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Biosynthesis of amino acids, nucleotides and related molecules,…

- - - - Glu provides most amino groups
      - Gly is precursor for purines
      - Asp is precursor for pyrimidines
      - Nucleotide pools are kept low
        
        limit rates of transcription
        and replication.
    - - Synthesis begins with reaction of 5-phosphoribosyl 1-
        pyrophosphate (PRPP) with Glu.
      - The first intermediate with a full purine ring is inosinate (IMP)
      - Synthesis of AMP and GMP from IMP
      - Regulation of Purine Biosynthesis in E. coli Largely Consists of Feedback Inhibition
      - Catabolism of Purines
        
        Conversion of Uric Acid to Allantoin, Allantoin, and Urea
        
        Degree of further oxidation of uric acid
        is organism dependent.
        
        Excess Uric Acid Seen in Gout
        
        Painful joints (often in toes) due to deposits of sodium
        urate crystals
        
        May involve genetic under-excretion of urate and/or may
        involve overconsumption of fructose
        
        treated with xanthine oxidase inhibitor allopurinol
    - - Unlike purine synthesis, pyrimidine synthesis proceeds by first making the pyrimidine ring (in the form of orotate) and then attaching it to ribose 5-phosphate
      - Feedback Inhibition
        
        ATCase is inhibited by end-product CTP and is
        accelerated by ATP.
      - Cetabolism of Pyrimidines
        
        Leads to NH4+ and urea
        
        Can produce intermediates of CAC
- - - - One type affects activity
      - The other type affects substrate specificity in
        order to maintain balanced pools of nucleotides.
- - - - Are electron transfer processes
      - Use Mo cofactor
      - Involve multiple redox cofactors, such as Fe-S, NADH,
        NADPH, ferrodoxin, flavodoxin, and so on
- - - - Ornithine comes from
        the urea cycle
  - - - : Asp can lead to Lys, Met, Thr, and Ike. Use of isozymes, all regulated by different effectors, allows E. coli to produce the amino acids when needed.
  - - - Porphyrin makes up the heme of hemoglobin, cytochromes, myoglobin
        
        Defects in Heme Biosynthesis
        
        Mutations or misregulaton of enzymes in the heme
        biosynthesis pathway lead to porphyrias.
        
        Accumulation of precursor uroporphyrinogen I
        
        Urine becomes discoloredUrine becomes discolored
        
        Urine becomes discolored
        
        Skin is sensitive to UV light.
        
        There is a craving for heme
      - Glycine or Glutamate Is the Precursor
        to Porphyrins
      - Heme Is the Source of Bile Pigments
        
        Heme from degradation of erythrocytes is degraded
        to bilirubin in two steps:
        
        Heme oxygenase linearizes heme to create
        biliverdin, a green compound (seen in a bruise).
        
        Biliverdin reductase converts biliverdin to bilirubin, yellow compound that travels bound to serum albumin in the bloodstream
        
        Jaundice Is Caused by Bilirubin Accumulation
        
        impaired liver (in liver cancer, hepatitis)
        
        blocked bile secretion (due to gallstones,
        pancreatic cancer)
        
        insufficient glucouronyl bilirubin transferase to
        process bilirubin (occurs in infants)
  - - - Requires glycine, arginine,
        and S-adenosyl-methionine
- - - - Enzymatic Transamination
        
        Catalyzed by aminotransferases
        
        Uses the pyridoxal phosphate (PLP) cofactor
        
        L-Glutamine acts as a temporary storage of nitrogen.
      - Ammonia Collected in Glutamate Is
        Removed by Glutamate Dehydrogenase
        
        Oxidative deamination occurs
        within mitochondrial matrix.
        
        Pathway for ammonia excretion; trans deamination =transamination + oxidative deamination
  - - - This is the second nitrogen-acquiring reaction.
    - - Argininosuccinase cleaves fumarate from argininosuccinate, resulting in arginine.
      - Ornithine is able to serve as a substrate for the next round of the cycle.
- - - - THF
        
        a Versatile Cofactor
        
        transfer 1-carbon
        
        formed from folate
      - adoMet
        
        methyl transfer
        
        synthesized from ATP and methionine.
        
        Regeneration uses N5-methyl THF
      - biotin