Selected parameters related to work tolerance were measured in 31 adult subjects with hemoglobin (Hb) concentration from 2.5 to 14.0g/100ml. Work tolerance was closely related to Hb concentration (r=0.74) regardless of the adequacy of storage iron level. One male and six females with a mean Hb of 3.5g/100ml (27-55 years old) were studied before and 24hr after transfusing 570ml of whole blood. The mean maximal work load tolerated increased 83% within 24hr after transfusion in these seven subjects. Post-exercise venous blood lactate was markedly lower after transfusion. Work tolerance of these subjects within 24hr after transfusion was the same as in other subjects who had had the equivalent Hb level as the post-transfusion subjects presumably for at least several weeks. These data suggest that the decrement in work performance capacity in iron-deficient and anemic subjects is, in large part, a reflection of the level of anemia rather than other non-Hb related biochemical changes that could accompany prolonged iron deficiency anemia.

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The relative importance of hemoglobin (Hb) and non-Hb iron for physical work capacity was studied in 45 adult male and female subjects, with a range of Hb and serum iron levels. Maximal work capacity, heart rate, venous blood lactate and serum protein were measured before and after 1 week of treatment with Imferon, i.v. Even though some non-Hb related effects on parameters indicative of maximal work capacity were found, the main factor was Hb related. Subjects with low Hb-high serum iron worked longer than ones with low Hb-low iron. When the work performed was similar, the marginal Hb-low iron group had a higher blood lactate concentration than the high Hb-high iron and marginal Hb-high iron groups. The coefficient of correlation between serum iron and post-exercise lactate levels was -0.41 (p<0.05). Even though neither of these groups showed a Hb response within 1 week of iron treatment, the initial low serum iron groups had significantly lower heart rates at a given work load relative to subjects with high iron but with a similar Hb level. This occurred both at rest and during light to heavy exercise. These results suggest that a rather rapid benefit of iron treatment is gained in iron-deficient subjects with severe and moderate anemia which cannot be accounted for by Hb changes. Although the primary factor which affects the physical work capacity of iron-deficient anemic subjects seems to be the Hb level, there also seems to be a significant non-Hb related effect of iron treatment as well.

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The effects of a natural imbalanced diet on body maturity and brain composition of rats' offspring were studied from birth over the suckling period. Results were compared with those of a group of pups from mothers fed on a low protein diet and with pups from normal rats fed on a stock diet. Chemical maturity was measured as N/H₂O ratio. Pups from mothers fed on the imbalanced diet showed retarded chemical maturity at the time of birth and until 14 days of age in spite of growth progress; they grew without increasing in chemical maturity but approached the chemical maturity of controls at 30 days of age. The chemical maturity of the low-protein progeny was preserved in spite of severe growth arrest. Brain/body ratio was normal in both groups and was not correlated with chemical maturity during the perinatal period, as would be normal. In the brain, low weight, low lipids and a DNA concentration higher than normal were the characteristics of the pups of the imbalanced group from birth until 14 days of age but, at 30 days, brain composition was normal, although it weighed less than it should have done. The brain of the progeny from the low-protein group showed low weight, low lipids and protein, and the protein/DNA ratio was significantly lower until 9 days of age. At 14 days of age there remained severe growth arrest although the brain composition was approaching normal. There was a high mortality in this group and it was impossible to continue the experiment over the 30-day period. These findings confirm that if the mothers are fed on an essential amino acidimbalanced diet the brain and chemical maturity of the pups during the suckling period are affected in a different way when compared with low protein exposure, and confirmed the working hypothesis that protein quality plays a key role in development and that the effects of imbalanced diets cannot be merely ascribed to a relative protein deficiency.

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Histidine was found to be an activator of rabbit muscle pyruvate kinase activity with a K_1/2 value of 0.6mM. Carnosine and anserine are also effective, but only at much higher concentrations. Hyperbolic kinetics with phosphoenolpyruvate of the enzyme were found in either the presence or absence of histidine.
Of a number of divalent cations tested, only Zn²⁺ was found to be an effective inhibitor of enzyme activity at low concentrations. The kinetic data suggested that Zn²⁺ acted as inhibitor as well as activator for the enzyme activity; a high affinity binding site was associated with K_i of approximately 4.8μM Zn²⁺ and a catalytic site was associated with K_m of approximately 80μM Zn²⁺. Zn²⁺, which is associated to a high affinity binding site of the enzyme, was removed by the addition of histidine with a K_1/2 of approximately 0.6mM. From these findings, histidine including anserine and carnosine in muscle may act as a chelating agent for the enzyme activity.

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We investigated the effect and the fate of an extremely high amount of orally administered lactic acid in rats. The dosed amount of lactic acid, 390mg per 200g body weight (30 times higher than that normally detected in the stomach of rats), was determined from the results of observation of acute toxicity of lactic acid in rats. Six hours after the administration of excess lactic acid together with 10μCi of L-[U-¹⁴C]lactic acid and 10μCi of D-[U-¹⁴C]lactic acid, rats were sacrificed and the pH of the blood, the amount of lactic acid in each organ, L-lactate dehydrogenase (LDH) and some other enzyme activities and incorporation of radioactivities in each fraction of certain organs were measured. The control rats were given the labeled lactic acid and the same volume of water in place of cold lactic acid. Significant decrease of blood pH (ΔpH =0.14) and increase of blood lactic acid concentration (2-fold) were observed. However, these differences were no longer observed at 24hr after the administration. The amount of lactic acid degraded to expired CO₂ was 42.4% in the experimental group, whereas it was 61.3% in the control group. Radioactivities incorporated into protein and lipid fractions in the experimental group were higher than those in the control group, 3.8 and 4.9 times, respectively. It was suggested that an extremely high amount of orally administered lactic acid was utilized as an energy source, and that an excess of lactic acid was incorporated into protein and lipid in addition to degradation into CO₂.

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The nutritional significance of plasma free amino acids was examined by studying the effects of the quality and quantity of dietary protein on free amino acids in plasma and tissues of adult rats. The animals were given a diet containing 3, 6 or 10% egg protein or 3, 13 or 20% wheat gluten or rice protein for 4 weeks. At the end of the 4-week period, the rats were fasted for 12hr and the samples were prepared for the measurements of free amino acids in plasma and tissues. In rats on lowprotein diets, the plasma levels of essential amino acids (EAAs) decreased significantly, the reduction unexpectedly being greatest in rats on egg protein and least in those on wheat gluten. However, the levels of threonine, leucine and phenylalanine showed significant correlations with the dietary protein level, irrespective of the protein source. Moreover, the plasma lysine levels in rats on rice and wheat gluten diets were maintained at almost the normal levels, irrespective of the protein level, although lysine is a limiting factor in these proteins.
Of the nonessential amino acids (NEAAs), serine and glycine in the plasma increased greatly in rats on low-protein diets, and then the ratio of EAAs to NEAAs (E/N) decreased significantly to about half (0.44 to 0.47) the values in rats on the highest protein diets, irrespective of the protein source.
Findings in muscle were comparable to those in plasma. In liver, the ingestion of low-protein diets resulted in higher levels of serine and threonine, especially in groups on poor quality protein, while total EAAs were not affected by the dietary protein level. Unlike in the plasma and other tissues, in the small intestine tissue, free amino acids showed no consistent change in response to the dietary protein. It is suggested that this tissue contributes to correcting the amino acid pattern of the ingested protein.

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To elucidate the response of amino acid metabolism in the liver to dietary protein and plasma amino acids, the livers of adult rats fed on diet containing 10% (control) or 3% (low-protein) egg protein for 3 weeks were perfused for 120 min with amino acid-free medium in Experiment 1 or medium containing an amino acid mixture simulating that in plasma in Experiment 2. During perfusion about 40% of the free amino acids were lost from the liver in Exp. 1, and about 30% in Exp. 2. During this period, in Exp. l the releases of free amino acids and urea into the medium were 140μmol and 2.52mg, respectively, in the control group and 207μmol and 1.10mg, respectively, in the low-protein group. Thus release was greater than decrease in free amino acids in the liver. Essential amino acids, particularly lysine and branched chain amino acids, were released preferentially. The results suggest that the amount of breakdown of liver protein in the two groups was similar, but that the nitrogen was mainly released as free amino acids in the low-protein group, and as urea in the control group. On the contrary, in Exp. 2 the amount of nitrogen released from the liver was comparable to the decrease in amino acids in the liver, and the releases of urea were also less, being 1.83 mg in the control group and 0.54mg in low-protein group. The results show that amino acid metabolism in the liver is greatly affected by the nutritional state of the animal and the amino acid content of the perfusion fluid.

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