Substrate cycling between pyruvate and oxaloacetate in awake normal and 3,3'-5-triiodo-L-thyronine-treated rats.
Substrate cycling between pyruvate and oxaloacetate was assessed in awake 24-h fasted normal and triiodothyronine (T3)-treated rats. After a 20- or 60-min infusion of [3-13C]alanine (99% enriched, 12 mg/min) the 13C enrichments of liver glucose and alanine carbons were analyzed by 13C and 1H nuclear magnetic resonance spectroscopy and gas chromatography-mass spectrometry. Substrate cycling from phosphoenolpyruvate to pyruvate [via pyruvate kinase (PK)] and from oxaloacetate to pyruvate [via malic enzyme (ME)] relative to the pyruvate carboxylase (PC) flux [i.e., (PK+ME)/PC] was assessed by the ratio of the 13C enrichment of C-2 alanine relative to that in C-5 glucose. In the normal rats (PK+ME)/PC was 0.26 +/- 0.07 (n = 7, t = 20 min) and 0.37 +/- 0.08 (n = 4, t = 60 min). In the T3-treated rats the (PK+ME)/PC increased four- to fivefold to 1.03 +/- 0.19 (n = 8, t = 20 min) and to 1.83 +/- 0.19 (n = 3, t = 60 min) (P < 0.05 vs. normal rats). The liver enzyme activity of PK did not change with T3 treatment (normal 14.22 +/- 5.25 U/g liver vs. T3 treated 13.40 +/- 1.10 U/g liver), whereas both the enzyme activity ratio of PK (normal 0.47 +/- 0.15 vs. T3 treated 0.77 +/- 0.03, P < 0.05) and the activity of ME (normal 0.89 +/- 0.30 U/g liver vs. T3 treated 4.25 +/- 0.60 U/g liver, P < 0.05) increased with T3 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Petersen
K F
KF
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8020.
Cline
G W
GW
Blair
J B
JB
Shulman
G I
GI
D000409:Alanine / Q000378:metabolism; D000818:Animals; D005947:Glucose / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008291:Malate Dehydrogenase / Q000378:metabolism; D008297:Male; D010071:Oxaloacetates / Q000378:metabolism*; D011766:Pyruvate Carboxylase / Q000378:metabolism; D011770:Pyruvate Kinase / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism*; D019289:Pyruvic Acid; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D015219:Substrate Cycling / Q000187:drug effects; D013997:Time Factors; D014284:Triiodothyronine / Q000494:pharmacology*
D010071:Oxaloacetates; D011773:Pyruvates; D014284:Triiodothyronine; D019289:Pyruvic Acid; D008291:Malate Dehydrogenase; C030574:malate dehydrogenase (decarboxylating); D011770:Pyruvate Kinase; D011766:Pyruvate Carboxylase; D005947:Glucose; D000409:Alanine