Delta-aminolaevulinic acid

In healthy people, forming haemoglobin for their erythrocytes and haem-dependent enzymes, the rate of haem synthesis is controlled by negative feedback according to the amount of haem present. When more haem is needed there is increased production of the rate-controlling enzyme delta-aminolaevulinic acid (ALA) synthase which provides the basis of the formation of porphyrin precursors of haem. But in people with porphyria one or other of the enzymes that convert the various porphyrins to haem is deficient and so porphyrins accumulate. A vicious cycle occurs less haem —> more ALA synthase —> more porphyrin precursors, the metabolism of which is blocked, and a clinical attack occurs. 

Chalevelakis G, Bouronikou H, Yalouris AG, Economopoulos T, AthanaseHs S, Raptis S. Delta-Aminolaevulinic acid dehydratase as an index of lead toxicity Time for a reappraisal Eur J Clin Invest 1995 25 53-8. 

S. Fijan, H. Honigsmann, B. Ortel (1995). Photodynamic therapy of epithelial skin tumors using delta-aminolaevulinic acid and desferrioxamine. Br. J. Dermatol, 133, 282-288. 

S.L. Gibson, D.J. Cupriks, J.J. Havens, M.L. Nguyen, R. Hilf (1998). A regulatory role for porphobilinogen deaminase (PBGD) in delta-aminolaevulinic acid (delta-ALA)-induced photosensitization Br. J. Cancer, 77, 235-243. 

N.I. Berlin, A. Neuberger, J.J. Scott (1956). The metabolism of delta-aminolaevulinic acid. 1. Normal pathways, studied with the aid of N, and 2. Normal pathways studied with the aid of C. Biochem. J., 64, 80-100. 

A. Jarrett, C. Rimington, D.A. Willoughby (1956). Delta-aminolaevulinic acid and porphyria. Lancet, i, 125-127. 

M.R. Moore, F.B. McGillion, A. Goldberg (1976). Some pharmacological and behavioral effects of delta-aminolaevulinic acid. In M. Doss (Ed.). Porphyrins in Human Diseases (pp. 148-154). Karger, Basel. 

T. Henta, Y. Itoh, M. Kobayashi, Y. Ninomiya, A. Ishibashi (1999). Photodynamic therapy for inoperable vulval Paget s disease using delta-aminolaevulinic acid successful management of a large skin lesion. Br. J. Dermatol., 141, 347-349. 

A.M. Wennberg, L.E. Lindholm, M. Alpsten, O. Larko (1996). Treatment of superficial basal cell carcinomas using topically applied delta-aminolaevulinic acid and a filtered xenon lamp. Arch. Dermatol Res., 88, 561-564. 

C. Fritsch, P. Lehmann, W. Stahl, K.W. Schulte, E. Blohm, K. Lang, H. Sies, T. Ruzicka (1999). Optimum porphyrin accumulation in epithelial skin tumors and psoriatic lesions after topical application of delta-aminolaevulinic acid (Review). Br. J. Cancer, 79(9-10), 1603-1608. 

The other indirect measures which can be used to monitor lead exposure are changes in the levels of a range of enzymes and metabolites involved in the synthesis and operation of haem. Thus, increases in the levels of free erythrocyte protoporphyrin (FEP) or of zinc protoporphyrin (ZPP) in blood can be associated with increased levels of lead in blood, as can decreased levels of activity of the enzyme delta-aminolaevulinic acid ddiydratase (ALAD). Similarly increases in the levels of urinary coproporphyrin (CP) and urinary aminolaevulinic acid (ALAU) also reflect increased lead exposure. These measures are not, however, always reliable since they can be affected by other factors, for exattqrle ZPP may be increased by iron deficiency. Measurements of these parameters tend, therefore, to be us only in conjunction with, and to provide supplementary data to, blood lead measurements. 

Meredith PA, Moore MA, Goldberg A (1977) Effects of aluminium, lead and zinc on delta-aminolaevulinic acid dehydratase. Enzyme 22 22-27 Mertz LM, Horn VJ, Baum BJ, Ambudkar IS (1990) Calcium entry in rat parotid acini activation by carbachol and aluminum fluroride. Am J Physiol 258 C654-C661... 

When referring to the early or subcriticaL effects of lead in humans as biological indicators of exposure, the primary concern is the alterations in those levels of intermediates in the haem biosynthesis pathway that are known to be affected by the presence of lead. Three processes that have lent themselves to examination in the context of biological monitoring include (1) the inhibition of delta-aminolaevulinic acid dehydratase (5-ALA-D) ... 

Measurement of blood lead levels and other biological indices of lead exposure were carried out annually. These other biological indices are blood delta-aminolaevulinic acid concentrations, the activity of ALA dehydratase in blood, and erythrocyte protoporphyrin concentrations. In addition, deciduous tooth lead concentrations will be measured. 

An interesting and unusual adverse effect attributed to pyrazinamide was described in a paper from the United States (54 ). A patient was described who suffered several attacks of acute intermittent porphyria whilst under treatment for tuberculosis. The first attack occurred after 18 months therapy with isoniazid and ethambutol. The second episode occurred after 14 days treatment with rifampicin, 7 days treatment with pyrazinamide and 3 days treatment with streptomycin. The patient was subsequently treated successfully with a combination of rifampicin, ethambutol and capreomycin. The compounds were investigated for their capacity to induce hepatic delta-aminolaev-ulinic acid synthesis in an in vitro preparation of rat Uver. The results showed that pyrazinamide had a greater potential for inducing the enzyme activity than any of the other compounds. It is worthy of note, however, that in this in vitro system para-aminosalicylic acid, rifampicin, cycloserine and ethionamide all induced increased delta-aminolaevulinic acid synthesis. 

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