Covalent modification of the
pyruvate dehydrogenase complex provides an important regulatory mechanism for controlling the disposal of
glucose and other compounds metabolized to
pyruvate. Regulation of the complex by this mechanism is achieved in part by tissue-specific expression of the genes encoding
isoenzymes of
pyruvate dehydrogenase kinase (PDK).
Starvation is known from our previous work to increase PDK activity of heart and skeletal muscle by increasing the amount of PDK
isoenzyme 4 (PDK4) present in these tissues. This study demonstrates that increased expression of both PDK4 and PDK2 occurs in rat liver, kidney, and lactating mammary gland in response to
starvation. PDK4 and PDK2 message levels were also increased by
starvation in the two tissues examined (liver and kidney), suggesting enhancement of gene transcription. Changes in PDK2 message and
protein were of similar magnitude, but changes in PDK4 message were greater than those in PDK4
protein, suggesting regulation at the level of translation. In contrast to these tissues,
starvation had little or no effect on PDK2 and PDK4
protein in brain, white adipose tissue, and brown adipose tissue. Nevertheless, PDK4 message levels were significantly increased in brain and white adipose tissue by
starvation. The findings of this study indicate that increased expression of PDK
isoenzymes is an important mechanism for bringing about inactivation of the
pyruvate dehydrogenase complex during
starvation in many but not all tissues of the body. The absence of this mechanism preserves the capacity of neuronal tissue to utilize
glucose for energy during
starvation.