Tissue-Specific Regulation of Iron Metabolism and Heme Synthesis: Distinct Control Mechanisms in Erythroid Cells

The enzymes responsible for chlorophyll biosynthesis in plants, algae and cyanobacteria are identified and described, with emphasis on their protein composition and structure, required cofactors, physical and catalytic properties, protein-protein interactions and allosteric modulation of activity. Properties and features of the pathway that enable it to operate in a coordinated way while using unstable and light-sensitive intermediates in potentially hostile biochemical environments are discussed. The evolutionary relationships and possible origins of the chlorophyll biosynthetic enzymes are also discussed.

Enzymes of chlorophyll biosynthesis

Increase in Activity of δ-Aminolevulinic Acid Synthetase in Liver Mitochondria Induced by Feeding of 3, 5-Dicarbethoxy-1, 4-dihydrocollidine

Biological formation of pyrroles: nature's logic and enzymatic machinery.

Mitochondrial coproporphyrinogen oxidase and protoporphyrin formation.

The enzymatic synthesis of delta-aminolevulinic acid.

However, the details of this condensation and the mechanism were not known. This communication reports our finding that particle-free extracts of two photosynthetic bacteria, Rhodopseudomonas spheroides and Rhodospirillum. rubrum, are capable of catalyzing the net synthesis of 6-aminolevulinic acid from succinate and glycine on addition of cofactors, including coenzyme A, adenosine triphosphate (ATP), pyridoxal phosphate, and Mg* ions, or from succinyl-coenzyme A and glycine on addition of pyridoxal p h o ~ p h a t e . ~ Laver and Neuberger6 and Gibson et uL7 recently reported that a particulate fraction obtained from erythrocytes of chickens treated with phenylhydrazine was capable of synthesizing this compound from a-ketoglutarate and glycine and from succinylcoenzyme A and glycine. LascellesR has demonstrated that not only are porphyrins synthesized by I<. splzeroides by the sequence of events previously elucidated in other cells, but also that porphyrins and porphobilinogen accumulate in the medium. We were encouraged to investigate this bacterium for the enzymes responsible for the synthesis of 6-aminolevulinic acid, for we found that this acid was also present in the medium after the cells were suspended in medium I of Lascelles. R. spheroides and R. rubrum were grown under anaerobic conditions in the light. The bacteria were harvested by centrifugation and washed with saline, and then 0.1 RZ phosphate buffer extracts of the broken cells were centrifuged at 105,000 g for different lengths of time. I t ran be seen in TABLES 1 and 2 that the extracts of both R. spheroides and R. rubrum synthesized 6-aminolevulinic acid from succinate and glycine and that there is a marked dependency for pyridoxal phosphate, CoA, ATP and hIg++ ions especially in the dialyzed extracts. It also can be seen (compare TAHXS 1 and 2) that whereas extracts of R. spheroidcs obtained on centrifugation for 30 min. synthesize a fair amount of porphyrin from the formed 6-aminolevulinic acid, little synthesis occurred in those extracts obtained on a 3-hour centrifugation. The crude extracts of R. rubrum are not as dependent on the addition of CoA as are those of R. spheroides. However, it can be seen in TABLE 3 that extracts

Goro Kikuchi

Papers

The enzymatic synthesis of delta-aminolevulinic acid.

ENZYMATIC SYNTHESIS OF δ‐AMINOLEVULINIC ACID*