Benzoquinoneacetic acid, the quinone of homogentisic acid, given intraperitoneally to guinea pigs is distributed mainly into skin and cartilage, as found previously with homogentisic acid. I n contrast to homogentisic acid, benzoquinoneacetic acid reacts chemically with proteins and homogenates of skin and cartilage in vitro to give products which may be similar to those formed during the development of ochronotic pigmentation of the connective tissues in alcaptonuria. The physical and chemical events leading to ochronosis are discussed.
Acido benzoquinonacetic, le quinona de acido homogentisic, quando administrate per via intraperitonee a porcos de India, es distribuite principalmente in pelle e cartilagine, como il esseva previemente trovate in le caso de acido homogentisic. Per contrast0 con acido homogentisic, acido benzoquinonacetic reage chimicamente con proteinas e homogenatos de pelle e cartilagine in vitro resultante in le formation de productos que es possibilemente simile a illos formate durante le disveloppamento de pigmentation ochronotic del tissus conjunctive in alcaptonuria. Es discutite le evenimentos physic e chimic que resulta in le apparition de ochronosis.
LTHOUGH alcaptonuric individuals lack the enzyme homogentisic acid
A oxidase from birth,lS2 it is not until many years later that ochronosis, the pigmentation of the cartilage, tendons and other connective tissues appears, and it takes even longer, often several decades, before the degenerative arthritis of the spine and the large peripheral joints (ochronotic arthropathy ) is e ~i d e n t . ~. ~ Investigations on the biochemical mechanisms responsible for the production of ochronotic pigmentation of the connective tissues in alcaptonuria have been undertaken in our laboratory. A specific micromethod has been developed to determine homogentisic acid (HGA) in plasma" and other biological materiaL6 This method was employed to study the distribution of homogentisic acid after intraperitoneal injection in guinea pigs. It was found that skin and cartilage maintained higher concentrations of homogentisic acid than the other tissues.6 The affinity of the connective tissues for homogentisic acid suggests that physical binding to the connective tissues is the first event in the complicated process by which this acid is oxidized and polymerized to the melanin-like pigment. It is probable that the next step is the oxidation of homogentisic acid to its corresponding quinone, benzoquinoneacetic acid (BQA), which may then react chemically with the connective tissues.
In this paper we will present studies on the physiologic distribution of benzoquinoneacetic acid after its intraperitoneal injection into guinea pigs, and demonstrate that this quinone undergoes chemical interaction with various proteins and connective tissue preparations.