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Brain Uptake of Selenomethionine Se 75: Title and subTitle BreakII. Reduced Brain Uptake of Selenomethionine Se 75 in Phenylketonuria

William H. Oldendorf, MD; Warden B. Sisson, MD; Arthur Silverstein, PhD
[+] Author Affiliations

Accepted for publication Nov 23, 1970.

Read before the 95th annual meeting of the American Neurological Association, Atlantic City, NJ, June 17, 1970.

Reprint requests to Wadsworth General Hospital, Room C-Gr-37, Wilshire and Sawtelle Boulevards, Los Angeles 90073 (Dr. Oldendorf).


Arch Neurol. 1971;24(6):524-528. doi:10.1001/archneur.1971.00480360058007
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Brain uptake of selenomethionine Se 75 following intravenous injection was studied in nine subjects with phenylketonuria (PKU) and 12 matched mentally retarded controls. Brain content following injection was monitored continuously for 20 minutes using a gamma radiation detector sampling a fixed volume of brain. Uptake was expressed as ratio of head counts per minute divided by dose counts per minute per kilogram of patient. Brain uptake of selenomethionine Se 75 was reduced in the PKU group relative to the control group with a significance of better than 0.001. Reduction of brain uptake of this amino acid analog is compatible with saturation of the blood brain barrier carrier system for selenomethionine Se 75 by the high blood phenylalanine in PKU. Findings derived here by external counting are consistent with previous parallel animal studies in which serum phenylalanine concentrations were elevated by intravenous preloading.

REFERENCES

Oldendorf WH, Sisson WB, Mehta A, et al:  Brain uptake of selenomethionine Se 75: I. Effects of elevated blood levels of methionine and phenylalanine . Arch Neurol 24:423-430, 1971;.
McCaman MW, Robin E:  Fluorimetric method for the determination of phenylalanine in serum . J Lab Clin Med 59:885-890, 1962;.
Awwad HK, Potchen EJ, Adelstein SJ, et al:  Se75-selenomethionine incorporation into human plasma proteins and erythrocytes . Metabolism 15:626-640, 1966;.
Awwad HK, Potchen EJ, Adelstein SJ, et al:  The regional distribution of Se75-selenomethionine in the rat . Metabolism 15:370-378, 1966;.
Awwad HK, Adelstein SJ, Potchen EJ, et al:  The interconversion and reutilization of injected 75Se-selenomethionine in the rat . J Biol Chem 242:492-500, 1967;.
Oldendorf WH, Iisaka Y:  Interference of scalp and skull with external measurements of brain isotope content: I. Isotope content of scalp and skull . J Nucl Med 10:184-187, 1969;.
Knox WE:  Phenylketonuria , in Stanbury JB, Wyngaarden JB, Fredrickson DS (eds): The Metabolic Basis of Inherited Disease , ed 2. New York: McGraw-Hill Book Co, 1966;, pp 258-294.
Yuwiler A, Geller E:  Brain serotonin changes in fed rats: Synthesis storage and degradation . J Neurochem 16:999-1005, 1969;.
McKean CM, Schanberg SM, Giarman NJ:  A mechanism of the indole defect in experimental phenylketonuria . Science 137:605, 1962;.
Schain RJ, Copenhaver JH, Carver MJ:  Inhibition by phenylalanine of the entry of 5-hydroxytryptophan-C14 into cerebrospinal fluid . Proc Soc Exp Biol 118:184-186, 1965;.
Guroff G, Udenfriend S:  Uptake of tyrosine by brain in vivo and in vitro , in Holden JT (ed): Amino Acid Pools . Amsterdam, Elsevier Publishing Co, 1962;, pp 545-553.

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Oldendorf WH, Sisson WB, Mehta A, et al:  Brain uptake of selenomethionine Se 75: I. Effects of elevated blood levels of methionine and phenylalanine . Arch Neurol 24:423-430, 1971;.
McCaman MW, Robin E:  Fluorimetric method for the determination of phenylalanine in serum . J Lab Clin Med 59:885-890, 1962;.
Awwad HK, Potchen EJ, Adelstein SJ, et al:  Se75-selenomethionine incorporation into human plasma proteins and erythrocytes . Metabolism 15:626-640, 1966;.
Awwad HK, Potchen EJ, Adelstein SJ, et al:  The regional distribution of Se75-selenomethionine in the rat . Metabolism 15:370-378, 1966;.
Awwad HK, Adelstein SJ, Potchen EJ, et al:  The interconversion and reutilization of injected 75Se-selenomethionine in the rat . J Biol Chem 242:492-500, 1967;.
Oldendorf WH, Iisaka Y:  Interference of scalp and skull with external measurements of brain isotope content: I. Isotope content of scalp and skull . J Nucl Med 10:184-187, 1969;.
Knox WE:  Phenylketonuria , in Stanbury JB, Wyngaarden JB, Fredrickson DS (eds): The Metabolic Basis of Inherited Disease , ed 2. New York: McGraw-Hill Book Co, 1966;, pp 258-294.
Yuwiler A, Geller E:  Brain serotonin changes in fed rats: Synthesis storage and degradation . J Neurochem 16:999-1005, 1969;.
McKean CM, Schanberg SM, Giarman NJ:  A mechanism of the indole defect in experimental phenylketonuria . Science 137:605, 1962;.
Schain RJ, Copenhaver JH, Carver MJ:  Inhibition by phenylalanine of the entry of 5-hydroxytryptophan-C14 into cerebrospinal fluid . Proc Soc Exp Biol 118:184-186, 1965;.
Guroff G, Udenfriend S:  Uptake of tyrosine by brain in vivo and in vitro , in Holden JT (ed): Amino Acid Pools . Amsterdam, Elsevier Publishing Co, 1962;, pp 545-553.

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