Abstract
The proton-coupled folate transporter (PCFT-SLC46A1) is the mechanism by which folates are absorbed across the brush-border membrane of the small intestine. The transporter is also expressed in the choroid plexus and is required for transport of folates into the cerebrospinal fluid. Loss of PCFT function, as occurs in the autosomal recessive disorder "hereditary folate malabsorption" (HFM), results in a syndrome characterized by severe systemic and cerebral folate deficiency. Folate-receptor alpha (FRα) is expressed in the choroid plexus, and loss of function of this protein, as also occurs in an autosomal recessive disorder, results solely in "cerebral folate deficiency" (CFD), the designation for this disorder. This paper reviews the current understanding of the functional and structural properties and regulation of PCFT, an electrogenic proton symporter, and contrasts PCFT properties with those of the reduced folate carrier (RFC), an organic anion antiporter, that is the major route of folate transport to systemic tissues. The clinical characteristics of HFM and its treatment, based upon the thirty-seven known cases with the clinical syndrome, of which thirty have been verified by genotype, are presented. The ways in which PCFT and FRα might interact at the level of the choroid plexus such that each is required for folate transport from blood to cerebrospinal fluid are considered along with the different clinical presentations of HFM and CFD.
| Original language | English (US) |
|---|---|
| Journal | Molecular Aspects of Medicine |
| DOIs | |
| State | Accepted/In press - May 16 2016 |
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Keywords
- 5-Formyltetrahydrofolate (PubChem CID: 143)
- 5-Methyltetrahydrofolate (PubChem CID: 439234)
- Cerebral folate deficiency
- CFD
- Folate receptors
- Folates
- Folic acid
- Folic acid (PubChem CID: 6037)
- FRα
- Hereditary folate malabsorption
- HFM
- Levoleucovorin (PubChem CID: 149436)
- Levomefolic acid (PubChem CID: 444412)
- Methotrexate
- Methotrexate (PubChem CID: 126941)
- PCFT
- Pemetrexed
- Pemetrexed (PubChem CID: 446556)
- Proton-coupled folate transporter
- Reduced folate carrier
- RFC
- SLC19A1
- SLC46A1
ASJC Scopus subject areas
- Medicine(all)
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Clinical Biochemistry
Cite this
The proton-coupled folate transporter (PCFT-SLC46A1) and the syndrome of systemic and cerebral folate deficiency of infancy : Hereditary folate malabsorption. / Zhao, Rongbao; Aluri, Srinivas; Goldman, I. David.
In: Molecular Aspects of Medicine, 16.05.2016.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The proton-coupled folate transporter (PCFT-SLC46A1) and the syndrome of systemic and cerebral folate deficiency of infancy
T2 - Hereditary folate malabsorption
AU - Zhao, Rongbao
AU - Aluri, Srinivas
AU - Goldman, I. David
PY - 2016/5/16
Y1 - 2016/5/16
N2 - The proton-coupled folate transporter (PCFT-SLC46A1) is the mechanism by which folates are absorbed across the brush-border membrane of the small intestine. The transporter is also expressed in the choroid plexus and is required for transport of folates into the cerebrospinal fluid. Loss of PCFT function, as occurs in the autosomal recessive disorder "hereditary folate malabsorption" (HFM), results in a syndrome characterized by severe systemic and cerebral folate deficiency. Folate-receptor alpha (FRα) is expressed in the choroid plexus, and loss of function of this protein, as also occurs in an autosomal recessive disorder, results solely in "cerebral folate deficiency" (CFD), the designation for this disorder. This paper reviews the current understanding of the functional and structural properties and regulation of PCFT, an electrogenic proton symporter, and contrasts PCFT properties with those of the reduced folate carrier (RFC), an organic anion antiporter, that is the major route of folate transport to systemic tissues. The clinical characteristics of HFM and its treatment, based upon the thirty-seven known cases with the clinical syndrome, of which thirty have been verified by genotype, are presented. The ways in which PCFT and FRα might interact at the level of the choroid plexus such that each is required for folate transport from blood to cerebrospinal fluid are considered along with the different clinical presentations of HFM and CFD.
AB - The proton-coupled folate transporter (PCFT-SLC46A1) is the mechanism by which folates are absorbed across the brush-border membrane of the small intestine. The transporter is also expressed in the choroid plexus and is required for transport of folates into the cerebrospinal fluid. Loss of PCFT function, as occurs in the autosomal recessive disorder "hereditary folate malabsorption" (HFM), results in a syndrome characterized by severe systemic and cerebral folate deficiency. Folate-receptor alpha (FRα) is expressed in the choroid plexus, and loss of function of this protein, as also occurs in an autosomal recessive disorder, results solely in "cerebral folate deficiency" (CFD), the designation for this disorder. This paper reviews the current understanding of the functional and structural properties and regulation of PCFT, an electrogenic proton symporter, and contrasts PCFT properties with those of the reduced folate carrier (RFC), an organic anion antiporter, that is the major route of folate transport to systemic tissues. The clinical characteristics of HFM and its treatment, based upon the thirty-seven known cases with the clinical syndrome, of which thirty have been verified by genotype, are presented. The ways in which PCFT and FRα might interact at the level of the choroid plexus such that each is required for folate transport from blood to cerebrospinal fluid are considered along with the different clinical presentations of HFM and CFD.
KW - 5-Formyltetrahydrofolate (PubChem CID: 143)
KW - 5-Methyltetrahydrofolate (PubChem CID: 439234)
KW - Cerebral folate deficiency
KW - CFD
KW - Folate receptors
KW - Folates
KW - Folic acid
KW - Folic acid (PubChem CID: 6037)
KW - FRα
KW - Hereditary folate malabsorption
KW - HFM
KW - Levoleucovorin (PubChem CID: 149436)
KW - Levomefolic acid (PubChem CID: 444412)
KW - Methotrexate
KW - Methotrexate (PubChem CID: 126941)
KW - PCFT
KW - Pemetrexed
KW - Pemetrexed (PubChem CID: 446556)
KW - Proton-coupled folate transporter
KW - Reduced folate carrier
KW - RFC
KW - SLC19A1
KW - SLC46A1
UR - http://www.scopus.com/inward/record.url?scp=84991247318&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84991247318&partnerID=8YFLogxK
U2 - 10.1016/j.mam.2016.09.002
DO - 10.1016/j.mam.2016.09.002
M3 - Article
JO - Molecular Aspects of Medicine
JF - Molecular Aspects of Medicine
SN - 0098-2997
ER -