Liver cell, heme biosynthetic enzymes

The basic concept upon which ALA-PDT is based was conceived as we studied the biochemical basis for the group of metabolic diseases known as the porphyrias [43]. Some of the porphyrias are associated with a generalized photosensitization which is caused by the accumulation of specific types of porphyrin in the blood and/or tissues, where each type of porphyrin accumulates as the result of a specific abnormality in the biosynthetic pathway for heme. Although at that time it was generally believed that the expression of such abnormalities was restricted to the liver and the hemopoietic system (those tissues which synthesize large amounts of heme), it was obvious that all nucleated cells must have at least some capacity to synthesize heme because they all use heme-containing enzymes for the tricarboxylic acid cycle. 

Chick embyro liver cells in primary culture can be used in a sensitive test to determine the drugs or chemicals that can induce hepatic porphyria. The compounds are incorporated into the growth medium at a concentration of 0.5 to 100 xg/ml. The cells are examined 18 to 20 hours afterward with a fluorescence microscope. Granick [24,25] found that the inducing substance induce a de novo synthesis of ALA-synthe-tase, the limiting enzyme of the heme biosynthetic chain. As a result, ALA is greatly increased and is converted in part into porphyrins which are visualized as red fluorescent material in the cytoplasm of individual hepatic cells. 

C. Localization of Enzymes of the Heme Biosynthetic Chain in the Liver Cell... 

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