Question

The complex metabolic pathways in the parasite Trypanosoma brucei were elucidated in part by adding radiolabeled metabolites to cultured parasites. In the parasite, glucose is converted t0 phosphoenolpyruvate (PEP) in the cytosol. PEP then enters an organelle called the glycosome and is converted to oxaloacetate (OAA); OAA is then converted to malate, and malate to fumarate. Fumarate reductase catalyzes the conversion of fumarate to succinate; the succinate is then secreted from the glycosome.

If C1 of glucose is labeled, what carbon(s) in succinate are labeled?

A. C1

B. C2

C. C3

D. C4

E. All of them

Answer 1

When glucose (C6) molecule is phosphorylated, and isomerised followed by another phosphorylation, it forms Fructose-1,6-bisphospahte. The molecule breaks into two components of 3C each: dihydroxyacetone phosphate (DHAP) and glycderaldehyde-3 phosphate (GAP). Carbon 1-3 of glucose form DHAP and 4-6 forms GAP. DHAP then isomerizes to from another molecule of GAP. Carbon 1,2, 3 of DHAP are equivalent to carbon 3, 2, 1 of GAP. Hence carbon 1 of glucose will be considered as carbon 3 of GAP. GAP is then converted to phosphoenol pyruvate (PEP). Hence, if C1 of glucose is radioactively labelled, the C3 of PEP will be radioactively labelled. PEP is converted to oxaloacetate (4C compound), which is reduced to malate (4C). Both will have the C3 as radioactively labelled. Malate is further reduced to form fumarate (4C) and fumarate is reduced to form succinate (4C). Since fumarate and succinate have a symmetrical structure, both will show radioactivity at C3 as well C2 of the structure.

COO- CH*CH* COO- COO- CH2*CH2* COO-

Fumarate Succinate

Hence, options B and C are correct.