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Biochemistry

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Glycolysis and the PPP: Tracing Radiolabeled Glucose

BIOCHM-YIH0ED

There is considerable interest in understanding the regulation of glucose metabolism through the interconnected glycolytic and pentose phosphate pathways (PPP) (see image below) to possibly reveal potential drug targeting sites.

Several studies suggest greater flux through the PPP in cancer cells yielding NADPH which protects against oxidative stress, as well as intermediates for nucleotide biosynthesis for the rapidly dividing cells.

One way to study the flux of glucose between the two pathways is to incubate cells with differently labeled $_{ }^{ 13 }{ C }$-glucose and follow its metabolic fate using $_{ }^{ 13 }{ C }$ NMR.

Use the simplified glycolytic and PPP template shown below as a guide (note that not all cofactors, small molecules, etc., are shown) to determine which of the following statements correctly describes the major fate of the label in glucose if metabolized to lactate preferentially via only glycolysis vs. first by the PPP and then glycolysis, as indicated.

Jiang, Peng, Wenjing Du, and Mian Wu. “Regulation of the Pentose Phosphate Pathway in Cancer.” Protein & Cell 5.8 (2014): 592–602. PMC. Web. 2 Apr. 2016.

A

Cells labeled with ${ 1- }_{ }^{ 13 }{ C }{ -glucose }$ would produce lactate singly labeled in C1 if metabolized first by the PPP and then glycolysis.

B

Cells labeled with ${ 6- }_{ }^{ 13 }{ C }{ -glucose }$ would produce lactate singly labeled in C3 if metabolized by glycolysis, whereas no label would be found in lactate if metabolized first by the PPP and then glycolysis.

C

Cells labeled with ${ 1,2- }_{ }^{ 13 }{ C }_{ 2 }{ -glucose }$ would produce lactate singly labeled in C3 if metabolized first by the PPP and then glycolysis.

D

Cells labeled with ${ 1,2- }_{ }^{ 13 }{ C }_{ 2 }{ -glucose }$ would produce lactate doubly labeled in C2 and C3 if metabolized first by the PPP and then glycolysis.

E

Cells labeled with ${ 1,2- }_{ }^{ 13 }{ C }_{ 2 }{ -glucose }$ would produce lactate doubly labeled in C1 and C2 if metabolized by glycolysis.