Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

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Chapter | 8 Porphyrins and the Porphyrias
TABLE 8-1 Erythrocyte Life Span of Animals
Determined by the Cohort Labeling of Heme
Animal Label Life Span
(Days)
Reference
Antelope
14
C 80 Cornelius et al . (1959)
Cat
15
N 77 Valentine et al . (1951)
“
14
C 66–79 Kaneko et al . (1966)
“
59
Fe 68 Brown and Eadie (1953)
“ “ 36–66 Liddle et al . (1984)
Chicken
14
C 20 Altland and Brace (1956)
Cow
14
C 135–162 Kaneko (1963)
Deer (Mule) “ 95 Cornelius et al. (1959)
Dog “ 86–106 Cline and Berlin (1963)
“
59
Fe 95–109 Finch et al . (1949)
Duck
14
C 39 Altland and Brace (1956)
Goat “ 125 Kaneko and Cornelius (1962)
Tahr Goat “ 160–165 “ “ “ “
Guanaco “ 225 Cornelius and Kaneko (1962)
Guinea Pig
59
Fe 83 Everett and Yoffey (1959)
Horse
14
C 140–150 Cornelius et al . (1960)
Human “ 120 Berlin et al . (1957)
“
15
N 127 Shemin and Rittenberg
(1946b)
Mouse
59
Fe 20–30 Burwell et al . (1953)
Pig “ 63 Jensen et al . (1956)
“
14
C 62 Bush et al . (1955)
Rabbit
15
N 65–70 Neuberger and Niven (1951)
“
59
Fe 57 Gower and Davidson (1963)
“
14
C 50 “ “ “ “
Rat “ 64 Berlin and Lotz (1951)
“ “ 68 Berlin et al . (1951)
“
59
Fe 45–50 Burwell et al . (1953)
Sheep “ 70–153 Tucker (1963)
“
14
C 64–118 Kaneko et al . (1961)
Bighorn “ 147 “ “ “ “
Karakul “ 130 “ “ “ “
Aoudad “ 60 and 170 Cornelius et al . (1959)
1 . δ-Amino Levulinic Acid
The initial step in the pathway of δ -aminolevulinic acid
(ALA) synthesis occurs in the mitochondria and involves
the enzymatic condensation of glycine with succinyl-CoA
to form ALA. This reaction requires vitamin B 6 as pyridoxal
phosphate, and it is the pyridoxal-phosphate-glycine
FIGURE 8-4 The synthetic pathway for protoporphyrin and heme. Note
the partitioning of the heme synthetic pathway between the mitochondria
and the cytosol. The circled numbers correspond to the enzymes listed in
Table 8-2.
complex that condenses with succinyl-CoA ( Gibson et al. ,
1958 , Kikuchi et al. , 1958 ). The requirement for pyridoxine
explains the pyridoxine responsive anemia of pyridoxine
deficiency because in the absence of pyridoxine, the
condensation cannot occur. The condensing reaction is
catalyzed by the enzyme ALA synthase (ALA-Syn). ALA-
Syn is the rate-controlling enzyme for heme synthesis
( Granick, 1966 ). ALA-Syn is induced by heme and is also
suppressed by negative feedback inhibition by heme. Thus,
the end product, heme, controls its own synthesis ( Granick
and Levere, 1964 ). The ALA is next transferred into the
cytosol ( Sano and Granick, 1961 ).
2 . Porphobilinogen
Two moles of ALA are next condensed to form the precursor
pyrrole, porphobilinogen (PBG) in the cytosol
( Cookson and Rimington, 1953 ). The enzyme ALAdehydrase
(ALA-D), an enzyme that is strongly inhibited
by lead, catalyzes this reaction. The activity of this enzyme
has been assayed in lead poisoning, and a reduced activity
is generally regarded as presumptive evidence of exposure
to lead.