Updated: 1/31/2020

Heme Metabolism

0%
Topic
Review Topic
0
0
N/A
N/A
Questions
4 4
0
0
0%
0%
Evidence
4 4
0
0
0%
0%
Videos
2 2
Heme sythesis
  • Functions 
    • hemoglobin
    • cytochrome b4
    • P450
  • Location of synthesis
    • involves both the mitochondria and the cytosol
    • occurs in nearly every cell
      • occurs in RBC progenitor cells
        • CANNOT occur in RBCs because they lack mitochondria
  • Pathway
    • ALA synthase is rate limiting enzyme (see above)
  • Deficiencies in heme synthesis
    • hemin
      • occurs when Fe3+ is incorporated instead of Fe2+
    • porphyria 
      • causes
        • symptoms due toxic accumulation of pathway intermediates
          • aminolevulinic acid (ALA) causes neurological symptoms
          • protoporphyrins cause photosensitivity
            • conjugated structure what absorbs light energy and forms free radicals
        • symptoms worsened by
          • sunlight
          • P450 inducing drugs
            • stimulate the heme synthesis pathway to ↑ production
            • ex.) barbiturates, alcohol
      • treatment
        • limit exposure to sun and P450 inducing substances
        • hemin
          • inhibits new heme production
      • types
        • porphyria cutanea tarda
          • deficiency in uroporphyrinogen decarboxylase 
          • AD
          • late onset (4th or 5th decade)
            • symptoms often noticed with alcohol consumption
          • presentation
            • photosensitivity
            • hyperpigmentation
              • body's attempt to protect the skin
            • dark red/brown colored urine
        • acute intermittent porphyria
          • deficiency in porphobilinogen deaminas
          • AD
          • late onset
          • presentation
            • NO photosensitivity
            • episodic psychological symptoms (paranoia, anxiety, depression)
            • vague abdominal pain
              • patients can present with a history of laparoscopies
            • dark red/brown colored urine
              • ALA and porphobilinogen (PBG) present in urine during symptoms
    • poisoning
      • lead
        • induced deficiency in ALA dehydratase and ferrochelatase
          • both enzymes are Zn2+ dependent metalloenzymes
          • Pb2+ replaces the Zn2+ at the active site
        • presentation
          • ↓ in IQ
          • microcytic anemia with coarse basophilic stippling
          • abdominal pain
          • ↑ in ALA without ↑ in PBG
            • differentiates from porphyrias
          • lead lines in bone and teeth xrays
          • nephrotoxicity
            • deposition in nuclei of proximal renal tubular cells
      • hexachlorobenzene
        • induced deficiency in uroporphyrinogen decarboxylase
        • presentation
          • hypertrichosis (↑ body hair coverage)
        • found in (now banned in USA) pesticides
    • iron deficiency
      • iron incorporated in the final step
      • result is microcytic hypochromic anemia
      • see Trace metals topic
    • vitamin B6 deficiency
      • rate limiting enzyme (ALA synthase) requires
      • most commonly due to isoniazid therapy
      • see Vitamins topic
Degradation of Heme
  • Function
    • rid body of hemoglobin removed from degraded RBCs
  • Location of degradation
    • spleen
      • site of RBC destruction
    • liver
      • site of bilirubin conjugation
    • intestine
      • conversion by normal gut flora
  • Pathway  
Bilirubin
  • Properties
    • insoluble
      • must travel in blood bound to albumin
    • conjugation
      • direct (conjugated)
        • glucuronate group added
          • soluble
      • indirect (unconjugated)
        • glucuronate group not yet added
          • insoluble
  • Modified forms
    • urobilinogen
      • gives urine yellow color
    • stercobilin
      • gives feces brown color
        • with a blocked bile duct no stercobilin in feces and it is clay colored

ces

 

Please rate topic.

Average 4.8 of 10 Ratings

Questions (4)
Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK
Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK
Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK

(M1.BC.14.7) A young man with history of seizure disorder is seen in the ED with complaints of confusion and stomach pain. His seizures are currently being treated with phenytoin. After talking with the patient you examine a urine sample (Figure A). You suspect he has a deficit in which of the following enzymes? Tested Concept

QID: 100072
FIGURES:
1

Pyruvate dehydrogenase

16%

(6/37)

2

Phosphofructokinase

0%

(0/37)

3

Glucose-6-phosphatase

14%

(5/37)

4

Porphobilinogen deaminase

43%

(16/37)

5

Uroporphyrinogen decarboxylase

27%

(10/37)

M 2 E

Select Answer to see Preferred Response

Evidence (4)
VIDEOS (2)
Topic COMMENTS (20)
Private Note