544 XI. HEMOGLOBIN CATABOLISM, I 



feces. Myohemoglobin, when destroyed in the muscle, may there- 

 fore undergo a more thorough decomposition than hemoglobin or 

 myohemoglobin in the blood (c/. 2162). 



There is, however, evidence that myohemoglobin in the muscle is 

 certainly more stable than hemoglobin. In anemias caused by 

 hemorrhage or lack of iron and copper no decrease of myohemoglobin 

 in the muscle occurs (507,917). It is also not converted into myohemo- 

 globin by nitrite or m-dinitrobenzene (1527). The fact that Meldolesi 

 and Siedel isolated only 30 mg. of mesobilifuscin from 100 feces of 

 myopathics also indicates that the metabolism of myohemoglobin is 

 very slow (cf. also the experiments of Hawkins and Whipple, 1196, 

 quoted in Section 2.2.1.). 



8. BILIRUBIN 



8.1. Quantitative Transformation of Prosthetic Group 

 of Hemoglobin to Bile Pigment 



Earlier attempts to determine how much of the prosthetic group 

 of hemoglobin is converted into bilirubin when hemoglobin is broken 

 down gave contradictory results, since neither the method of measur- 

 ing hemoglobin breakdown nor that of determining bile pigment were 

 adequate. Only the development of the technique of Whipple (3057, 

 3059) ultimately supplied the answer. Dogs with renal bile fistulae 

 are kept on a salmon-bread diet with iron-free salt mixture which 

 allows only a small degree of extra hemoglobin synthesis (1-3 g. 

 hemoglobin per week). They are constantly bled to keep up a certain 

 level of anemia (about one-third of the normal hemoglobin). The 

 iron reserves of the body are thus exhausted in 2 to 3 weeks, and the 

 dogs then may be kept constantly for several months on a steady 

 anemia level, before the experiments are performed. If the dogs are 

 fed bile acids they remain healthy for many years. Estimation of 

 the newly formed hemoglobin is carried out by measuring the amount 

 of blood which must be withdrawn in order to maintain the anemia 

 level. Bile pigments are determined in the combined bile and urine 

 by the oxidation method (cf. Chapter IV, Section 9.1.). This method 

 also includes biliverdin. 



Even under these conditions of the maximum effort of the body to 

 prevent anemia, 80-100% of the prosthetic group of hemoglobin is 

 excreted as bile pigments (516,1193,1195). 



