THE OCCURRENCE AND DETERMINATION OF δ-AMINOLEVULINIC ACID AND PORPHOBILINOGEN IN URINE

The heme-heme oxygenase system has recently been recognized to possess important regulatory properties. It is tightly involved in both physiological as well as pathophysiological processes, such as cytoprotection, apoptosis, and inflammation. Heme functions as a double-edged sword. In moderate quantities and bound to protein, it forms an essential element for various biological processes, but when unleashed in large amounts, it can become toxic by mediating oxidative stress and inflammation. The effect of this free heme on the vascular system is determined by extracellular factors, such as hemoglobin/heme-binding proteins, haptoglobin, albumin, and hemopexin, and intracellular factors, including heme oxygenases and ferritin. Heme oxygenase (HO) enzyme activity results in the degradation of heme and the production of iron, carbon monoxide, and biliverdin. All these heme-degradation products are potentially toxic, but may also provide strong cytoprotection, depending on the generated amounts and the microenvironment. Pre-induction of HO activity has been demonstrated to ameliorate inflammation and mediate potent resistance to oxidative injury. A better understanding of the complex heme-heme

Different faces of the heme-heme oxygenase system in inflammation

The glycine cleavage system catalyzes the following reversible reaction: Glycine + THF + NAD+ ⇌ 5,10-methylene-THF + + CO2 + NH3 + NADH Reversibility of the overall reaction was established through the studies with the enzymes prepared from liver mitochondria of rat and cock and from extracts ofArthrobacter globiformis grown on glycine. The glycine cleavage system is composed from four protein components. The four proteins were revealed to exist originally as an enzyme complex in the liver mitochondria. Partial reactions of glycine cleavage and glycine synthesis were studied in detail with partially purified individual protein components. Particularly a protein-bound intermediate of glycine metabolism could be isolated and its nature and role were clarified. A tentative scheme was presented to explain the whole process of the reversible glycine cleavage. The glycine cleavage system was shown to represent the major pathway of catabolism of both glycine and serine in vertebrates, including mammals, birds, reptiles, amphibians, and fishes. Serine catabolism in these animals proceeds mainly by way of the cleavage of serine to form methylene-THF and glycine rather than deamination by serine dehydratase. In ureotelic and ammonotelic animals methylene-THF formed from the α-carbon of glycine as well as theβ-carbon of serine could be further oxidized to CO2 in either the mitochondria or the soluble tissue fractions, while in uricotelic animals methylene-THF could hardly be oxidized to CO2 and instead, was utilized mostly for purine synthesis. Glycine synthesis by the glycine cleavage system did not appear to have appreciable physiological significance in animals.

The glycine cleavage system: composition, reaction mechanism, and physiological significance.

Mitochondrial coproporphyrinogen oxidase and protoporphyrin formation.

Charlotte S. Russell

Papers

δ-AMINOLEVULINIC ACID, ITS ROLE IN THE BIOSYNTHESIS OF PORPHYRINS AND PURINES1

The succinate-glycine cycle. I. The mechanism of pyrrole synthesis.

The succinate-glycine cycle. II. Metabolism of delta-aminolevulinic acid.

THE SYNTHESIS OF PROTOPORPHYRIN FROM δ-AMINOLEVULINIC ACID IN A CELL-FREE EXTRACT1