The biochemistry of copper deficiency I. Enzymological disturbances, blood chemistry and excretion of amino-acids

Abstract

The biochemistry of an uncomplicated deficiency of copper is studied. A moderate to advanced depletion of copper does not affect the activity or level of the following: liver-slice respiration, tricarboxylic acid cycle, fatty-acid oxidation, amino-acid oxidation, oxidative phosphorylation, anaerobic glycolysis, catalase, DPN-cytochrome c reductase, transmethylase, choline oxidase, isocitric dehydrogenase, succinic dehydrogenase, malic dehydrogenase, glutamic dehydrogenase, oxidation of glucose and pyruvate by brain mitochondria, urinary amino-acids, plasma protein, magnesium, calcium, sodium, potassium, or inorganic phosphate. Activities of cytochrome oxidase and succinoxidase are reduced at this stage of deficiency. The loss of succinoxidase activity is due to the depletion of cytochrome oxidase which is severe and progressive from a very early stage of deficiency. Haem $\alpha $ is almost completely absent from copper-deficient tissues, and it is suggested that this is the limiting component of the cytochrome oxidase system. Mitochondria from deficient rats are very susceptible to 'ageing'. The 'ageing' effect is shown to be due to loss of and reversed by addition of the pyridine nucleotides, glutathione and manganese. The susceptibility to 'ageing' is thought to be secondary to an impaired synthesis of phospholipid. Extreme copper deficiency leads to a grave loss of the capacity of mitochondria to oxidize any substrate; this is almost certainly due both to the negligible activity of cytochrome oxidase and an acceleration of the effect of 'ageing'. Isocitric dehydrogenase activity is increased and DPN-cytochrome c reductase decreased at this stage; the reasons are discussed.