The Saturation Kinetics Model (SKM) is useful in describing many physiological responses as functions of a limiting dietary nutrient. However, as nutrients are fed at higher dietary concentrations, responses become inhibited and diminish from their usual plateaus. By adding an inhibition constant (Ks) to the SKM in a manner consistent with substrate inhibition (based on enzyme kinetics), it becomes possible to predict the inhibited portions of the nutrient-response curve. To test this, rats were fed diets of graded levels of casein (0-75%) or lysine (0-6.2%), and weight gains and food intakes were measured daily for up to 2 wk. The inhibition form of the SKM was able to predict the complete response range of each experiment, producing a Ks (weight gain) at a dietary level of 50.60% for casein and 7.56% for lysine. It was also possible to set up an upper and lower dietary nutrient concentration that encompassed the 100% response range for each response, thereby giving an inhibition or toxicity index of 2.02 for casein and 4.98 for lysine. This index allows one to set nutritional requirement levels precisely, optimizing responses without moving into inhibiting or toxic ranges of nutrients. Based on growth response curves, requirements were 25.61% for casein and 1.97% for lysine.

Daily weight gains and food intakes were measured in male, 120-g rats fed graded levels of dietary casein. After 14 d, serum and brain amino acid concentrations were measured. All physiological responses were tested for a functional relationship to dietary casein concentration. Food intake, weight gain and many serum amino acid profiles were shown to be saturable functions of percent casein in the diet. In general, essential amino acids increased in serum with increasing dietary casein concentration while nonessential amino acids decreased with increasing dietary casein concentration. Brain amino acid concentrations were shown to be linear functions of serum levels with the exceptions of phenylalanine and the acidic amino acids. Most amino acids showed a smaller range of values in brain than in serum. The exceptions were the levels of threonine, glutamine, serine and histidine, which were three times greater in brain than in serum. Brain levels of the neutral amino acids tryptophan and tyrosine were highly correlated with the amino acid/neutral amino acid ratios in serum, whereas leucine was negatively correlated. Brain histidine, which was inversely correlated with dietary casein, was found to correlate with specific food intake patterns. The four-parameter mathematical model for physiological responses was able to predict all the observed saturation type responses in the experiment.

these preliminary findings suggest that platelet measures of the traditional biomarkers for AD are feasible in the periphery. The measures of platelet APP-N and Ig, in particular, merit further study in a larger cohort of AD and control subjects.

Histidine (His) is elevated in plasma and brain during protein deficiency as well as in several pathological conditions, leading to the possibility of a direct effect on central nervous system (CNS) function. In this study, groups of weanling rats were fed diets containing graded levels of casein or a single indispensable amino acid (IAA: Leu, Val, Ile, Phe, Trp, Thr, Met or Lys) in order to produce nutritionally-deficient states. Body weight gains and food intakes were recorded daily for 2 wk. Whole brain and serum samples were obtained and analyzed for amino acid (AA) content. All weight gain and food intake responses could be predicted by the Saturation Kinetics Model. The only consistent pattern observed in AA profiles which could be correlated with food intake was an increase in brain His concentrations. Limiting dietary casein or IAA elevated brain His above controls 2.5- and 1.5-fold, respectively. Food intake was generally depressed by 50% at brain His concentrations above 105 nmol/g. Since His is the precursor of the depressant neurotransmitter histamine (HA), systemic increases may be significant in that HA could be a possible cause of the anorexia observed in protein and IAA deficiency.