Gluconeogenesis in Birds

It is a characteristic of all avian species that they maintain a plasma glucose concentration between 9 and 15 mM under all physiological circumstances. Even starvation for up to 9 days failed to lower the blood sugar concentration of chickens (Hazelwood & Lorenz, 1959). This concentration is much greater than that found in most mammals and yet, by contrast, the glycogen stores of avian liver are rather lower than those of most mammals. Hence birds require an active gluconeogenic pathway to maintain their plasma glucose concentration during food deprivation and under various forms of stress. The fertile chicken egg contains relatively little carbohydrate, but after 18 days incubation the liver contains 20mg of glycogen/g wet weight and this falls below lOmg/g weight at hatching (Gill, 1938; R. S. Campbell & D. R. Langslow, unpublished observations). Most of this glycogen must be derived from the endogenous protein stores of the egg and during the final week of incubation the chick embryo has an extremely active gluconeogenic pathway. Hence, in addition to the usual role of gluconeogenesis in starvation and stress, birds also depend on gluconeogenesis during their embryonic existence. The major pathways of glucose metabolism in birds are similar to those of other animals, except that the pentose phosphate pathway is rather inactive, especially in liver (O’Hea & Leveille, 1968; Duncan, 1968), and glucokinase is absent from avian liver (Ureta et a[., 1973; O’Neill & Langslow, 1976, 1978~). The rates of glucose turnover and recycling are substantially higher in chickens than in rats (Brady et al., 1977). Some of the enzymes concerned with glucose metabolism show some important differences between birds and mammals. Both phosphoenolpyruvate carboxykinase (EC 4.1.1.32) and alanine aminotransferase (EC 2.6.1.2) are almost entirely mitochondria1 in chickens and other birds while less than 10% of their activity is mitochondrial in rat liver (Utter, 1959; Sarker, 1977). The absence of glucokinase poses a problem for the regulation of glucose uptake by avian liver. Glucose uptake is regulated by substrate cycling between glucose and glucose 6-phosphate. Both the activity and K, of glucose 6-phosphatase (EC 3.1.3.9) are altered under different conditions. Starvation, for example, increases the activity of the enzyme and lowers the K , (O’Neill & Langslow, 1976, 1978a,b). Furthermore, the rapid rate of loss of 3H from [3H]glucose suggests that this cycle occurs twice as fast in chickens as in rats (Brady et al., 1977). Fructose 1,dbisphosphatase (EC 3.1.3.11) also differs from the typical mammalian enzyme. Its K, for fructose 1,6-bisphosphate is only l O p ~ and the enzyme is inhibited by 70% by 200p~-fructose 1,6-bisphosphate (R. S. Campbell & D. R. Langslow, unpublished observations).