylase b
• Glycogen synthase


  Exists in active (dephosphorylated) and inactive (phosphorylated) forms
• Activation of glycogen synthase

  Phosphor protein phosphatase 1 (PP1) dephosphorylates and activates glycogen synthase a
• Insulin, glucose, glucose 6-phosphate


  Activate PP1 to activate glycogen synthase
• Glucagon, epinephrine


  Inactivate glycogen synthase by activating glycogen synthase kinase 3
• Regulation of carbohydrate metabolism in liver

  High blood glucose: Insulin triggers glucose uptake, glycolysis, and glycogen synthesis

  Low blood glucose: Glucagon triggers glycogen breakdown and inhibits glycolysis
• Glycogen synthase and glycogen phosphorylase are allosterically and hormonally regulated
• Glycogen phosphorylase vs synthase

  Phosphorylase: aktiviert durch adrenaline, AMP und Ca2+, aktiv wenn 2x phosphoryliert

  synthase: inaktive wenn 3x phosphoryliert, dephos. Durch PP1 und phos durch GSK3
• Protein abbau 


  1 ubiquiniert

  2 proteasome

  3 peptidase
• Ring finger domain (RFD) recognizes specific amino acid sequences or posttranslational modifications on target proteins
• Amino acid


  Contains an amino group, carboxylic acid, and a unique side chain
• Amino acid catabolism


  1. Removing the amino group

  2. Separating the carbon skeletons
• Transamination


  Process of transferring the amino group from an amino acid to an alpha-keto acid
• Ammonia


  Very toxic and causes severe damage and complications
• Transamination reaction


  1. Amino acid transfers amino group to alpha-ketoglutarate

  2. Forming pyruvate and glutamate
• Glutamate has the amino group

  • Glutamate moves to mitochondrial matrix
  • Glutamate dehydrogenase removes amino group via oxidative deamination
• Fates of carbon skeletons from amino acid degradation

  • Gluconeogenesis
  • Ketogenesis
  • Entering citric acid cycle
• Low ATP levels


  Pyruvate converted to acetyl-CoA and enters citric acid cycle
• High ATP levels


  Pyruvate converted to oxaloacetate and diverted to gluconeogenesis
• Amino acids that can enter citric acid cycle

  • Via alpha-ketoglutarate
  • Via succinyl-CoA
  • Via fumarate
  • Via oxaloacetate
• Ketogenic amino acids


  Can be converted into ketone bodies
• Glucogenic amino acids


  Can be converted into glucose
• Proteins are one of three organic fuels, along with glucose from carbohydrates and fatty acids from fats
• Amino acids cannot be stored, so we need to supply them from the diet for protein synthesis