A perfusion technique was utilized to assess the rate of absorption and metabolism of L-methionine by livers isolated from rats fed a diet deficient in zinc. The endogenous concentration of S-adenosyl-L-methionine in the livers from the zinc-deficient rats was near normal, while the concentration in pair-fed controls was approximately 50% of that found in normal livers (ad libitum fed). The rate of uptake of methionine by the livers isolated from zinc-deficient rats was significantly less than in the pair-fed or ad libitum-fed controls. The synthesis of L-methionine, S-adenosyl-L-homocysteine and S-adenosylmethionine was not impaired in the livers from the zinc-deficient rats. However, the methyl group of the S-adenosylmethionine turned over much more slowly in the livers from zinc-deficient rats than in either control group. This was reflected in the depressed rates of methylation of various macromolecules, particularly DNA and histones. The synthesis of nuclear proteins (histones and nonhistone chromosomal proteins) was depressed in the livers from zinc-deficient rats. The reduced synthesis of chromosomal proteins and marked reduction in DNA methylation would be consistent with the finding that DNA biosynthesis and cellular proliferation are markedly depressed in zinc-deficient animals.

1. Levels of zinc in liver and plasma of the Zn-depleted rats fluctuated with the feeding cycle and were significantly higher at the bottom than at the top of the cycle. As Zn deficiency became more severe fluctuations in plasma Zn diminished. Concentrations of Zn in liver, in contrast to levels in plasma and femur, were not markedly lowered by day 15. 2.In contrast to udlib.-fed (AL) and overnight-fasted (OF) controls, some pair-fed (PF) controls had elevated levels of Zn in liver and plasma.3. Intakes of water and food were sigdicantly correlated in Zn-deficient rats. Packed cell volumes were significantly higher for Zn-depleted than for AL and PF rats.4. Food intakes and plasma glucose concentrations were related in AL, OF and PF control rats but not in Zndeficient rats. At day 15of Zn deficiency the order of total plasma amino acid concentrations in the groups of rats was AL > Zndeficient > OF > PF. Many of the differences between the AL and OF groups for individual plasma amino acids also appeared in the Zn-deficient group at the top and bottom of the feeding cycle. Differences in individual amino acid conmntrations at the top and bottom of the feeding cycle tended to be opposite in the PF and the Zn-ddicient group. Levels of tyrosine and tryptophan in plasma were correlated (P < 0.05) with the cyclic feeding pattern of the Zn-deficient group; however, the ratios tryptophan or tyrosine: sum of other large neutral amino acids did not correlate significantly with the eating habits of Zndeficient rats.

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