Effects of Chronic Ascorbic Acid Deficiency on Guinea Pig Lysosomal Hydrolase Activities

Abstract

Previously we have observed increased specific activities of several lysosomal hydrolases in scorbutic guinea pigs and thus the specificity of this effect was examined in guinea pigs marginally deficient in ascorbic acid (AA). Guinea pigs were fed an AA-deficient diet for 2 weeks to deplete body AA pools and then fed a stock diet containing 0.5 mg AA/g diet or the deficient diet plus oral administration of 10 mg AA/day, 1 mg AA/100 g body weight or 0.5 mg AA/100 g body weight each day. Animal were periodically killed during the 12-week experiment and lysosomes isolated from individual livers and analyzed. Serum and brain AA declined when AA was withheld, returned to normal when the stock diet or 10 mg AA were fed but remained at low levels on administation of 1.0 mg or 0.5 mg AA/100 g body weight. Brain norepinephrine followed a similar pattern to brain AA and was opposite to the pattern observed for dopamine. In guinea pigs receiving 1 mg AA/100 g body weight, amine concentrations slowly returned to normal after 8 weeks. Serum hexosaminidase and lysosomal cathepsins A and B were unchanged during the experiment, whereas lysosomal hexosaminidase and acid phosphatase were significantly higher when the experiment was terminated.

Mood improvement in young adult males following supplementation with gold kiwifruit, a high-vitamin C food

“…It also acts as a cofactor for the enzyme dopamine β-hydroxylase that converts dopamine into the neurotransmitter noradrenaline ( 45 ) . Brain noradrenaline levels are decreased in vitamin C-deficient guinea-pigs ( 46 , 47 ) and depletion is associated with depressive symptoms in humans ( 48 ) . Vitamin C also serves to activate the enzyme tyrosine hydroxylase via recycling its cofactor tetrahydrobiopterin, which is required for the conversion of l -tyrosine to the dopamine precursor l -DOPA ( l -3,4-dihydroxyphenylalanine) ( 49 ) .…”

Vitamin C deficiency increases basal exploratory activity but decreases scopolamine-induced activity in APP/PSEN1 transgenic mice

“…However, differing patterns of activity between supplementation groups may reflect differences in striatal or accumbens dopamine induced by varying brain vitamin C levels. Vitamin C is an essential co-factor in the synthesis of norepinephrine from dopamine and vitamin C deficiency in guinea pigs has been shown to increase brain dopamine level in proportion to the change in brain ascorbate (Deana et al, 1975; Hoehn and Kanfer, 1980; Saner et al, 1975). Vitamin C is released in the striatum with behavioral activation (O'Neill and Fillenz, 1985) and both locomotor activity and vitamin C release increase in response to dopamine agonists (Pierce and Rebec, 1990).…”

Vitamin C function in the brain: vital role of the ascorbate transporter SVCT2

“…However, there does not appear to be any clear relationship between extracellular ascorbate levels and any neurotransmitters, and the question as to how such modulation is achieved has yet to be clarified. Ascorbate deficiency in guinea pigs is associated with significant increases (∼25%) in dopamine levels and similar relative decreases in norepinephrine [140], presumably because normal amounts of dopamine could not be metabolized into norepinephrine by dopamine β-hydroxylase in the absence of ascorbate as an essential co-factor. In the animals with the most severe ascorbate deficiency, neurotransmitter levels never normalized.…”