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  <head>
    <title>090-02 One-carbon metabolism, haem synthesis, bilirubin, and specialised amino-acid products</title>
    <ownerName>Integrated Medical Foundations</ownerName>
  </head>
  <body>
    <outline text="One-carbon metabolism, haem, bilirubin, and amino-acid products">
      <outline text="Folate one-carbon cycle">
        <outline text="Tetrahydrofolate carries one-carbon units"/>
        <outline text="Serine hydroxymethyltransferase forms glycine"/>
        <outline text="Methylene form supports thymidylate synthesis"/>
        <outline text="Reduced to methyl tetrahydrofolate"/>
        <outline text="Methionine synthase needs vitamin B12">
          <outline text="B12 deficiency traps folate as methyl form"/>
          <outline text="Nucleotide synthesis fails despite total folate"/>
        </outline>
      </outline>
      <outline text="Methylation and transsulfuration">
        <outline text="S-adenosylmethionine is the main methyl donor"/>
        <outline text="Methylates DNA, RNA, proteins, phospholipids"/>
        <outline text="Plasma homocysteine cannot show methylation potential"/>
        <outline text="Cystathionine beta-synthase starts transsulfuration">
          <outline text="Cysteine for glutathione, taurine, sulfate"/>
          <outline text="Severe deficiency: homocystinuria">
            <outline text="Thrombosis, lens dislocation, skeletal change"/>
          </outline>
        </outline>
        <outline text="Mild hyperhomocysteinaemia from vitamins, kidney">
          <outline text="Vitamin lowering has not uniformly cut events"/>
        </outline>
      </outline>
      <outline text="Folate and B12 deficiency">
        <outline text="Folate lack impairs thymidylate and purines">
          <outline text="Megaloblastic haematopoiesis"/>
          <outline text="Gut and fetal tissues affected"/>
        </outline>
        <outline text="B12 lack also impairs methylmalonyl-CoA mutase">
          <outline text="Methylmalonate rises, nerves injured"/>
        </outline>
        <outline text="Folate alone may let neuropathy progress"/>
      </outline>
      <outline text="Haem synthesis">
        <outline text="Ferrous iron in protoporphyrin ring"/>
        <outline text="Begins and ends in mitochondria"/>
        <outline text="Aminolevulinate synthase: glycine, succinyl-CoA">
          <outline text="Hepatic form repressed by haem, induced by drugs"/>
          <outline text="Erythroid form follows iron and globin"/>
          <outline text="B6 deficiency: sideroblastic anaemia"/>
        </outline>
        <outline text="Zinc-dependent dehydratase forms porphobilinogen"/>
        <outline text="Uroporphyrinogen, then coproporphyrinogen"/>
        <outline text="Ferrochelatase inserts ferrous iron"/>
      </outline>
      <outline text="Lead and porphyrias">
        <outline text="Lead inhibits dehydratase and ferrochelatase">
          <outline text="Anaemia with basophilic stippling"/>
          <outline text="Blood lead and exposure history central"/>
        </outline>
        <outline text="Early precursors: acute neurovisceral attacks">
          <outline text="Abdominal pain, neuropathy, hyponatraemia"/>
          <outline text="Drugs, fasting, alcohol induce haem demand"/>
        </outline>
        <outline text="Later porphyrins: light-dependent skin injury">
          <outline text="Urine, plasma, stool, red-cell patterns"/>
          <outline text="Protect samples from light"/>
        </outline>
        <outline text="Suppress precursors, remove iron, avoid triggers"/>
      </outline>
      <outline text="Bilirubin">
        <outline text="Haem oxygenase opens ring to biliverdin"/>
        <outline text="Unconjugated bilirubin bound to albumin"/>
        <outline text="UDP-glucuronosyltransferase conjugates in liver"/>
        <outline text="Gut microbes form urobilinogen products">
          <outline text="Brown stercobilin in stool"/>
          <outline text="Small amount becomes urinary urobilin"/>
        </outline>
        <outline text="Unconjugated excess not filtered into urine"/>
        <outline text="Conjugated excess: excretion failure, cholestasis">
          <outline text="Dark urine, pale stool"/>
        </outline>
        <outline text="Neonatal risk of kernicterus">
          <outline text="More production, immature conjugation, recycling"/>
          <outline text="Phototherapy makes excretable isomers"/>
        </outline>
      </outline>
      <outline text="Tyrosine and tryptophan products">
        <outline text="Phenylalanine hydroxylation forms tyrosine"/>
        <outline text="Catecholamines, thyroid hormones, melanin">
          <outline text="Tyrosine hydroxylase is rate-controlling"/>
        </outline>
        <outline text="Phenylketonuria disrupts brain development">
          <outline text="Early diet prevents intellectual disability"/>
          <outline text="Tetrahydrobiopterin defects need transmitter therapy"/>
        </outline>
        <outline text="Tryptophan forms serotonin, then melatonin">
          <outline text="Carcinoid diverts tryptophan: niacin deficiency"/>
        </outline>
      </outline>
      <outline text="Histamine, GABA, and nitric oxide">
        <outline text="Histidine decarboxylation forms histamine">
          <outline text="Allergy, gastric acid, wakefulness"/>
        </outline>
        <outline text="Glutamate decarboxylation forms GABA"/>
        <outline text="Arginine forms nitric oxide and citrulline">
          <outline text="Endothelial, neuronal, inducible isoforms"/>
          <outline text="Low cofactors uncouple, making superoxide"/>
        </outline>
      </outline>
      <outline text="Creatine, glutathione, and melanin">
        <outline text="Creatine from arginine, glycine, methyl group">
          <outline text="Creatine kinase buffers rapid energy demand"/>
          <outline text="Plasma creatinine reflects breakdown, kidney"/>
        </outline>
        <outline text="Glutathione: glutamate, cysteine, glycine">
          <outline text="Detoxifies peroxides, conjugates electrophiles"/>
          <outline text="Cysteine limits synthesis: N-acetylcysteine"/>
        </outline>
        <outline text="Tyrosinase starts melanin in melanosomes">
          <outline text="Albinism: multiple molecular disorders"/>
          <outline text="Vision affected via retinal development"/>
        </outline>
      </outline>
    </outline>
  </body>
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