Esenmo E, Chandramouli V, Schumann W C, Kumaran K, Wahren J, Landau B R
Department of Clinical Physiology, Karolinska Hospital, Stockholm, Sweden.
Am J Physiol. 1992 Jul;263(1 Pt 1):E36-41. doi: 10.1152/ajpendo.1992.263.1.E36.
Estimating the rate of hepatic gluconeogenesis in vivo from the incorporation of 14C from 14CO2 into glucose requires determination of the rates in liver of equilibration of oxaloacetate with fumarate, conversion of oxaloacetate to phosphoenolpyruvate (PEP), and conversion of PEP to pyruvate, all relative to the rate of tricarboxylic acid cycle flux. With the use of a model of mitochondrial metabolism and gluconeogenesis, expressions are derived relating specific activity of carboxyl of PEP from 14CO2 to those rates and specific activity of mitochondrial CO2. If those rates and specific activity of mitochondrial CO2 are known, specific activity of PEP, calculated using the expressions, should, on a mole basis, be one-half the specific activity of the glucose formed. At steady state, in the 60-h fasted individual, where glucose formation is solely by gluconeogenesis, twice estimated specific activity of PEP should then approximate that of blood glucose. Estimates of relative rates in 60-h fasted humans, previously made from distribution of 14C in glutamate from phenylacetylglutamine excreted when [3-14C]lactate and phenylacetate were given, were applied to the expressions. Specific activity of mitochondrial CO2 was equated to that of CO2 expired by 60-h fasted subjects given NaH14CO3 and alpha-[1-14C]ketoisocaproate. Predicted specific activities approximated actual specific activities of blood glucose when NaH14CO3 was administered. alpha-[1-14C]ketoisocaproate administrations gave underestimates. This is attributable to differences between specific activities of hepatic mitochondrial CO2 and expired CO2, which is evidenced by higher incorporations of 14C in glucose than in expired CO2 from alpha-[1-14C]ketoisocaproate than from NaH14CO3.(ABSTRACT TRUNCATED AT 250 WORDS)
通过14CO2中的14C掺入葡萄糖来体内估计肝糖异生速率，需要确定草酰乙酸与富马酸平衡、草酰乙酸转化为磷酸烯醇式丙酮酸（PEP）以及PEP转化为丙酮酸在肝脏中的速率，所有这些都相对于三羧酸循环通量的速率。利用线粒体代谢和糖异生模型，推导了将来自14CO2的PEP羧基的比活与这些速率以及线粒体CO2的比活相关联的表达式。如果已知这些速率和线粒体CO2的比活，使用这些表达式计算出的PEP比活，按摩尔计算，应该是所形成葡萄糖比活的一半。在稳态下，对于禁食60小时的个体，此时葡萄糖仅通过糖异生来形成，那么估计的PEP比活的两倍应该接近血糖的比活。先前根据给予[3-14C]乳酸和苯乙酸时排泄的苯乙酰谷氨酰胺中14C在谷氨酸中的分布对禁食60小时的人体中的相对速率进行的估计，被应用于这些表达式。线粒体CO2的比活等同于给予NaH14CO3和α-[1-14C]酮异己酸的禁食60小时受试者呼出的CO2的比活。当给予NaH14CO3时，预测的比活接近血糖的实际比活。给予α-[1-14C]酮异己酸会导致低估。这归因于肝线粒体CO2和呼出CO2的比活之间的差异，这由α-[1-14C]酮异己酸中14C在葡萄糖中的掺入高于在呼出CO2中的掺入所证明，而NaH14CO3的情况则相反。（摘要截断于250字）
