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Folate-Linked Drugs for the Treatment of Cancer and Inflammatory Diseases

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Book cover Water Soluble Vitamins

Part of the book series: Subcellular Biochemistry ((SCBI,volume 56))

Abstract

Folic acid, also known as vitamin B9 (Fig. 9.1), is an essential co-enzyme in one-carbon metabolism pathways, including the biosynthesis of nucleotides (i.e. purines, thymidine) and several amino acids. In general, two functionally different systems mediate the cellular uptake of folate: (1) the reduced folate carrier (RFC, Kd ∼ 10–6 M), an anion transporter that delivers folates across the plasma membrane in a bidirectional fashion, and (2) the folate receptor (FR, Kd ∼ 10–10 M), which internalizes folate through active receptor-mediated endocytosis. The RFC, a membrane-spanning anion transporter, is present in virtually all tissues and is responsible for the majority of folate transport in and out of cells. In contrast, FR expression is largely restricted to malignant cells, activated macrophages, and the proximal tubule cells of the kidneys. Because a variety of important diseases are caused by the former two cell types, interest in exploiting FR for drug targeting applications has rapidly increased. And achievement of this targeting objective, primarily through conjugation of drugs to folic acid is believed to enable (1) enhanced net drug uptake by pathologic cells, and more importantly (2) reduction in drug deposition into non-pathologic cells, thereby mitigating collateral toxicity to normal tissues.

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References

  • Anderson KE, Eliot LA, Stevenson BR, Rogers JA (2001) Formulation and evaluation of a folic acid receptor-targeted oral vancomycin liposomal dosage form. Pharm Res 18:316–322

    Article  PubMed  CAS  Google Scholar 

  • Andersson H, Palm S, Lindegren S, Back T, Jacobsson L, Leser G, Horvath G (2001) Comparison of the therapeutic efficacy of 211At- and 131I-labelled monoclonal antibody MOv18 in nude mice with intraperitoneal growth of human ovarian cancer. Anticancer Res 21:409–412

    PubMed  CAS  Google Scholar 

  • Buist MR, Molthoff CF, Kenemans P, Meijer CJ (1995) Distribution of OV-TL 3 and MOv18 in normal and malignant ovarian tissue. J Clin Pathol 48:631–636

    Article  PubMed  CAS  Google Scholar 

  • Campbell IG, Jones TA, Foulkes WD, Trowsdale J (1991) Folate-binding protein is a marker for ovarian cancer. Cancer Res 51:5329–5338

    PubMed  CAS  Google Scholar 

  • Chatterjee S, Smith ER, Hanada K, Stevens VL, Mayor S (2001) GPI anchoring leads to sphingolipid-dependent retention of endocytosed proteins in the recycling endosomal compartment. Embo J 20:1583–1592

    Article  PubMed  CAS  Google Scholar 

  • Chen WT, Mahmood U, Weissleder R, Tung CH (2005) Arthritis imaging using a near-infrared fluorescence folate-targeted probe. Arthritis Res Ther 7:R310–R317

    Article  PubMed  CAS  Google Scholar 

  • Coney LR, Tomassetti A, Carayannopoulos L, Frasca V, Kamen BA, Colnaghi MI, Zurawski VR Jr (1991) Cloning of a tumor-associated antigen: MOv18 and MOv19 antibodies recognize a folate-binding protein. Cancer Res 51:6125–6132

    PubMed  CAS  Google Scholar 

  • Dreher MR, Liu W, Michelich CR, Dewhirst MW, Yuan F, Chilkoti A (2006) Tumor vascular permeability, accumulation, and penetration of macromolecular drug carriers. J Natl Cancer Inst 98:335–344

    Article  PubMed  CAS  Google Scholar 

  • Evans CO, Young AN, Brown MR, Brat DJ, Parks JS, Neish AS, Oyesiku NM (2001) Novel patterns of gene expression in pituitary adenomas identified by complementary deoxyribonucleic acid microarrays and quantitative reverse transcription-polymerase chain reaction. J Clin Endocrinol Metab 86:3097–3107

    Article  PubMed  CAS  Google Scholar 

  • Friedrichson T, Kurzchalia TV (1998) Microdomains of GPI-anchored proteins in living cells revealed by crosslinking. Nature 394:802–805

    Article  PubMed  CAS  Google Scholar 

  • Garin-Chesa P, Campbell I, Saigo PE, Lewis JL Jr, Old LJ, Rettig WJ (1993) Trophoblast and ovarian cancer antigen LK26. Sensitivity and specificity in immunopathology and molecular identification as a folate-binding protein. Am J Pathol 142:557–567

    PubMed  CAS  Google Scholar 

  • Ghaghada KB, Saul J, Natarajan JV, Bellamkonda RV, Annapragada AV (2005) Folate targeting of drug carriers: a mathematical model. J Control Release 104:113–128

    Article  PubMed  CAS  Google Scholar 

  • Hamann PR, Hinman LM, Hollander I, Beyer CF, Lindh D, Holcomb R, Hallett W, Tsou HR, Upeslacis J, Shochat D, Mountain A, Flowers DA, Bernstein I (2002) Gemtuzumab ozogamicin, a potent and selective anti-CD33 antibody-calicheamicin conjugate for treatment of acute myeloid leukemia. Bioconjug Chem 13:47–58

    Article  PubMed  CAS  Google Scholar 

  • Henne WA, Doorneweerd DD, Hilgenbrink AR, Kularatne SA, Low PS (2006) Synthesis and activity of a folate peptide camptothecin prodrug. Bioorg Med Chem Lett 16:5350–5355

    Article  PubMed  CAS  Google Scholar 

  • Henriksen G, Schoultz BW, Michaelsen TE, Bruland OS, Larsen RH (2004) Sterically stabilized liposomes as a carrier for alpha-emitting radium and actinium radionuclides. Nucl Med Biol 31:441–449

    Article  PubMed  CAS  Google Scholar 

  • Higgs HN, Pollard TD (2001) Regulation of actin filament network formation through ARP2/3 complex: activation by a diverse array of proteins. Annu Rev Biochem 70:649–676

    Article  PubMed  CAS  Google Scholar 

  • Hofland HE, Masson C, Iginla S, Osetinsky I, Reddy JA, Leamon CP, Scherman D, Bessodes M, Wils P (2002) Folate-targeted gene transfer in vivo. Mol Ther 5:739–744

    Article  PubMed  CAS  Google Scholar 

  • Kamen BA, Smith AK (2004) A review of folate receptor alpha cycling and 5-methyltetrahydrofolate accumulation with an emphasis on cell models in vitro. Adv Drug Deliv Rev 56:1085–1097

    Article  PubMed  CAS  Google Scholar 

  • Ke CY, Mathias CJ, Green MA (2004) Folate-receptor-targeted radionuclide imaging agents. Adv Drug Deliv Rev 56:1143–1160

    Article  PubMed  CAS  Google Scholar 

  • Kenworthy AK, Edidin M (1998) Distribution of a glycosylphosphatidylinositol-anchored protein at the apical surface of MDCK cells examined at a resolution of <100 A using imaging fluorescence resonance energy transfer. J Cell Biol 142:69–84

    Article  PubMed  CAS  Google Scholar 

  • Kenworthy AK, Petranova N, Edidin M (2000) High-resolution FRET microscopy of cholera toxin B-subunit and GPI-anchored proteins in cell plasma membranes. Mol Biol Cell 11:1645–1655

    PubMed  CAS  Google Scholar 

  • Ladino CA, Chari RV, Bourret LA, Kedersha NL, Goldmacher VS (1997) Folate-maytansinoids: target-selective drugs of low molecular weight. Int J Cancer 73:859–864

    Article  PubMed  CAS  Google Scholar 

  • Leamon CP, Low PS (1992) Cytotoxicity of momordin-folate conjugates in cultured human cells. J Biol Chem 267:24966–24971

    PubMed  CAS  Google Scholar 

  • Leamon CP, Low PS (1994) Selective targeting of malignant cells with cytotoxin-folate conjugates. J Drug Target 2:101–112

    Article  PubMed  CAS  Google Scholar 

  • Leamon CP, Reddy JA (2004) Folate-targeted chemotherapy. Adv Drug Deliv Rev 56:1127–1141

    Article  PubMed  CAS  Google Scholar 

  • Leamon CP, Pastan I, Low PS (1993) Cytotoxicity of folate-Pseudomonas exotoxin conjugates toward tumor cells. Contribution of translocation domain. J Biol Chem 268:24847–24854

    PubMed  CAS  Google Scholar 

  • Leamon CP, Reddy JA, Vlahov IR, Vetzel M, Parker N, Nicoson JS, Xu LC, Westrick E (2005) Synthesis and biological evaluation of EC72: A new folate-targeted chemotherapeutic. Bioconjug Chem 16:803–811

    Article  PubMed  CAS  Google Scholar 

  • Lu Y, Low PS (2002) Folate targeting of haptens to cancer cell surfaces mediates immunotherapy of syngeneic murine tumors. Cancer Immunol Immunother 51:153–162

    Article  PubMed  CAS  Google Scholar 

  • Lu Y, Low PS (2003) Immunotherapy of folate receptor-expressing tumors: Review of recent advances and future prospects. J Control Release 91:17–29

    Article  PubMed  CAS  Google Scholar 

  • Lu Y, Sega E, Low PS (2005) Folate receptor-targeted immunotherapy: Induction of humoral and cellular immunity against hapten-decorated cancer cells. Int J Cancer 116:710–719

    Article  PubMed  CAS  Google Scholar 

  • Luhrs CA (1991) The role of glycosylation in the biosynthesis and acquisition of ligand-binding activity of the folate-binding protein in cultured KB cells. Blood 77:1171–1180

    PubMed  CAS  Google Scholar 

  • Luhrs CA, Pitiranggon P, da Costa M, Rothenberg SP, Slomiany BL, Brink L, Tous GI, Stein S (1987) Purified membrane and soluble folate binding proteins from cultured KB cells have similar amino acid compositions and molecular weights but differ in fatty acid acylation. Proc Natl Acad Sci USA 84:6546–6549

    Article  PubMed  CAS  Google Scholar 

  • Mayor S, Sabharanjak S, Maxfield FR (1998) Cholesterol-dependent retention of GPI-anchored proteins in endosomes. Embo J 17:4626–4638

    Article  PubMed  CAS  Google Scholar 

  • Maziarz KM, Monaco HL, Shen F, Ratnam M (1999) Complete mapping of divergent amino acids responsible for differential ligand binding of folate receptors alpha and beta. J Biol Chem 274:11086–11091

    Article  PubMed  CAS  Google Scholar 

  • Melani C, Figini M, Nicosia D, Luison E, Ramakrishna V, Casorati G, Parmiani G, Eshhar Z, Canevari S, Colombo MP (1998) Targeting of interleukin 2 to human ovarian carcinoma by fusion with a single-chain Fv of antifolate receptor antibody. Cancer Res 58:4146–4154

    PubMed  CAS  Google Scholar 

  • Mezzanzanica D, Canevari S, Colnaghi MI (1991) Retargeting of human lymphocytes against human ovarian carcinoma cells by bispecific antibodies: From laboratory to clinic. Int J Clin Lab Res 21:159–164

    Article  PubMed  CAS  Google Scholar 

  • Nakashima-Matsushita N, Homma T, Yu S, Matsuda T, Sunahara N, Nakamura T, Tsukano M, Ratnam M, Matsuyama T (1999) Selective expression of folate receptor beta and its possible role in methotrexate transport in synovial macrophages from patients with rheumatoid arthritis. Arthritis Rheum 42:1609–1616

    Article  PubMed  CAS  Google Scholar 

  • Ni S, Stephenson SM, Lee RJ (2002) Folate receptor targeted delivery of liposomal daunorubicin into tumor cells. Anticancer Res 22:2131–2135

    PubMed  CAS  Google Scholar 

  • Orr RB, Kreisler AR, Kamen BA (1995) Similarity of folate receptor expression in UMSCC 38 cells to squamous cell carcinoma differentiation markers. J Natl Cancer Inst 87:299–303

    Article  PubMed  CAS  Google Scholar 

  • Pan XQ, Lee RJ (2005) In vivo antitumor activity of folate receptor-targeted liposomal daunorubicin in a murine leukemia model. Anticancer Res 25:343–346

    PubMed  CAS  Google Scholar 

  • Pan XQ, Zheng X, Shi G, Wang H, Ratnam M, Lee RJ (2002) Strategy for the treatment of acute myelogenous leukemia based on folate receptor beta-targeted liposomal doxorubicin combined with receptor induction using all-trans retinoic acid. Blood 100:594–602

    Article  PubMed  CAS  Google Scholar 

  • Parker N, Turk MJ, Westrick E, Lewis JD, Low PS, Leamon CP (2005) Folate receptor expression in carcinomas and normal tissues determined by a quantitative radioligand binding assay. Anal Biochem 338:284–293

    Article  PubMed  CAS  Google Scholar 

  • Parton RG, Richards AA (2003) Lipid rafts and caveolae as portals for endocytosis: New insights and common mechanisms. Traffic 4:724–738

    Article  PubMed  CAS  Google Scholar 

  • Paulos CM, Turk MJ, Breur GJ, Low PS (2004a) Folate receptor-mediated targeting of therapeutic and imaging agents to activated macrophages in rheumatoid arthritis. Adv Drug Deliv Rev 56:1205–1217

    Article  PubMed  CAS  Google Scholar 

  • Paulos CM, Reddy JA, Leamon CP, Turk MJ, Low PS (2004b) Ligand binding and kinetics of folate receptor recycling in vivo: Impact on receptor-mediated drug delivery. Mol Pharmacol 66:1406–1414

    Article  PubMed  CAS  Google Scholar 

  • Paulos CM, Varghese B, Widmer WR, Breur GJ, Vlashi E, Low PS (2006) Folate-targeted immunotherapy effectively treats established adjuvant and collagen-induced arthritis. Arthritis Res Ther 8:R77

    Article  PubMed  Google Scholar 

  • Reddy JA, Dean D, Kennedy MD, Low PS (1999a) Optimization of folate-conjugated liposomal vectors for folate receptor-mediated gene therapy. J Pharm Sci 88:1112–1118

    Article  PubMed  CAS  Google Scholar 

  • Reddy JA, Haneline LS, Srour EF, Antony AC, Clapp DW, Low PS (1999b) Expression and functional characterization of the beta-isoform of the folate receptor on CD34(+) cells. Blood 93:3940–3948

    PubMed  CAS  Google Scholar 

  • Reddy JA, Abburi C, Hofland H, Howard SJ, Vlahov I, Wils P, Leamon CP (2002) Folate-targeted, cationic liposome-mediated gene transfer into disseminated peritoneal tumors. Gene Ther 9:1542–1550

    Article  PubMed  CAS  Google Scholar 

  • Reddy JA, Low PS (2000) Enhanced folate receptor mediated gene therapy using a novel pH-sensitive lipid formulation. J Control Release 64:27–37

    Article  PubMed  CAS  Google Scholar 

  • Reddy JA, Westrick E, Vlahov I, Howard SJ, Santhapuram HK, Leamon CP (2006) Folate receptor specific anti-tumor activity of folate-mitomycin conjugates. Cancer Chemother Pharmacol 58:229–236

    Article  PubMed  CAS  Google Scholar 

  • Rijnboutt S, Jansen G, Posthuma G, Hynes JB, Schornagel JH, Strous GJ (1996) Endocytosis of GPI-linked membrane folate receptor-alpha. J Cell Biol 132:35–47

    Article  PubMed  CAS  Google Scholar 

  • Roberts SJ, Petropavlovskaja M, Chung KN, Knight CB, Elwood PC (1998) Role of individual N-linked glycosylation sites in the function and intracellular transport of the human alpha folate receptor. Arch Biochem Biophys 351:227–235

    Article  PubMed  CAS  Google Scholar 

  • Ross JF, Chaudhuri PK, Ratnam M (1994) Differential regulation of folate receptor isoforms in normal and malignant tissues in vivo and in established cell lines. Physiologic and clinical implications. Cancer 73:2432–2443

    Article  PubMed  CAS  Google Scholar 

  • Ross JF, Wang H, Behm FG, Mathew P, Wu M, Booth R, Ratnam M (1999) Folate receptor type beta is a neutrophilic lineage marker and is differentially expressed in myeloid leukemia. Cancer 85:348–357

    Article  PubMed  CAS  Google Scholar 

  • Sabharanjak S, Mayor S (2004) Folate receptor endocytosis and trafficking. Adv Drug Deliv Rev 56:1099–1109

    Article  PubMed  CAS  Google Scholar 

  • Sabharanjak S, Sharma P, Parton RG, Mayor S (2002) GPI-anchored proteins are delivered to recycling endosomes via a distinct cdc42-regulated, clathrin-independent pinocytic pathway. Dev Cell 2:411–423

    Article  PubMed  CAS  Google Scholar 

  • Sandoval RM, Kennedy MD, Low PS, Molitoris BA (2004) Uptake and trafficking of fluorescent conjugates of folic acid in intact kidney determined using intravital two-photon microscopy. Am J Physiol Cell Physiol 287:C517–C526

    Article  PubMed  CAS  Google Scholar 

  • Shen F, Ross JF, Wang X, Ratnam M (1994) Identification of a novel folate receptor, a truncated receptor, and receptor type beta in hematopoietic cells: cDNA cloning, expression, immunoreactivity, and tissue specificity. Biochemistry 33:1209–1215

    Article  PubMed  CAS  Google Scholar 

  • Shen F, Wang H, Zheng X, Ratnam M (1997b) Expression levels of functional folate receptors alpha and beta are related to the number of N-glycosylated sites. Biochem J 327(Pt 3):759–764

    PubMed  CAS  Google Scholar 

  • Shen F, Zheng X, Wang J, Ratnam M (1997a) Identification of amino acid residues that determine the differential ligand specificities of folate receptors alpha and beta. Biochemistry 36:6157–6163

    Article  PubMed  CAS  Google Scholar 

  • Stein R, Goldenberg DM, Mattes MJ (1991) Normal tissue reactivity of four anti-tumor monoclonal antibodies of clinical interest. Int J Cancer 47:163–169

    Article  PubMed  CAS  Google Scholar 

  • Stephenson SM, Yang W, Stevens PJ, Tjarks W, Barth RF, Lee RJ (2003) Folate receptor-targeted liposomes as possible delivery vehicles for boron neutron capture therapy. Anticancer Res 23:3341–3345

    PubMed  CAS  Google Scholar 

  • Stevens PJ, Sekido M, Lee RJ (2004) A folate receptor-targeted lipid nanoparticle formulation for a lipophilic paclitaxel prodrug. Pharm Res 21:2153–2157

    Article  PubMed  CAS  Google Scholar 

  • Sudimack JJ, Adams D, Rotaru J, Shukla S, Yan J, Sekido M, Barth RF, Tjarks W, Lee RJ (2002) Folate receptor-mediated liposomal delivery of a lipophilic boron agent to tumor cells in vitro for neutron capture therapy. Pharm Res 19:1502–1508

    Article  PubMed  CAS  Google Scholar 

  • Takenawa T, Miki H (2001) WASP and WAVE family proteins: Key molecules for rapid rearrangement of cortical actin filaments and cell movement. J Cell Sci 114:1801–1809

    PubMed  CAS  Google Scholar 

  • Toffoli G, Cernigoi C, Russo A, Gallo A, Bagnoli M, Boiocchi M (1997) Overexpression of folate binding protein in ovarian cancers. Int J Cancer 74:193–198

    Article  PubMed  CAS  Google Scholar 

  • Turek JJ, Leamon CP, Low PS (1993) Endocytosis of folate-protein conjugates: Ultrastructural localization in KB cells. J Cell Sci 106(Pt 1):423–430

    PubMed  CAS  Google Scholar 

  • Turk MJ, Breur GJ, Widmer WR, Paulos CM, Xu LC, Grote LA, Low PS (2002) Folate-targeted imaging of activated macrophages in rats with adjuvant-induced arthritis. Arthritis Rheum 46:1947–1955

    Article  PubMed  Google Scholar 

  • van Meer G, Sprong H (2004) Membrane lipids and vesicular traffic. Curr Opin Cell Biol 16:373–378

    Article  PubMed  Google Scholar 

  • van Zanten-Przybysz I, Molthoff CF, Roos JC, Plaizier MA, Visser GW, Pijpers R, Kenemans P, Verheijen RH (2000) Radioimmunotherapy with intravenously administered 131I-labeled chimeric monoclonal antibody MOv18 in patients with ovarian cancer. J Nucl Med 41:1168–1176

    PubMed  Google Scholar 

  • van Zanten-Przybysz I, Molthoff C, Gebbinck JK, von Mensdorff-Pouilly S, Verstraeten R, Kenemans P, Verheijen R (2002) Cellular and humoral responses after multiple injections of unconjugated chimeric monoclonal antibody MOv18 in ovarian cancer patients: A pilot study. J Cancer Res Clin Oncol 128:484–492

    Article  PubMed  Google Scholar 

  • Veggian R, Fasolato S, Menard S, Minucci D, Pizzetti P, Regazzoni M, Tagliabue E, Colnaghi MI (1989) Immunohistochemical reactivity of a monoclonal antibody prepared against human ovarian carcinoma on normal and pathological female genital tissues. Tumori 75:510–513

    PubMed  CAS  Google Scholar 

  • Wang X, Shen F, Freisheim JH, Gentry LE, Ratnam M (1992) Differential stereospecificities and affinities of folate receptor isoforms for folate compounds and antifolates. Biochem Pharmacol 44:1898–1901

    Article  PubMed  CAS  Google Scholar 

  • Weitman SD, Weinberg AG, Coney LR, Zurawski VR, Jennings DS, Kamen BA (1992a) Cellular localization of the folate receptor: Potential role in drug toxicity and folate homeostasis. Cancer Res 52:6708–6711

    PubMed  CAS  Google Scholar 

  • Weitman SD, Lark RH, Coney LR, Fort DW, Frasca V, Zurawski VR Jr, Kamen BA (1992b) Distribution of the folate receptor GP38 in normal and malignant cell lines and tissues. Cancer Res 52:3396–3401

    PubMed  CAS  Google Scholar 

  • Wu M, Gunning W, Ratnam M (1999) Expression of folate receptor type alpha in relation to cell type, malignancy, and differentiation in ovary, uterus, and cervix. Cancer Epidemiol Biomarkers Prev 8:775–782

    PubMed  CAS  Google Scholar 

  • Xia W, Hilgenbrink AR, Matteson EL, Lockwood MB, Cheng JX, Low PS (2009) A functional folate receptor is induced during macrophage activation and can be used to target drugs to activated macrophages. Blood Jan 8;113(2):438–446. Epub 2008 Oct 24

    CAS  Google Scholar 

  • Yan W, Shen F, Dillon B, Ratnam M (1998) The hydrophobic domains in the carboxyl-terminal signal for GPI modification and in the amino-terminal leader peptide have similar structural requirements. J Mol Biol 275:25–33

    Article  PubMed  CAS  Google Scholar 

  • Zheng DB, Lim HM, Pene JJ, White HB 3rd (1988) Chicken riboflavin-binding protein. cDNA sequence and homology with milk folate-binding protein. J Biol Chem 263:11126–11129

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. St. Jude Children’s Research Hospital, Memphis, TN, USA

    Jun Yang

  2. Purdue University, West Lafayette, IN, USA

    Jun Yang, Erina Vlashi & Philip Low

  3. University of California, Los Angeles, CA, USA

    Erina Vlashi

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  1. Jun Yang
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  2. Erina Vlashi
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  3. Philip Low
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Correspondence to Philip Low .

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  1. Imperial College of Science, Technology and Medicine, Royal Brompton & Harefield NHS Foundatio, Sydney Street, London, SW3 6NP, United Kingdom

    Olaf Stanger

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Yang, J., Vlashi, E., Low, P. (2012). Folate-Linked Drugs for the Treatment of Cancer and Inflammatory Diseases. In: Stanger, O. (eds) Water Soluble Vitamins. Subcellular Biochemistry, vol 56. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2199-9_9

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