Chapter 31 Quiz Flashcards
The heme of hemoproteins such as hemoglobin and the cytochromes is an iron-containing porphyrin consisting of four pyrrole rings joined by methyne bridges.
True
A total of eight methyl, vinyl, and propionyl substituents on the four pyrrole rings of heme are arranged in a specific sequence. The metal ion (Fe2+ in hemoglobin; Mg2+ in chlorophyll) is linked to the four nitrogen atoms of the pyrrole rings.
True
Biosynthesis of the heme ring involves eight enzyme-catalyzed reactions. Some of these reactions occur in mitochondria, others in the cytosol.
True
Synthesis of heme commences with the condensation of succinyl-CoA and glycine to form δ-aminolevulinate (ALA). This reaction is catalyzed by ALA synthase 1 (ALAS1), the regulatory enzyme of heme biosynthesis.
True
Synthesis of ALAS1 increases in response to a low level of available heme.
True
Certain drugs (eg, phenobarbital) indirectly trigger enhanced synthesis of ALAS1 by promoting synthesis of cytochrome P450, which depletes the heme pool.
True
A second
ALA synthase, ALAS2, is not regulated by heme levels or by drugs that promote synthesis of cytochrome P450.
True
Genetic abnormalities of seven of the eight enzymes of heme biosynthesis result in inherited porphyrias.
True
Erythrocytes
and liver are the major sites of expression of the porphyrias.
True
Photosensitivity and neurologic problems are common complaints. Intake of certain toxins (eg, lead) can cause acquired porphyrias. Increased amounts of porphyrins or their precursors can be detected in blood and urine, facilitating diagnosis.
True
Catabolism of the heme ring, initiated by the mitochondrial enzyme heme oxygenase, produces the linear tetrapyrrole, biliverdin. Subsequent reduction of biliverdin in the cytosol forms bilirubin.
True
Bilirubin binds to albumin for transport from peripheral tissues to the liver, where it is taken up by hepatocytes. The iron of heme is released and reutilized.
True
Mutations in the encoding gene result in reduced or
absent activity of bilirubin UDP-glucuronosyl transferase activity.
True
Clinical presentations that reflect the severity of the mutation(s) include Gilbert syndrome and two types of Crigler-Najjar syndrome, conditions whose severity depends on the extent of remaining enzyme activity.
True
Following secretion of bilirubin from the bile into the gut, bacterial enzymes convert bilirubin to urobilinogen and urobilin, which are excreted in the feces and urine.
True
