VOL. 4 (1950) METABOLIC RATE OF THE LIVER 32? 



added to the blood after the oxygen uptake has reached its constant low level only 

 a very slight increase in the oxygen uptake or no increase at all is observed. Consequently 

 the possibihty that the lactic acid concentration in the blood is responsible for the 

 changes in oxygen consumption observed in these experiments can be definitely ruled out. 



If lactic acid is added to the blood after the oxygen uptake of an isolated liver has 

 been allowed to drop off the rate of disappearance of lactic acid amounts to only one 

 fourth to one third of the rate observed in a liver connected with a donor. Thus not only 

 the rate of oxygen consumption but also the rate of a reaction such as conversion of 

 lactic acid to glucose or glycogen is influenced by the hypothetical substance present in 

 fresh blood. The statement appears justified that this substance influences the "meta- 

 bolic rate" of the liver. 



The nature of the substance influencing the metabolic rate of the liver has not been 

 elucidated; accordingly, this paper can be considered only as a preliminary note. A series 

 of substances however can be ruled out since they have no effect on the rate of oxygen 

 uptake in the liver when added to the blood about one hour after the start of the per- 

 fusion. Some of these substances have been added to the blood in a single dose, others 

 have been added continuously at a rate giving concentrations in the blood comparable 

 with the normal concentrations. Without going into details a few of the substances 

 tested so far are listed (Table II). 



TABLE II 



"Kochsaft" of muscle Choline 



Fresh muscle extract Methionine 



ATP Tyrosine 



Creatine Tryptophan 



Cytochrom C Arginine 



Glutathione Threonine 



Citric acid Ascorbic acid 



Oxalo-acetic acid AdrenaUne 



Fu marie acid nor- Adrenaline 



Succinic acid Desoxycorticosterone glycoside (Ciba) 



Pyruvic acid "Corsunal"* 



Lactic acid Insulin 



Acetic acid Fresh crude extract of anterior pituitary 



* Extract of ox-adrenals prepared by Nordisk Insulin Laboratory according to Grollman 



AND FiROR 



Among the substances listed in Table II only adrenaline and nor-adrenaline had 

 a definite but quite transitory effect of increasing oxygen uptake. This effect, however, 

 could not be maintained by continuous addition of the substances. 



It must be mentioned that pyruvic acid and the aminoacids glycine and alanine in 

 large doses (300 mg) have a marked effect on the oxygen uptake in the isolated liverV 

 As continuous addition of pyruvic acid at a rate of 2 mg per minute (blood flow 50 to 

 60 ml/min) has no effect on the oxygen uptake and as the amino acid content in blood 

 perfused through a liver does not decrease as does the oxygen uptake during the first 

 period of the experiment it appears that pyruvic acid and amino acids can safely be 

 ruled out as factors responsible for the changes in oxygen uptake in the Hver observed 

 in these experiments. 



The problem to which attention is directed in the present paper undoubtedly is 



References p. 32 g. 



