Search

Blood-to-brain amino acid transport consists of at least two components: 1. a fast rate or early process, commonly measured by the intra-carotid bolus injection method and attributed to transport across the capillary endothelium and entry into the astrocytes, and, 2. a slow rate or later component measured over 2 to 15 minutes probably associated with exit from the astrocytes and entry into the neurons. Incorporation into brain protein is temporally related to the second process. In the present study the slow and fast rate transport components and the incorporation into brain protein of tyrosine (Tyr) and Valine (Val) was measured in young adult and aged male C57BL/6 mice. The results indicate that the fast rate transport component is unaffected by age while the rates of the slow process and protein turnover show an exponential decline most marked between 3 and 8 months of age. Changes in the relative incorporation of Tyr and Val suggest that brain protein metabolism is altered qualitatively as well as quantitatively in aging, in these animals.

Two inhibitors of the gamma-glutamyl cycle, methionine sulfoximine (MSO) and 2-imidazolidone-4-carboxylic acid (ICA) were administered to C57LB/6J mice. Both agents resulted in a reduced rate of transport of tyrosine from blood to brain and a decreased rate of incorporation of tyrosine from plasma into brain protein. MSO administration also diminished to concentrations of brain tyrosine, dopamine, and norepinephrine. MSO decreased the transport rate of valine by brain as well as the rate of its incorporation into protein when expressed in relation to the plasma specific activity. The results demonstrate a significant role for the gamma-glutamyl cycle in the transport of large neutral amino acids from blood to brain.

In vivo inhibition of uptake 14C-L-valine by brain following subcutaneous administration of either of two gamma-glutamyl cycle enzyme inhibitors, 2-imidazolidone-4-carboxylic acid (ICA), or, L-methionine-S-sulfoximine (MSO) is documented in C57BL/6J mice. Dose related decrease in exploratory activity, impairment of memory for foot shock, and reduced operant responding for food reinforcement parallels the time course for interference with uptake of a large neutral amino acid by these two compounds previously shown to inhibit different enzymes in the gamma-glutamyl cycle subserving active amino acid transport.

Rates of tyrosine and lysine transport and incorporation into protein were measured in control and undernourished weanling rats. Undernutrition was induced by feeding lactating dams a low protein diet (12 percent casein) from birth to day 21. At weaning, body and brain weights of undernourished rats were 50 percent and 88 percent, respectively, of control values. Lysine and tyrosine transport rates into skeletal muscle were reduced by over 75 percent, more than twice the reduction seen in brain. Rates of amino acid incorporation into muscle protein were reduced by approximately 50 percent; the change in rate of incorporation into brain protein was not statistically significant. These data indicate that, in spite of marked retardation of amino acid transport into brain, the brain seems fully capable of maintaining normal rates of protein synthesis.