New study on heme synthesis for red blood cells

A plenary paper featuring students and faculty from the UGA department of biochemistry and molecular biology and the department of microbiology was recently published, highlighted, and given commentary in the journal Blood, the publication of the American Society for Hematology.

The paper, which originated in the lab of professor emeritus Harry Dailey, addresses how erythroid cells acquire sufficient carbon for heme synthesis during erythropoiesis — red blood cell production — according to the commentary by Tracey A. Rouault, M.D., of the National Institutes of Health. 

“These findings overturned long-accepted conventional assumptions about how heme, one essential component of hemoglobin, is synthesized for red blood cells and have implications in understanding the causes and treatments of anemias, particularly during chronic infections,” said Amy Medlock, associate professor at UGA and co-author of the paper along with graduate student Jason Marcero. The work was performed in collaboration with the NIDDK-Sponsored Center for Iron & Hematology Disorders at the University of Utah School of Medicine.

The paper's first author, Joseph Burch (MD/Ph.D. with the university's Biomedical and Health Sciences Institute and the AU/UGA Medical Partnership), completed two years of medical school at the Medical Partnership, then began his Ph.D. program under the mentorship of Dailey. Burch is currently doing his residency in Internal Medicine at Carolinas Medical Center in Charlotte, NC.

According to the paper, it was previously "logical to assume that the carbons of succinyl-CoA were derived from metabolism of glucose through the usual source of succinyl-CoA," but researchers found "glutamine supplied much more carbon to heme than glucose, whereas a succinate compound downstream of succinyl-CoA in the citric acid cycle contributed almost no carbon," Reouault wrote.

"Their discoveries explain how developing erythroid cells can maintain a functional citric acid cycle, even during periods when metabolic activity is heavily skewed toward heme synthesis," Rouault wrote.

Glutamine via α-ketoglutarate dehydrogenase provides succinyl-CoA for heme synthesis during erythropoiesis is available at http://www.bloodjournal.org/content/132/10/987