1. Withdrawal of food from lactating rats produced a rapid and dramatic decrease in the uptake of
glucose by the mammary gland and an inhibition of the rate of
fatty acid synthesis that could not be explained alone by decreased substrate supply to the tissue. 2. Within the first 6 hr
starvation,
fatty acid synthesis and
pyruvate dehydrogenase activity were inhibited by 87 and 80%, respectively, but
acetyl-CoA carboxylase activity did not change significantly. 3. Between 6 and 24 hr
starvation, total and expressed activities of
acetyl-CoA carboxylase decreased by 62 and 55%, respectively. 4. The ratio of
fructose-6-
phosphate/
fructose-1,6-bisphosphate concentration in mammary tissue increased 9-fold during the first 6 hr
starvation, indicating an inhibition of
6-phosphofructo-1-kinase. However, the major inhibition of this
enzyme occurred between 6 and 24 hr
starvation when this metabolite ratio increased a further 160-fold in parallel with increased tissue
citrate concentration. 5. The increase in
citrate concentration between 6 and 24 hr
starvation correlated with
acetyl-CoA carboxylase inactivation and
ketone body accumulation in the mammary gland. 6. This study confirms the asynchronous control of three important regulatory steps in the pathway of
glucose utilization and
fatty acid synthesis in the lactating rat mammary gland.