Bio Chemistry

BIOCHEMISTRY 3(2+1)

Lesson 24 : Amino Acid Metabolism

Porphyrin Synthesis

1. First step in biosynthesis of porphyrins is condensation of glycine and succinyl CoA to form ? -aminolevulinate via ? -aminolevulinate synthase.


• Translation of mRNA of this enzyme is feedback-inhibited by heme


2. Second step involves condensation of two molecules of ? -aminolevulinate to form porphobilinogen; catalyzed by ? -aminolevulinate dehydrase.
3. Third step involves condensation of four porphobilinogens to form a linear tetrapyrrole via porphobilinogen deaminase.

This is cyclized to form uroporphyrinogen III.

4. Subsequent reactions alter side chains and degree of saturation of porphyrin ring to form protoporphyrin IX.
5. Association of iron atom creates heme; iron atom transported in blood by transferrin.
6. Inherited or acquired disorders called porphyrias are result of deficiency in an enzyme in heme biosynthetic pathway.
7. congenital erythropoietic porphyria - insufficient cosynthase (cyclizes tetrapyrrole)


• Lots of uroporphyrinogen I, a useless isomer are made
• RBCs prematurely destroyed
• Patient’s urine is red because of excretion of uroporphyrin I

Heme Degradation:

• Old RBCs are removed from circulation and degraded by spleen.
• Apoprotein part of hemoglobin is hydrolyzed into amino acids.
• First step in degradation of heme group is cleavage of ? -methene bridge to form biliverdin, a linear tetrapyrrole; catalyzed by heme oxygenase; methene bridge released as CO.
• Second step involved reduction of central methene bridge to form bilirubin; catalyzed by biliverdin reductase.
• Bilirubin is complexed with serum albumin --> liver --> sugar residues added to propionate side chains.
• 2 glucuronates attached to bilirubin are secreted in bile.

Jaundice

1. yellow pigmentation in sclera of eye and in skin --> excessive bilirubin levels in blood
2. Caused by excessive breakdown of RBCs, impaired liver function, mechanical obstruction of bile duct.
3. Common in newborns as fetal hemoglobin is broken down and replaced by adult hemoglobin.