Einstein researchers discover how a key dietary vitamin is absorbed

Their findings, published in the December 1 issue of the journal Cell, solve a longstanding mystery as to how folates in the diet are absorbed and pave the way for a genetic test that can save the lives of infants who lack the ability to absorb folate.

“We can’t live without folate,” says Dr. I. David Goldman, the study’s senior author and director of the Albert Einstein Cancer Center. “Adequate folate in our diet –and our small intestine’s ability to absorb it — are crucial for synthesizing DNA and other important constituents of our bodies. Folate deficiency in the developing embryo can cause developmental nervous-system defects such as spina bifida. After birth, infants with folate deficiency can experience anemia, immune deficiency with severe infections, and neurological defects such as seizures and mental retardation. And in adults, folate deficiency has been associated with an increased risk of certain cancers.”

A water-soluble vitamin such as folate can’t readily penetrate the fatty membrane of cells. It needs a specialized uptake mechanism so it can be absorbed by intestinal cells and ultimately enter the bloodstream. The Einstein researchers identified the membrane protein, dubbed PCFT/HCP1, that transports folate molecules from the small intestine’s acidic milieu into intestinal cells. A study published last year aroused considerable scientific fanfare when it reported that this protein ferried heme linked to iron (which becomes hemoglobin when coupled with the protein globin) into intestinal cells. But the Einstein study shows that folate transport is the primary function of this protein.

The Einstein study also showed that a mutation in the PCFT/HCP1 gene is responsible for hereditary folate malabsorption, a rare but potentially fatal disorder. Infants born with this condition must be treated with high doses of folate to prevent severe anemia and neurological problems that can be fatal or cause irreversible damage. The researchers made the link between mutations in the folate transporter gene and hereditary folate malabsorption by studying a Puerto Rican family in which two children were affected by the condition.

“Families at risk for hereditary folate malabsorption now have a genetic test that can quickly detect this condition before birth or in their newborns,” says Dr. Goldman. “Rapid diagnosis of this disease will insure that these infants will be started on folate supplementation as soon as possible after birth.”