Max Kleiber

Metabolic turnover rate: A physiological meaning of the metabolic rate per unit body weight

Abstract In analogy to “specific gravity” or “specific heat” the expression “weight specific metabolic rate” (Ultsch, 1973) would be correct if the metabolic rate were directly proportional to body weight. In that case the quotient metabolic rate divided by body weight would be a constant, independent of body weight like density or specific heat are constants. The metabolic rate, however, is not proportional to body weight but to its 3 4 power. I have stated that heat flow per unit body weight has no proper physical or physiological meaning (Kleiber, 1970) , but since found such a physiological meaning: in work with tracers turnover rates are measured as quotients of transfer rates/pool content. For similometric animals pool contents are proportional to body weight. For such animals therefore the quotient metabolic rate/body weight may have a proper physiological meaning, namely the turnover rate of chemical energy in the animal body. The usefulness of the turnover rate is limited. For the calculation of the energy requirement of horizontal animal locomotion, for example, the calculation from the metabolic rate per animal is preferable to the calculation based on the metabolic rate per unit body weight.

Milk fat synthesis from acetate in mammary gland of the cow.

Summary 1. 2-C14 labeled acetate was injected into the milk cistern of the right front quarter of a lactating cow. This quarter was subsequently milked separately from the other 3 quarters and radioactivities of milk fat constituents from each were determined. 2. The data confirm that there is a delay of several hours between synthesis and secretion of milk fat. 3. A surprisingly small amount of the injected acetate diffused into the other 3 quarters or into the rest of the body. This can be accounted for by its rapid utilization for milk synthesis near the site of injection. 4. Fatty acids of all chain lengths and glycerol seem to be synthesized from acetate in the mammary gland itself. The glycerol synthesis, however, is on a smaller scale.

Glucose as a precursor of milk constituents in the intact dairy cow

Abstract 1. 1. Glucose uniformly labeled with 14 C was injected into the jugular veins of two normal lactating dairy cows as single doses of 3 and 6 microcuries per kg body weight respectively. The injected glucose, about 1 gram, amounted to less than 10% of the plasma glucose. 2. 2. Between 30 and 40 minutes after injection the radioactivity of the respiratory CO 2 reached a maximum of 9 microcuries per unit of the relative injected dose (μc injected per kg body weight). 3. 3. During the first 3 hours after injection of uniformly labeled glucose less 14 C appeared in the respiratory CO 2 than was expired during the corresponding period in earlier trials after injection of 14 C labeled acetate, propionate, or butyrate. 4. 4. More than 50% of the 14 C injected as uniformly labeled glucose appeared in the organic constituents of the milk within 10 hours after injection. Over 80% of this 14 C in milk components was found in lactose. 5. 5. In the first milk sample, 3 hours after injection, the specific 14 C activity in the components of the milk decreased in the following order: Lactose → Citrate → Casein → Milk fat. 6. 6. Only about 1% of the carbon transferred from plasma glucose to lactose passed the carbonate pool, 4 to 10% of the carbon transfer to casein followed this path. 7. 7. Three hours after injection the specific 14 C activity in blood glucose had decreased to about 1% of its theoretical level at the time of injection, the latter calculated from injected dose, plasma volume and glucose level in plasma. 8. 8. About 4 5 of the lactose carbon came from carbon in plasma glucose or a pool in rapid exchange with plasma glucose, 1 5 of the carbon in citrate originated from this pool and about 5% of the carbon in casein and milk fat.

Acetate as a precursor of amino acids of casein in the intact dairy cow.

Five lactating dairy cows were injected intravenously with acetate-I-14C or acetate-2-14C. Eight amino acids, recovered from casein collected at 3, 10, 22, and 34 hours after acetate-14C injection, were assayed for carbon-14. Carbon from acetate was transferred most efficiently to glutamic and aspartic acids and in lesser amounts to alanine, serine, glycine, proline, and arginine. Lysine did not contain significant amounts of 14C. The labeling of amino acids from acetate-14C differed markedly from that previously observed for glucose-14C. Carbon from uniformly labeled glucose was transferred most efficiently to alanine and serine and in smaller amounts to glutamic and aspartic acids, glycine, proline, and arginine. The specific activities of alanine, serine, and lactose were quite similar after acetate-14C injection suggesting a close relationship between the precursors of the three carbon amino acids and lactose. The distribution of 14C among the amino acids formed by the intact cow was consistent with results that would be expected if the TCA cycle and the glycolytic pathway were the pathway for transfer of carbon from acetate to amino acids of casein.

Body Size and Metabolism of Liver Slices in vitro.

Summary The metabolic rates of liver slices from rats, rabbits, sheep, one horse and one cow have been measured in vitro. These metabolic rates per unit tissue weight for rat, rabbit and sheep liver decrease systematically and significantly with increasing body size. The metabolic rate per unit tissue weight is inversely proportional to the 4th root of body weight. Body size affects thus the metabolic rate in vitro in the same way as it affects the metabolic rate of the intact animal and the factors which determine the metabolic level in vivo seem still to be present in the surviving tissues cut out of the organism.

Glucose as a precursor of amino acids in the intact dairy cow.

Abstract A lactating dairy cow was injected intravenously with 2.9 millicuries of uniformly 14C-labeled glucose. The specific activity was determined for plasma glucose and for amino acids of casein during the subsequent 34 hours and these data were used to evaluate glucose as a precursor of amino acids. Glucose carbon was transferred most rapidly and in largest amount to the three carbon amino acids, alanine and serine. Our calculations indicate that 25% of alanine and serine, 10% of aspartic and glutamic acids, and 7% of glycine was derived from plasma glucose. Proposed pathways for the transfer of carbon from glucose to the amino acids are discussed. The amount of glucose carbon transferred to the amino acids via the plasma carbonate pool was evaluated. This indirect pathway, via carbonate, was of minor importance for the non-essential amino acids but was the major pathway for transfer of carbon to the essential amino acids.

Glucose-6-phosphatase activity in various sheep tissues.

Summary Glucose-6-phosphatase activity was estimated in various sheep tissues. It was appreciable in liver and kidney, detectable in intestine and salivary gland, but negligible in brain, muscle, stomach, rumen epithelium and mammary gland. The results suggest the relative importance of these tissues in contributing glucose to the blood in sheep. They indicate particularly the relatively small potential role of sheep intestinal wall as a source of blood glucose.

Glucose metabolism in the lactating dairy cow.

Abstract 1. 1. A lactating Jersey dairy cow was injected intravenously with glucose uniformly labeled with 14 C. The rate at which the injected tracer left the blood stream and the amount and speed with which it appeared in the milk and expired air was measured. 2. 2. Our results indicate that in the cow, the metabolic body glucose pool (62 g or less) was about five times as large as the plasma glucose content (12 g). 3. 3. The turnover time for the body glucose pool was less than one hour and the transfer rate of glucose out of this pool greater than 1 g per minute. 4. 4. The lactating cow derived only about 10% of her exhaled CO 2 from pathways involving the oxidation of body glucose to CO 2 . 5. 5. In the energy metabolism of the lactating cow, glucose is relatively less important than it is in the energy metabolism of dogs and rats.

Relationship between body size and metabolism.

Recently Kleiber has studied the relation in liver slices of oxygen consumption to body weight in rats, rabbits, and sheep. 1 It was shown that the Q02 was inversely proportional to a fractional power of the body weight, so that plotted on a log log grid the data gave a straight line represented by the formula where Q02 is in mm3/mg dry tissue/hour and W is the body weight in kilos. It was concluded that “the factors which determine the metabolic level in vivo seem still to be present in the surviving tissues cut out of the organism.” Subsequent determinations of tissue respiration and observations on the relation of total metabolism to body size justify an additional note on this subject. A recalculation of values from the original individual records of Kleiber gives a coefficient of correlation between log Q02 and log body weight of -0.783 and a coefficient of regression of -0.228 with a standard error of ±0.017. The formula thus becomes. Field has since obtained data on respiration in kidney and brain slices for the rat and rabbit. Although covering only two species, the regression obtained is very similar, the average being -0.199. A value as low as this might be expected to occur by random sampling in data similar to Kleibers about once in 10 times so that the difference can hardly be considered as significant. It is thus apparent that other tissues behave in a manner very similar to liver slices. This strengthens the view previously expressed by Kleiber. On the other hand it is interesting to compare the exponent with that required by the surface area “law”, 0.333.

The tricarboxylic acid cycle as a pathway for transfer of carbon from acetate to amino acids in the intact cow.

Abstract Results are presented on the 14 C distribution revealed by the decarboxylation and complete degradation of amino acids recovered from casein after injecting intact cows with acetate-1- 14 C and acetate-2- 14 C. The labeling pattern in the amino acids provides strong evidence for the theory that the Tricarboxylic Acid Cycle is the pathway for transfer of carbon from acetate to amino acids of casein and to lactose. Our studies with acetate- 14 C support the idea that the Tricarboxylic Acid Cycle functions as a pathway of terminal oxidation and also supplies intermediates for the synthesis of milk constituents.