Garrod, Archibald

In an address before the British Medical Association in 1914,(1) Archibald Garrod proposed that enzymes were... 

In Alexander G. Bearn Archibald Garrod and the Individuality of Man Chapter 3 (p. 25)... 

B. Childs. 1970. Sir Archibald Garrod s conception of chemical individuality A modem appreciation/V. Engl. J. Med. 282 71-78. (PubMed)... 

Alkaptonuria was the first condition known to be caused by a metabolic enzyme deficiency, hi 1902, Sir Archibald Garrod studied newborns whose urine turned black shortly after urination. The black color was due to oxidation in the urine of homogenistic acid, which accumulates because of a deficiency of the en me homogen-tisate dioxygenase. Fortunately, the urine discoloration is not detrimental to people with this lEM however, alkap-tonurics do tend to develop arthritis later in life. 

Garrod, A. E. (1909) Inborn Errors of Metabolism, Oxford, London Bearn, A. G. (1993) Archibald Garrod and the Individuality of Man, Oxford, New York... 

Knox W (1958) Sir Archibald Garrod s inborn errors of metabolism. Am J Hum Genet 10 3-32... 

Alkaptonuria is another disease of intermediate metabolism of aromatic amino acids. It was the first of a group of diseases discovered by Sir Archibald Garrod [84] called inborn errors of metabolism. The transformation of homogentisic acid into maleylacetoace-tate is blocked in alkaptonuria. Direct evidence for the location of the metabolic block was obtained by researchers who demonstrated a specific enzymatic block in the liver of alkaptonurics. These studies also indicated that the metabolic block was due to an absence of the enzyme rather than to the presence of an inhibitor or the lack of a cofactor. Consequently, whereas the urine of normal individuals contains no homogentisic acid (the renal threshold for that compound is low in both normal and diseased individuals), large amounts are recovered from the urine of alkap-tonuric patients, and the amount excreted parallels the patients protein and tyrosine intake. 

Cystinuria is a hereditary disease characterized by the excessive excretion of cystine, lysine, ornithine, and arginine in the urine, probably resulting from a deficiency in the renal tubular transport mechanism. Sir Archibald E. Garrod postulated that cystinuria resulted from a metabolic block involving the oxidation of cystine to sulfate. Later investigations of the pathogenesis of cystinuria demonstrated that the hereditary deficiency does not involve a metabolic block. If a metabolic impairment existed, cystine would be expected to accumulate in the plasma of cystinurics, but plasma levels of cystine are normal or low in cys-... 

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