Monday 26 September 2011

LSM2101 Part I Lecture 7 Gluconeogenesis


  • Synthesis of glucose from:
    • lactate
    • glycerol
    • glucogenic amino acids, e.g. alanine
    • odd fatty acid chains -> propionyl-CoA
  • Reverse of Glycolysis, but:
    • Hexokinase -> Glucose-6-phosphatase
    • Pyruvate Carboxylase: pyruvate -> oxaloacetate
    • PEPCK: oxaloacetate -> PEP
    • other enzymes are the same
  • Location: 90% liver, 10% kidney
    • Pyr Carboxylase: in mitochondria
    • PEPCK: in mitochondria or cytosol
    • Transfer from mitochondria -> cytosol:
      • Malate Route (generate NADH)
      • Aspartate Route
      • PEP channel
  • Regulations
    • Pyruvate Carboxylase: (+) acetyl-CoA
    • PFK: (+) AMP, F2,6BP (-)citrate,ATP vs. FBPase: (-) AMP, F2,6BP
    • PFK2: (+)AMP, Pi, F6P (-)citrate, ATP vs. FBPase2: (-) F6P (+)G3P 
  • Diseases
    • Deficient in Pyruvate Carboxylase: lactic acidosis, hypoglycemia
    • Deficient in FBP: no gluconeogenesis
  • Anaerobic glycolysis = production of lactate
    • in erythrocytes, tissues of eyes, skeletal muscle (short of ATP)
    • Recycle of lactate: Cori cycle, in liver
  • Adipose Tissue
    • store fatty acids as triacylglyceride
    • broken to: glycerol + FAs, transported to liver
    • Glycerol -> Glucose
    • FA (odd) -> propionyl-CoA -> succinyl-CoA -> glucose
  • Glucose-Alanine Cycle
    • Pyruvate -> Alanine (transamination), in muscles
    • Alanine -> Pyruvate, in liver

Tuesday 13 September 2011

LSM2101 Part II Lecture 2 Ammonia Production and Detoxification

Conversion of AA to Keto Acids
  • Oxidative Deamination
    • L-AA Oxidase + FMN + Catalase
    • L-Glutamate Dehydrogenase + NAD+
  • Transamination
    • Mechanism: 
      • Transfer of amine group from AA to PLP: 1. Transamination 2. Tauromerization 3. Hydrolysis
      • Transfer of amine group from PLP to Keto-Acid: reverse of above
    • General: 
    • Aspartate-Aminotransferase (Glutamate-oxaloacetate transaminase)
    • Alanine-Aminotransferase (Glutamate-pyruvate Transaminase)
    • AST & AST: indication of damaged cells if found in blood serum.
    • Trasndeamination: Transamination + Oxidative Deamination
    • Importance:
      • Funneling to glutamate for conversion to ammonia.
      • Synthesis of non-essential amino acids.
  • Non-Oxidative Deamination
    • Ammonia Lyases
    • Specific Deaminases:
      • Serine dehydratase (L-serine hydrolase)
      • Threonine dehydratase
      • Cysteine desulfhydrase
Excretion of Ammonia
  • AA -> Glu (1 eq NH3) -> Gln (2 eq NH3): happens in everywhere, transported to kidney or liver.
  • Gln (2 eq NH3) -> Glu (1 eq NH3) + NH4+: only happens in kidney and liver.
  • Ion-trapping mechanism: since NH4+ can't cross cell's membrane, ammonium ions in kidney lumen cannot enter kidney cells.

LSM2101 Part II Lecture 3 The Urea Cycle and Disorders

Lecture 3: Urea Cycle / Ornithine Cycle


  • Urea: NH2-CO-NH2 (first N is from Asp, the other one is from ammonia, C is from CO2)
  • Carbamoyl Phosphate synthesis is a rate-limiting step
  •  Regulation:  Carbamoyl Phosphate Synthetase
    • CP I: ammonia dependent, N-acetylglutamate -> activator, mitochondrial
    • CP II: Amide-N of glutamine, independent from  N-ace glu, cytoplasmic
    • N-acetylglutamate: from Glu + Arg using Acetylglutamate Synthase (N-acteyl Transferase)
  • Kreb's Bicycle
  •  Metabolic Disorder - Hyperammonemia (Defects in enzymes)
    • Hyperammonemia Type I: Carbamoyl Phosphate Synthetase I
    • Hyperammonemia Type II: Ornithine Transcarbamoylase
    • Citrullinemia: Argininosuccinate Synthetase
    • Argininosuccinic aciduria/acidemia: Argininosuccinate lyase/Argininosuccinase
    • Argininemia: Arginase
  • Nitrogen Disposal
    • Ureotelic-Urea: Mammals
    • Ammonotelic-Ammonia: Fishes
    • Uricotelic-Ric Acid: Birds

    Sunday 11 September 2011

    LSM2251 Lecture 4-5 Population

    Part I: Populations & Natural Selection (Molles 4th-C8/5th-C4)
    1. What is a population?
    • ecology: group of individuals of the same species inhabiting the same area
    • genetics: group of interbreeding individuals of the same species isolated from other groups
    2. Process of Natural Selection
    • Inheritance: by Mendel
    • Evolution: change in gene frequency within a population over time.
      • Small-scale evolution: changes in gene frequency in a population from one generation to the next.
      • Large-scale evolution: the descent of different species from a common ancestor over many generations.
    • What is Natural Selection? 
      • Key mechanishm of evolution.
      • The process by which heritable traits that are likely to improve an organism’s chances of survival and successfully reproduce become more common in a population over successive generations.
    • VIST
      • Variation    : genetic variation upon which selection works
      • Inheritance : genetic traits inherited
      • Selection    : favourable traits survive and passed on
      • Time          : evolution happens over generations (small-scale), speciation takes much longer (large-scale).
    • Use it or Lose it: traits that are not actively maintained by natural selection rapidly disappear.
      • Relaxed selection: environmental changes eliminates selection pressure that maintain a trait -> degeneration due to the loss of selection against mutations.
      • Selected loss: driven by natural selection
    3. Population genetics and Natural Selection
     a. Variation within populations
    • phenotypic variation among individuals in a population, effects of genes and environments.
    • Potentilla glandulosa
      • In the same species where there are no genetic difference between populations, all plants would grouw well. (Null Hypothesis)
      • In fact, the plants did not grow equally well
      • Changes in genotype -> optimalization
    • Ecotype: 
      • each ecotype performed best under conditions most closely resembling its natural habitat
      • genetically distinctive and is best adapeted to an optimal habitat.
    b. The Hardy-Weinberg equilibrium
    c. Natural Selection
    d. Evolution by natural selection
    e. Random processes

    Part II: Population Distrbution and Abundance (Molles 4th/5th C9)

    Friday 9 September 2011

    LSM2101 Part II Lecture 1 Overview

    So, Part 2 is about Amino Acid Metabolism.
    I skipped the first part since I've rarely attended the lectures. :D But the first part is about carbohydrate metabolism. Maybe I'll post the summary later.


    Okay then...
    Let's go on to the first lecture of second part of LSM2101:  Overview


    1. Why do we need amino acids?
    protein synthesis, energy & gluconeogenic substrates, neurotransmitter, hormones, heme & nucleotide biosynthesis.


    2. Composition of body
    50% dry matter = protein, 1-2% dry matter = free amino acids, no large reservoir of amino acids.


    3. Where does body gets amino acids?
    dietary proteins (exogenous), breakdown of body's proteins (endogenous), biosynthesis.


    4. Dietary Proteins' Fate
    • Intake:
      • minimum daily req = 30 g for 70kg person
    • Digestion:
    • Absorption & Transportation:
    • Inborn Errors: Aminoacidurias
      • Cystinuria: failure to absorp CystineOrnithineArginineLysine -> Cystine Kidney Stones
      • Hartnup's Disease: failure to absorp Trp, Phe, neutral AA -> Cerebellar ataxia (coordination of involuntary movement), Pellagra-like symptoms.
    5. Nitrogen Balance
    • Balance: Intake = Output
    • Positive N Balance: Intake > Output (Growth, Pregnancy, Refeeding)
    • Negative N Balance: Intake < Output (Starvation, Senescence, Metabolic Stress)

    New New New!

    Hi again blog! Haha, I left you alone again for quite some time...
    :)

    To make this not happen anymore, I decided to post a summary after every LSM lectures I attended.
    It's a good practice, isn't it? Since I can allocate my time both for blogging and studying. :D
    And you'll be a very good place to visit at the end of semester for a quick review. :)

    devina