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European Journal of Nutrition

Erschienen in:

14.08.2020 | Review

Choline in cystic fibrosis: relations to pancreas insufficiency, enterohepatic cycle, PEMT and intestinal microbiota

verfasst von: Wolfgang Bernhard

Erschienen in: European Journal of Nutrition | Ausgabe 4/2021

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Abstract

Background

Cystic Fibrosis (CF) is an autosomal recessive disorder with life-threatening organ manifestations. 87% of CF patients develop exocrine pancreas insufficiency, frequently starting in utero and requiring lifelong pancreatic enzyme substitution. 99% develop progressive lung disease, and 20–60% CF-related liver disease, from mild steatosis to cirrhosis. Characteristically, pancreas, liver and lung are linked by choline metabolism, a critical nutrient in CF. Choline is a tightly regulated tissue component in the form of phosphatidylcholine (Ptd’Cho) and sphingomyelin (SPH) in all membranes and many secretions, particularly of liver (bile, lipoproteins) and lung (surfactant, lipoproteins). Via its downstream metabolites, betaine, dimethylglycine and sarcosine, choline is the major one-carbon donor for methionine regeneration from homocysteine. Methionine is primarily used for essential methylation processes via S-adenosyl-methionine.

Clinical impact

CF patients with exocrine pancreas insufficiency frequently develop choline deficiency, due to loss of bile Ptd’Cho via feces. ~ 50% (11–12 g) of hepatic Ptd’Cho is daily secreted into the duodenum. Its re-uptake requires cleavage to lyso-Ptd’Cho by pancreatic and small intestinal phospholipases requiring alkaline environment. Impaired CFTR-dependent bicarbonate secretion, however, results in low duodenal pH, impaired phospholipase activity, fecal Ptd’Cho loss and choline deficiency. Low plasma choline causes decreased availability for parenchymal Ptd’Cho metabolism, impacting on organ functions. Choline deficiency results in hepatic choline/Ptd’Cho accretion from lung tissue via high density lipoproteins, explaining the link between choline deficiency and lung function. Hepatic Ptd’Cho synthesis from phosphatidylethanolamine by phosphatidylethanolamine-N-methyltransferase (PEMT) partly compensates for choline deficiency, but frequent single nucleotide polymorphisms enhance choline requirement. Additionally, small intestinal bacterial overgrowth (SIBO) frequently causes intraluminal choline degradation in CF patients prior to its absorption. As adequate choline supplementation was clinically effective and adult as well as pediatric CF patients suffer from choline deficiency, choline supplementation in CF patients of all ages should be evaluated.

Farrell PM (2008) The prevalence of cystic fibrosis in the European Union. J Cyst Fibros 7:450–453PubMed

Festini F, Taccetti G, Repetto T, Mannini C, Neri S, Bisogni S, de Martino M (2008) Incidence of cystic fibrosis in the Albanian population. Pediatr Pulmonol 43:1124–1129. https://doi.org/10.1002/ppul.20920CrossRefPubMed

Naehrig S, Chao C-M, Naehrlich L (2017) Mukoviszidose—diagnose und Therapie (Cystic fibrosis—diagnosis and treatment). Dtsch Arztebl Int 114:564–574. https://doi.org/10.3238/arztebl.2017.0564CrossRefPubMedPubMedCentral

Kosorok MR, Wei WH, Farrell PM (1996) The incidence of cystic fibrosis. Stat Med 15:449–462PubMed

Raskin S, Pereira-Ferrari L, Reis FC, Abreu F, Marostica P, Rozov T, Cardieri J, Ludwig N, Valentin L, Rosario-Filho NA, Camargo Neto E, Lewis E, Giugliani R, Diniz EM, Culpi L, Phillip JA 3rd, Chakraborty R (2008) Incidence of cystic fibrosis in five different states of Brazil as determined by screening of p. F508del, mutation at the CFTR gene in newborns and patients. J Cyst Fibros 7:15–22PubMed

Scotet V, Duguépéroux I, Saliou P, Rault G, Roussey M, Audrézet MP, Férec C (2012) Evidence for decline in the incidence of cystic fibrosis: a 35-year observational study in Brittany. France Orphanet J Rare Dis 7:14. https://doi.org/10.1186/1750-1172-7-14CrossRefPubMed

Hoo AF, Thia LP, Nguyen TT, Bush A, Chudleigh J, Lum S, Ahmed D, Balfour Lynn I, Carr SB, Chavasse RJ, Costeloe KL, Price J, Shankar A, Wallis C, Wyatt HA, Wade A, Stocks J, Collaboration LCF (2012) Lung function is abnormal in 3-month-old infants with cystic fibrosis diagnosed by newborn screening. Thorax 67:874–881PubMed

Korten I, Kieninger E, Yammine S, Cangiano G, Nyilas S, Anagnostopoulou P, Singer F, Kuehni CE, Regamey N, Frey U, Casaulta C, Spycher BD, Latzin P (2019) Respiratory rate in infants with cystic fibrosis throughout the first year of life and association with lung clearance index measured shortly after birth. J Cyst Fibros 18:118–126. https://doi.org/10.1016/j.jcf.2018.07.002CrossRefPubMed

Bernhard W, Poets CF, Franz AR (2019) Choline and choline-related nutrients in regular and preterm infant growth. Eur J Nutr 58:931–945PubMed

10.

Festini F, Taccetti G, Repetto T, Reali MF, Campana S, Mergni G, Marianelli L, de Martino M (2005) Gestational and neonatal characteristics of children with cystic fibrosis: a cohort study. J Pediatr 147(3):316–320PubMed

11.

Ramos KJ, Sack CS, Mitchell KH, Goss CH, Starr JR (2017) Cystic fibrosis is associated with adverse neonatal outcomes in Washington State, 1996–2013. J Pediatr 180:206–211.e1. https://doi.org/10.1016/j.jpeds.2016.09.069CrossRefPubMed

12.

Schlüter DK, Griffiths R, Adam A, Akbari A, Heaven ML, Paranjothy S, Nybo Andersen AM, Carr SB, Pressler T, Diggle PJ, Taylor-Robinson D (2019) Impact of cystic fibrosis on birthweight: a population based study of children in Denmark and Wales. Thorax 74:447–454. https://doi.org/10.1136/thoraxjnl-2018-211706CrossRefPubMed

13.

Sathe M, Houwen R (2017) Meconium ileus in cystic fibrosis. J Cyst Fibros 16(Suppl 2):S32–S39. https://doi.org/10.1016/j.jcf.2017.06.007CrossRefPubMed

14.

Colombo C, Battezzati PM, Crosignani A, Morabito A, Costantini D, Padoan R, Giunta A (2002) Liver disease in cystic fibrosis: a prospective study on incidence, risk factors, and outcome. Hepatology 36:1374–1382PubMed

15.

Williams SM, Goodman R, Thomson R, Mchugh K, Lindsell DRM (2002) Ultrasound evaluation of liver disease in cystic fibrosis as part of an annual assessment clinic: a 9-year review. Clin Radiol 57:365–370PubMed

16.

Debray D, Kelly D, Houwen R, Strandvik B, Colombo C (2011) Best practice guidance for the diagnosis and management of cystic fibrosis—associated liver disease. J Cyst Fibros 10(Suppl 2):29–36

17.

Gaskin K, Gurwitz D, Durie P, Corey M, Levison H, Forstner G (1982) Improved respiratory prognosis in patients with cystic fibrosis with normal fat absorption. J Pediatr 100:857–862PubMed

18.

Innis SM, Davidson AG, Melynk S (2007) James SJ (2007) Choline-related supplements improve abnormal plasma methionine-homocysteine metabolites and glutathione status in children with cystic fibrosis. Am J Clin Nutr 85(3):702–708PubMed

19.

Grothe J, Riethmüller J, Tschürtz SM, Raith M, Pynn CJ, Stoll D, Bernhard W (2015) Plasma phosphatidylcholine alterations in cystic fibrosis patients: impaired metabolism and correlation with lung function and inflammation. Cell Physiol Biochem 35:1437–1453PubMed

20.

Bernhard W, Lange R, Graepler-Mainka U, Engel C, Machann J, Hund V, Shunova A, Hector A, Riethmüller J (2019) Choline supplementation in systic fibrosis-the metabolic and clinical impact. Nutrients. https://doi.org/10.3390/nu11030656CrossRefPubMedPubMedCentral

21.

Chen AH, Innis SM, Davidson AG, James SJ (2005) Phosphatidylcholine and lysophosphatidylcholine excretion is increased in children with cystic fibrosis and is associated with plasma homocysteine, S-adenosylhomocysteine, and S-adenosylmethionine. Am J Clin Nutr 81:686–691PubMed

22.

Middleton PG, Mall MA, Dřevínek P, Lands LC, McKone EF, Polineni D, Ramsey BW, Taylor-Cousar JL, Tullis E, Vermeulen F, Marigowda G, McKee CM, Moskowitz SM, Nair N, Savage J, Simard C, Tian S, Waltz D, Xuan F, Rowe SM, Jain R, VX17-445-102 Study Group (2019) Elexacaftor-tezacaftor-ivacaftor for cystic fibrosis with a single Phe508del allele. N Engl J Med 381:1809–1819. https://doi.org/10.1056/NEJMoa1908639CrossRefPubMedPubMedCentral

23.

Rosenfeld M, Wainwright CE, Higgins M, Wang LT, McKee C, Campbell D, Tian S, Schneider J, Cunningham S, Davies JC, ARRIVAL study group (2018) Ivacaftor treatment of cystic fibrosis in children aged 12 to <24 months and with a CFTR gating mutation (ARRIVAL): a phase 3 single-arm study. Lancet Respir Med 6:545–553. https://doi.org/10.1016/S2213-2600(18)30202-9CrossRefPubMedPubMedCentral

24.

Innis SM, Hasman D (2006) Evidence of choline depletion and reduced betaine and dimethylglycine with increased homocysteine in plasma of children with cystic fibrosis. J Nutr 136:2226–2231PubMed

25.

Riordan JR, Rommens JM, Kerem B, Alon N, Rozmahel R, Grzelczak Z, Zielenski J, Lok S, Plavsic N, Chou JL, Drumm M, Nuzzi MI, Collins FS, Tsui L-C (1989) Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 245(4922):1066–1073. https://doi.org/10.1126/science.2475911CrossRefPubMed

26.

Boujaoude LC, Bradshaw-Wilder C, Mao C, Cohn J, Ogretmen B, Hannun YA, Obeid LM (2001) Cystic fibrosis transmembrane regulator regulates uptake of sphingoid base phosphates and lysophosphatidic acid: modulation of cellular activity of sphingosine 1-phosphate. J Biol Chem 276:35258–35264PubMed

27.

Borowitz D (2015) CFTR, bicarbonate, and the pathophysiology of cystic fibrosis. Pediatr Pulmonol 50(Suppl 40):S24–S30. https://doi.org/10.1002/ppul.23247CrossRefPubMed

28.

Linsdell P, Hanrahan JW (1998) Glutathione permeability of CFTR. Am J Physiol 275:C323–C326. https://doi.org/10.1152/ajpcell.1998.275.1.C323CrossRefPubMed

29.

Kogan I, Ramjeesingh M, Li C, Kidd JF, Wang Y, Leslie EM, Cole SP, Bear CE (2003) CFTR directly mediates nucleotide-regulated glutathione flux. EMBO J 22:1981–1989PubMedPubMedCentral

30.

Corvol H, Blackman SM, Boëlle PY, Gallins PJ, Pace RG, Stonebraker JR, Accurso FJ, Clement A, Collaco JM, Dang H, Dang AT, Franca A, Gong J, Guillot L, Keenan K, Li W, Lin F, Patrone MV, Raraigh KS, Sun L, Zhou YH, O'Neal WK, Sontag MK, Levy H, Durie PR, Rommens JM, Drumm ML, Wright FA, Strug LJ, Cutting GR, Knowles MR (2015) Genome-wide association meta-analysis identifies five modifier loci of lung disease severity in cystic fibrosis. Nat Commun 6:8382. https://doi.org/10.1038/ncomms9382CrossRefPubMed

31.

da Costa KA, Kozyreva OG, Song J, Galanko JA, Fischer LM, Zeisel SH (2006) Common genetic polymorphisms affect the human requirement for the nutrient choline. FASEB J 20:1336–1344PubMed

32.

Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline (1998) Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. National Academies Press (US), Washington (DC)

33.

EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) (2016) Dietary reference values for choline. EFSA Journal 14:4484. https://doi.org/10.2903/j.efsa.2016.4484CrossRef

34.

Koc H, Mar MH, Ranasinghe A, Swenberg JA, Zeisel SH (2002) Quantitation of choline and its metabolites in tissues and foods by liquid chromatography/electrospray ionization-isotope dilution mass spectrometry. Anal Chem 74:4734–4740PubMed

35.

Bernhard W, Haagsman HP, Tschernig T, Poets CF, Postle AD, van Eijk ME, von der Hardt H (1997) Conductive airway surfactant: surface-tension function, biochemical composition, and possible alveolar origin. Am J Respir Cell Mol Biol 17:41–50PubMed

36.

Ebisuzaki K, Williams JN Jr (1955) Preparation and partial purification of soluble choline dehydrogenase from liver mitochondria. Biochem J 60:644–646PubMedPubMedCentral

37.

Rothschild HA, Barron ES (1954) The oxidation of betaine aldehyde by betaine aldehyde dehydrogenase. J Biol Chem 209:511–523PubMed

38.

Pynn CJ, Henderson NG, Clark H, Koster G, Bernhard W, Postle AD (2011) Specificity and rate of human and mouse liver and plasma phosphatidylcholine synthesis analyzed in vivo. J Lipid Res 52:399–407. https://doi.org/10.1194/jlr.D011916CrossRefPubMedPubMedCentral

39.

Corbin KD, Abdelmalek MF, Spencer MD, da Costa KA, Galanko JA, Sha W, Suzuki A, Guy CD, Cardona DM, Torquati A, Diehl AM, Zeisel SH (2013) Genetic signatures in choline and 1-carbon metabolism are associated with the severity of hepatic steatosis. FASEB J 27:1674–1689. https://doi.org/10.1096/fj.12-219097CrossRefPubMedPubMedCentral

40.

Resseguie ME, da Costa KA, Galanko JA, Patel M, Davis IJ, Zeisel SH (2011) Aberrant estrogen regulation of PEMT results in choline deficiency-associated liver dysfunction. J Biol Chem 286:1649–1658. https://doi.org/10.1074/jbc.M110.106922CrossRefPubMed

41.

Liebscher G (1895) Untersuchungen über die Bestimmung des Düngerbedürfnisses der Ackerböden und Kulturpflanzen. Journal für Landwirtschaft 43:49–216

42.

Branca F, Ferrari M (2002) Impact of micronutrient deficiencies on growth: the stunting syndrome. Ann Nutr Metab 46(Suppl 1):8–17PubMed

43.

Zeisel SH (2006) The fetal origins of memory: the role of dietary choline in optimal brain development. J Pediatr 149(5 Suppl):131–136

44.

Turck D, Braegger CP, Colombo C, Declercq D, Morton A, Pancheva R, Robberecht E, Stern M, Strandvik B, Wolfe S, Schneider SM, Wilschanski M (2016) ESPEN-ESPGHAN-ECFS guidelines on nutrition care for infants, children, and adults with cystic fibrosis. Clin Nutr 35:557–577. https://doi.org/10.1016/j.clnu.2016.03.004CrossRefPubMed

45.

Groleau V, Schall JI, Dougherty KA, Latham NE, Maqbool A, Mascarenhas MR, Stallings VA (2014) Effect of a dietary intervention on growth and energy expenditure in children with cystic fibrosis. J Cyst Fibros 13:572–578. https://doi.org/10.1016/j.jcf.2014.01.009CrossRefPubMedPubMedCentral

46.

Schall JI, Mascarenhas MR, Maqbool A, Dougherty KA, Elci O, Wang DJ, Altes TA, Hommel KA, Shaw W, Moore J, Stallings VA (2016) Choline supplementation with a structured lipid in children with cystic fibrosis: a randomized placebo-controlled trial. J Pediatr Gastroenterol Nutr 62:618–626. https://doi.org/10.1097/MPG.0000000000001004CrossRefPubMedPubMedCentral

47.

Alshaikh B, Schall JI, Maqbool A, Mascarenhas M, Bennett MJ, Stallings VA (2016) Choline supplementation alters some amino acid concentrations with no change in homocysteine in children with cystic fibrosis and pancreatic insufficiency. Nutr Res 36:418–429. https://doi.org/10.1016/j.nutres.2015.12.014CrossRefPubMed

48.

Kohlmeier M, da Costa KA, Fischer LM, Zeisel SH (2005) Genetic variation of folate-mediated one-carbon transfer pathway predicts susceptibility to choline deficiency in humans. Proc Natl Acad Sci USA 102:16025–16030PubMedPubMedCentral

49.

Ueland PM (2011) Choline and betaine in health and disease. J Inherit Metab Dis 34:3–15. https://doi.org/10.1007/s10545-010-9088-4CrossRefPubMed

50.

da Costa KA, Corbin KD, Niculescu MD, Galanko JA, Zeisel SH (2014) Identification of new genetic polymorphisms that alter the dietary requirement for choline and vary in their distribution across ethnic and racial groups. FASEB J 28:2970–2978PubMedPubMedCentral

51.

Ganz AB, Cohen VV, Swersky CC, Stover J, Vitiello GA, Lovesky J, Chuang JC, Shields K, Fomin VG, Lopez YS, Mohan S, Ganti A, Carrier B, Malysheva OV, Caudill MA (2017) Genetic variation in choline-metabolizing enzymes alters choline metabolism in young women consuming choline intakes meeting current recommendations. Int J Mol Sci 18:252PubMedCentral

52.

Bernhard W, Böckmann K, Maas C, Mathes M, Hövelmann J, Shunova A, Hund V, Schleicher E, Poets CF, Franz AR (2019) Combined choline and DHA supplementation: a randomized controlled trial. Eur J Nutr. https://doi.org/10.1007/s00394-019-01940-7CrossRefPubMed

53.

Lockman PR, Allen DD (2002) The transport of choline. Drug Dev Ind Pharm 28:749–771PubMed

54.

Hollenbeck CB (2012) An introduction to the nutrition and metabolism of choline. Cent Nerv Syst Agents Med Chem 12:100–113PubMed

55.

Santos T, Mesquita R, Martins E, Silva J, Saldanha C (2003) Effects of choline on hemorheological properties and NO metabolism of human erythrocytes. Clin Hemorheol Microcirc 29:41–51PubMed

56.

Martin K (1968) Concentrative accumulation of choline by human erythrocytes. J Gen Physiol 51:497–516PubMedPubMedCentral

57.

Traiffort E, Ruat M, O'Regan S, Meunier FM (2005) Molecular characterization of the family of choline transporter-like proteins and their splice variants. J Neurochem 92:1116–1125. https://doi.org/10.1111/j.1471-4159.2004.02962CrossRefPubMed

58.

Fervenza FC, Meredith D, Ellory JC, Hendry BM (1991) Abnormal erythrocyte choline transport in patients with chronic renal failure. Clin Sci (Lond) 80:137–141

59.

Butterfield DA, Nicholas MM, Markesbery WR (1985) Evidence for an increased rate of choline efflux across erythrocyte membranes in Alzheimer's disease. Neurochem Res 10:909–918PubMed

60.

Jope RS, Jenden DJ, Ehrlich BE, Diamond JM, Gosenfeld LF (1980) Erythrocyte choline concentrations are elevated in manic patients. Proc Natl Acad Sci USA 77:6144–6146PubMedPubMedCentral

61.

Kirk K, Wong HY, Elford BC, Newbold CI, Ellory JC (1991) Enhanced choline and Rb+ transport in human erythrocytes infected with the malaria parasite Plasmodium falciparum. Biochem J 278:521–525PubMedPubMedCentral

62.

Bernhard W, Raith M, Kunze R, Koch V, Heni M, Maas C, Abele H, Poets CF, Franz AR (2015) Choline concentrations are lower in postnatal plasma of preterm infants than in cord plasma. Eur J Nutr 54:733–741. https://doi.org/10.1007/s00394-014-0751-7CrossRefPubMed

63.

Fujii T, Mashimo M, Moriwaki Y, Misawa H, Ono S, Horiguchi K, Kawashima K (2017) Expression and function of the cholinergic system in immune cells. Front Immunol 8:1085. https://doi.org/10.3389/fimmu.2017.01085CrossRefPubMedPubMedCentral

64.

Bernhard W, Gesche J, Raith M, Poets CF (2016) Phosphatidylcholine kinetics in neonatal rat lungs and the effects of rhuKGF and betamethasone. Am J Physiol Lung Cell Mol Physiol 310:L955–L963. https://doi.org/10.1152/ajplung.00010.2016CrossRefPubMed

65.

Holmes-McNary MQ, Loy R, Mar MH, Albright CD, Zeisel SH (1997) Apoptosis is induced by choline deficiency in fetal brain and in PC12 cells. Brain Res Dev Brain Res 101:9–16PubMed

66.

Zeisel SH (1981) Dietary choline: biochemistry, physiology, and pharmacology. Annu Rev Nutr 1:95–121PubMed

67.

Li Z, Vance DE (2008) Phosphatidylcholine and choline homeostasis. J Lipid Res 49:1187–1194PubMed

68.

Dombrowsky H, Clark GT, Rau GA, Bernhard W, Postle AD (2003) Molecular species compositions of lung and pancreas phospholipids in the cftr(tm1HGU/tm1HGU) cystic fibrosis mouse. Pediatr Res 53:447–454PubMed

69.

Alvaro D, Angelico M, Cantafora A, Di Biase A, De Santis A, Bracci F, Minervini G, Ginanni Corradini S, Attili AF, Capocaccia L (1986) Biliary secretion of phosphatidylcholine and its molecular species in cholecystectomized T-tube patients: effects of bile acid hydrophilicity. Biochem Med Metab Biol 36:125–135. https://doi.org/10.1016/0885-4505(86)90116-7CrossRefPubMed

70.

Bernhard W, Bertling A, Dombrowsky H, Vieten G, Rau GA, von der Hardt H, Freihorst J (2001) Metabolism of surfactant phosphatidylcholine molecular species in cftrtm1HGU/tm1HGU mice compared to MF-1 mice. Exp Lung Res 27:349–366PubMed

71.

Bernhard W, Pynn CJ, Jaworski A, Rau GA, Hohlfeld JM, Freihorst J, Poets CF, Stoll D, Postle AD (2004) Mass spectrometric analysis of surfactant metabolism in human volunteers using deuteriated choline. Am J Respir Crit Care Med 170:54–58PubMed

72.

Bernhard W, Maas C, Shunova A, Mathes M, Böckmann K, Bleeker C, Vek J, Poets CF, Schleicher E, Franz AR (2018) Transport of long-chain polyunsaturated fatty acids in preterm infant plasma is dominated by phosphatidylcholine. Eur J Nutr 57:2105–2112PubMed

73.

Slow S, Garrow TA (2006) Liver choline dehydrogenase and kidney betaine-homocysteine methyltransferase expression are not affected by methionine or choline intake in growing rats. J Nutr 136:2279–2283PubMed

74.

Wu BT, Dyer RA, King DJ, Richardson KJ, Innis SM (2012) Early second trimester maternal plasma choline and betaine are related to measures of early cognitive development in term infants. PLoS ONE 7:e43448. https://doi.org/10.1371/journal.pone.0043448CrossRefPubMedPubMedCentral

75.

Födinger M, Hörl WH, Sunder-Plassmann G (2000) Molecular biology of 5,10-methylenetetrahydrofolate reductase. J Nephrol 13:20–33PubMed

76.

Nefic H, Mackic-Djurovic M, Eminovic I (1298A) The frequency of the 677C>T and 1298A>C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene in the population. Med Arch 72:164–169. https://doi.org/10.5455/medarh.2018.72.164-169CrossRefPubMedPubMedCentral

77.

Tjong E, Mohiuddin SS (2020) Biochemistry, Tetrahydrofolate. In: StatPearls, Treasure Island, FL StatPearls Publishing: https://www.ncbi.nlm.nih.gov/books/NBK539712/ Accessed 2019 Apr 21

78.

Obeid R (2013) The metabolic burden of methyl donor deficiency with focus on the betaine homocysteine methyltransferase pathway. Nutrients 5:3481–3495PubMedPubMedCentral

79.

Craciunescu CN, Johnson AR, Zeisel SH (2010) Dietary choline reverses some, but not all, effects of folate deficiency on neurogenesis and apoptosis in fetal mouse brain. J Nutr 140:1162–1166PubMedPubMedCentral

80.

Garrow TA (1996) Purification, kinetic properties, and cDNA cloning of mammalian betaine-homocysteine methyltransferase. J Biol Chem 271:22831–22838PubMed

81.

Li F, Feng Q, Lee C, Wang S, Pelleymounter LL, Moon I, Eckloff BW, Wieben ED, Schaid DJ, Yee V, Weinshilboum RM (2008) Human betaine-homocysteine methyltransferase (BHMT) and BHMT2: common gene sequence variation and functional characterization. Mol Genet Metab 94:326–335. https://doi.org/10.1016/j.ymgme.2008.03.013CrossRefPubMedPubMedCentral

82.

Porter DH, Cook RJ, Wagner C (1985) Enzymatic properties of dimethylglycine dehydrogenase and sarcosine dehydrogenase from rat liver. Arch Biochem Biophys 243:396–407PubMed

83.

Allen RH, Stabler SP, Lindenbaum J (1993) Serum betaine, N, N-dimethylglycine and N-methylglycine levels in patients with cobalamin and folate deficiency and related inborn errors of metabolism. Metabolism 42:1448–1460PubMed

84.

Mudd SH, Brosnan JT, Brosnan ME, Jacobs RL, Stabler SP, Allen RH, Vance DE, Wagner C (2007) Methyl balance and transmethylation fluxes in humans. Am J Clin Nutr 85:19–25PubMed

85.

Yan J, Jiang X, West AA, Perry CA, Malysheva OV, Devapatla S, Pressman E, Vermeylen F, Stabler SP, Allen RH, Caudill MA (2012) Maternal choline intake modulates maternal and fetal biomarkers of choline metabolism in humans. Am J Clin Nutr 95:1060–1071PubMed

86.

Wyss M, Kaddurah-Daouk R (2000) Creatine and creatinine metabolism. Physiol Rev 80:1107–1213PubMed

87.

Innis SM, Davidson AG (2008) Cystic fibrosis and nutrition: linking phospholipids and essential fatty acids with thiol metabolism. Annu Rev Nutr 28:55–72. https://doi.org/10.1146/annurev.nutr.27.061406.093625CrossRefPubMed

88.

Gao L, Kim KJ, Yankaskas JR, Forman HJ (1999) Abnormal glutathionine transport in cystic fibrosis airway epithelia. Am J Physio 277:L113–L118

89.

Cantlin AM, Hubbard RC, Crystal RG (1989) Glutathione deficiency in epithelial lining fluid of the lower respiratory tract in idiopathic pulmonary fibrosis. Am Rev Resp Dis 139:370–372

90.

Roum JH, Buhl R, McElvaney NG, Borok Z, Crystal RG (1993) Systemic deficiency of glutathione in cystic fibrosis. J Appl Physiol 75:2419–2424PubMed

91.

Janosík M, Kery V, Gaustadnes M, Maclean KN, Kraus JP (2001) Regulation of human cystathionine beta-synthase by S-adenosyl-L-methionine: evidence for two catalytically active conformations involving an autoinhibitory domain in the C-terminal region. Biochemistry 40:10625–10633PubMed

92.

Steegborn C, Clausen T, Sondermann P, Jacob U, Worbs M, Marinkovic S, Huber R, Wahl MC (1999) Kinetics and inhibition of recombinant human cystathionine gamma-lyase. Toward the rational control of transsulfuration. J Biol Chem 274:12675–12684PubMed

93.

Waters DL, Dorney SF, Gaskin KJ, Gruca MA, O'Halloran M, Wilcken B (1990) Pancreatic function in infants identified as having cystic fibrosis in a neonatal screening program. N Engl J Med 322:303–308PubMed

94.

Cipolli M, Castellani C, Wilcken B, Massie J, McKay K, Gruca M, Tamanini A, Assael MB, Gaskin K (2007) Pancreatic phenotype in infants with cystic fibrosis identified by mutation screening. Arch Dis Child 92:842–846PubMedPubMedCentral

95.

Wilschanski M, Novak I (2013) The cystic fibrosis of exocrine pancreas. Cold Spring Harb Perspect Med 3:a009746PubMedPubMedCentral

96.

Rick W (1964) Funktion des Pankreas bei zystischer Pankreasfibrose. Verh Dtsch Ges Inn Med 42:2158

97.

Wang Z, Wang T, Petrovic S, Tuo B, Riederer B, Barone S, Lorenz JN, Seidler U, Aronson PS, Soleimani M (2005) Renal and intestinal transport defects in Slc26a6-null mice. Am J Physiol Cell Physiol 288:C957–C965. https://doi.org/10.1152/ajpcell.00505.2004CrossRefPubMed

98.

Kunzelmann K, Schreiber R, Hadorn HB (2017) Bicarbonate in cystic fibrosis. J Cyst Fibros 16:653–662. https://doi.org/10.1016/j.jcf.2017.06.005CrossRefPubMed

99.

Choi JY, Muallem D, Kiselyov K, Lee MG, Thomas PJ, Muallem S (2001) Aberrant CFTR-dependent HCO3—transport in mutations associated with cystic fibrosis. Nature 410:94–97PubMedPubMedCentral

100.

Quinton PM (2001) The neglected ion: HCO₃⁻. Nat Med 7:292–293PubMed

101.

Quinton PM (2008) Impaired bicarbonate secretion causes mucoviscidosis in cystic fibrosis. Lancet 372:415–417PubMed

102.

Garland AL, Walton WG, Coakley RD, Tan CD, Gilmore RC, Hobbs CA, Tripathy A, Clunes LA, Bencharit S, Stutts MJ, Betts L, Redinbo MR, Tarran R (2013) Molecular basis for pH-dependent mucosal dehydration in cystic fibrosis airways. Proc Natl Acad Sci USA 110:15973–15978. https://doi.org/10.1073/pnas.1311999110CrossRefPubMedPubMedCentral

103.

Abou Alaiwa MH, Beer AM, Pezzulo AA, Launspach JL, Horan RA, Stoltz DA, Starner TD, Welsh MJ, Zabner J (2014) Neonates with cystic fibrosis have a reduced nasal liquid pH; a small pilot study. J Cyst Fibros 13:373–377PubMedPubMedCentral

104.

Park HW, Nam JH, Kim JY, Namkung W, Yoon JS, Lee JS, Kim KS, Venglovecz V, Gray MA, Kim KH, Lee MG (2010) Dynamic regulation of CFTR bicarbonate permeability by [Cl-]i and its role in pancreatic bicarbonate secretion. Gastroenterology 139:620–631. https://doi.org/10.1053/j.gastro.2010.04.004CrossRefPubMed

105.

Shwachman H, Patterson P, Farber S (1950) Significance of altered viscosity of duodenal content in pancreatic fibrosis (mucoviscidosis). AMA Am J Dis Child 80:864–865PubMed

106.

Chen EY, Yang N, Quinton PM, Chin WC (2010) A new role for bicarbonate in mucus formation. Am J Physiol Lung Cell Mol Physiol 299:L542–L549. https://doi.org/10.1152/ajplung.00180.2010CrossRefPubMedPubMedCentral

107.

Pezzulo AA, Tang XX, Hoegger MJ, Alaiwa MH, Ramachandran S, Moninger TO, Karp PH, Wohlford-Lenane CL, Haagsman HP, van Eijk M, Bánfi B, Horswill AR, Stoltz DA, McCray PB Jr, Welsh MJ, Zabner J (2012) Reduced airway surface pH impairs bacterial killing in the porcine cystic fibrosis lung. Nature 487:109–113PubMedPubMedCentral

108.

Yang N, Garcia MA, Quinton PM (2013) Normal mucus formation requires cAMP-dependent HCO3- secretion and Ca2+-mediated mucin exocytosis. J Physiol 591:4581–4593. https://doi.org/10.1113/jphysiol.2013.257436CrossRefPubMedPubMedCentral

109.

Nilsson Å, Duan RD (2019) Pancreatic and mucosal enzymes in choline phospholipid digestion. Am J Physiol Gastrointest Liver Physiol 316:G425–G445. https://doi.org/10.1152/ajpgi.00320.2018CrossRefPubMed

110.

Roy CC, Weber AM, Lepage G, Smith L, Levy E (1988) Digestive and absorptive phase anomalies associated with the exocrine pancreatic insufficiency of cystic fibrosis. J Pediatr Gastroenterol Nutr 7(Suppl 1):S1–S7PubMed

111.

Marteau C, Sastre B, Iconomidis N, Portugal H, Pauli AM, Gérolami A (1990) pH regulation in human gallbladder bile: study in patients with and without gallstones. Hepatology 11:997–1002PubMed

112.

Sutor DJ, Wilkie LI (1976) Diurnal variations in the pH of pathological gallbladder bile. Gut 17:971–974PubMedPubMedCentral

113.

Youngberg CA, Berardi RR, Howatt WF, Hyneck ML, Amidon GL, Meyer JH, Dressman JB (1987) Comparison of gastrointestinal pH in cystic fibrosis and healthy subjects. Dig Dis Sci 32:472–480PubMed

114.

Maurer JM, Schellekens RC, van Rieke HM, Wanke C, Iordanov V, Stellaard F, Wutzke KD, Dijkstra G, van der Zee M, Woerdenbag HJ, Frijlink HW, Kosterink JG (2015) Gastrointestinal pH and transit time profiling in healthy volunteers using the IntelliCap system confirms Ileo-Colonic release of ColoPulse tablets. PLoS ONE 10(7):e0129076. https://doi.org/10.1371/journal.pone.0129076CrossRefPubMedPubMedCentral

115.

Barraclough M, Taylor CJ (1996) Twenty-four hour ambulatory gastric and duodenal pH profiles in cystic fibrosis: effect of duodenal hyperacidity on pancreatic enzyme function and fat absorption. J Pediatr Gastroenterol Nutr 23:45–50PubMed

116.

Murakami M, Sato H, Miki Y, Yamamoto K, Taketomi Y (2015) A new era of secreted phospholipase A2. J Lipid Res 56:1248–1261. https://doi.org/10.1194/jlr.R058123CrossRefPubMedPubMedCentral

117.

Venuti E, Shishmarev D, Kuchel PW, Dutt S, Blumenthal CS, Gaskin KJ (2017) Bile salt stimulated lipase: inhibition by phospholipids and relief by phospholipase A2. J Cyst Fibros 16:763–770PubMed

118.

Proesmans M, De Boeck K (2003) Omeprazole, a proton pump inhibitor, improves residual steatorrhoea in cystic fibrosis patients treated with high dose pancreatic enzymes. Eur J Pediatr 162:760–763PubMed

119.

Whitcomb DC, Lowe ME (2007) Human pancreatic digestive enzymes. Dig Dis Sci 52:1–17PubMed

120.

Duane WC, Ginsberg RL, Bennion LJ (1976) Effects of fasting on bile acid metabolism and biliary lipid composition in man. J Lipid Res 17:211–219PubMed

121.

Haber GB, Heaton KW (1979) Lipid composition of bile in diabetics and obesity matched controls. Gut 20:518–522PubMedPubMedCentral

122.

Muraca M, Vilei MT, Miconi L, Petrin P, Antoniutti M, Pedrazzoli S (1991) A simple method for the determination of lipid composition of human bile. J Lipid Res 32:371–374PubMed

123.

Nicolaou M, Andress EJ, Zolnerciks JK, Dixon PH, Williamson C, Linton KJ (2012) Canalicular ABC transporters and liver disease. J Pathol 226:300–315. https://doi.org/10.1002/path.3019CrossRefPubMed

124.

Kosters A, Kunne C, Looije N, Patel SB, Oude Elferink RP, Groen AK (2006) The mechanism of ABCG5/ABCG8 in biliary cholesterol secretion in mice. J Lipid Res 47:1959–1966. https://doi.org/10.1194/jlr.M500511-JLR200CrossRefPubMed

125.

Northfield TC, Hofmann AF (1975) Biliary lipid output during three meals and an overnight fast. I. Relationship to bile acid pool size and cholesterol saturation of bile in gallstone and control subjects. Gut 16:1–11PubMedPubMedCentral

126.

Li Z, Agellon LB, Allen TM, Umeda M, Jewell L, Mason A, Vance DE (2006) The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis. Cell Metab 3:321–331PubMed

127.

Li Z, Agellon LB, Vance DE (2007) Choline redistribution during adaptation to choline deprivation. J Biol Chem 282:10283–10289PubMed

128.

van Tilbeurgh H, Egloff MP, Martinez C, Rugani N, Verger R, Cambillau C (1993) Interfacial activation of the lipase-procolipase complex by mixed micelles revealed by X-ray crystallography. Nature 362(6423):814–820PubMed

129.

Berg JM, Tymoczko JL, Stryer L (2002) Ed: W H Freeman Biochemistry, 5th edition, New York, ISBN-10: 0–7167–3051–0, https://www.ncbi.nlm.nih.gov/books/NBK22436/#__NBK22436_dtls. Accessed 19 Feb 2020

130.

Greenberger NJ, Isselbacher KJ (1998) Diseases of the gallbladder and bile ducts. In: Fauci A, Braunwald E, Isselbacher KJ, Wilson JD, Martin JB (eds) Harrison’s principles of internal medicine. McGraw-Hill, New York, pp 1725–1726

131.

Molina DK, DiMaio VJM (2012) Normal organ weights in men part II-the brain, lungs, liver, spleen, and kidneys. Am J Forensic Med Pathol 33:368–372PubMed

132.

The LipidWeb (2020) Plasma lipoproteins. https://www.lipidhome.co.uk/lipids/simple/lipoprot/index.htm (Accessed 29.04.2020).

133.

Yao H, Ye J (2008) Long chain acyl-CoA synthetase 3-mediated phosphatidylcholine synthesis is required for assembly of very low density lipoproteins in human hepatoma Huh7 cells. J Biol Chem 283:849–854PubMed

134.

Shi C, Qiao S, Wang S, Wu T, Guang Ji G (2018) Recent progress of lysophosphatidylcholine acyltransferases in metabolic disease and cancer. Int J Clin Exp Med 11:8941–8953

135.

Vance DE (2013) Physiological roles of phosphatidylethanolamine N-methyltransferase. Biochim Biophys Acta 1831:626–632. https://doi.org/10.1016/j.bbalip.2012.07.017CrossRefPubMed

136.

Noga AA, Zhao Y, Vance DE (2002) An unexpected requirement for phosphatidylethanolamine N-methyltransferase in the secretion of very low density lipoproteins. J Biol Chem 277:42358–42365. https://doi.org/10.1074/jbc.M204542200CrossRefPubMed

137.

Löffler G (2013) Gastrointestinaltrakt. In: Löffler G, Petrides PE (eds) Biochemie und Pathobiochemie. Springer, Berlin-Heidelberg-New York, Heidelberg, pp 996–1019

138.

Corbin KD, Zeisel SH (2012) Choline metabolism provides novel insights into nonalcoholic fatty liver disease and its progression. Curr Opin Gastroenterol 28:159–165. https://doi.org/10.1097/MOG.0b013e32834e7b4bCrossRefPubMedPubMedCentral

139.

Zhou J, Ryan AJ, Medh J, Mallampalli RK (2003) Oxidized lipoproteins inhibit surfactant phosphatidylcholine synthesis via calpain-mediated cleavage of CTP:phosphocholine cytidylyltransferase. J Biol Chem 278:37032–37040PubMed

140.

Feingold KR, Grunfeld C (2000) The Effect of Inflammation and Infection on Lipids and Lipoproteins. In: Feingold KR, Anawalt B, Boyce A, et al., eds. Endotext. South Dartmouth (MA): MDText.com, Inc.; 2000. https://www.ncbi.nlm.nih.gov/books/NBK326741/ Accessed 03/06/2020

141.

Freigang S (2016) The regulation of inflammation by oxidized phospholipids. Eur J Immunol 46:1818–1825. https://doi.org/10.1002/eji.201545676CrossRefPubMed

142.

Li Z, Agellon LB, Vance DE (2011) The role of phosphatidylethanolamine methyltransferase in a mouse model of intrahepatic cholestasis. Biochim Biophys Acta 1811:278–283PubMed

143.

Brosnan JT, da Silva RP, Brosnan ME (2011) The metabolic burden of creatine synthesis. Amino Acids 40:1325–1331PubMed

144.

Zeisel S (2017) Choline, other methyl-donors and epigenetics. Nutrients 9:445. https://doi.org/10.3390/nu9050445CrossRefPubMedCentral

145.

Weisberg IS, Jacques PF, Selhub J, Bostom AG, Chen Z, Curtis Ellison R, Eckfeldt JH, Rozen R (1298A) The 1298A–>C polymorphism in methylenetetrahydrofolate reductase (MTHFR): in vitro expression and association with homocysteine. Atherosclerosis 156:409–415PubMed

146.

Bernhard W, Haslam PL, Floros J (2004) From birds to humans: new concepts on airways relative to alveolar surfactant. Am J Respir Cell Mol Biol 30:6–11PubMed

147.

Bernhard W (2016) Regulation of Surfactant-Associated Phospholipid Synthesis and Secretion. Fetal and Neonatal Physiology (Fifth Edition) by: Richard A. Polin, Steven H. Abman, David Rowitch and William E. Benitz, Elsevier, Amsterdam 813 824.

148.

Bridges JP, Ikegami M, Brilli LL, Chen X, Mason RJ, Shannon JM (2010) LPCAT1 regulates surfactant phospholipid synthesis and is required for transitioning to air breathing in mice. J Clin Invest 120:1736–1748. https://doi.org/10.1172/JCI38061CrossRefPubMedPubMedCentral

149.

Borowitz D (1996) The interrelationship of nutrition and pulmonary function in patients with cystic fibrosis. Curr Opin Pulm Med 2:457–461PubMed

150.

Stallings VA, Stark LJ, Robinson KA, Feranchak AP, Quinton H (2008) Evidence-based practice recommendations for nutrition-related management of children and adults with cystic fibrosis and pancreatic insufficiency: results of a systematic review. J Am Diet Assoc 108:832–839PubMed

151.

Trout L, King M, Feng W, Inglis SK, Ballard ST (1998) Inhibition of airway liquid secretion and its effect on the physical properties of airway mucus. Am J Phys 274:L258–L263

152.

Larbig M, Jansen S, Dorsch M, Bernhard W, Ballmann B, Dorin JR, Porteous DJ, von der Hardt H, Steinmetz I, Hedrich HJ, Tuemmler B, Tschernig T (2002) Residual cftr expression varies with age in cftr (tm1Hgu) cystic fibrosis mice: impact on morphology and physiology. Pathobiology 70:89–97PubMed

153.

Mander A, Langton-Hewer S, Bernhard W, Warner JO, Postle AD (2002) Altered phospholipid composition and aggregate structure of lung surfactant is associated with impaired lung function in young children with respiratory infections. Am J Respir Cell Mol Biol 27:714–721PubMed

154.

Holm BA, Keicher L, Liu MY, Sokolowski J (1985) Enhorning G (1991) Inhibition of pulmonary surfactant function by phospholipases. J Appl Physiol 71:317–321

155.

Baile EM (1996) The anatomy and physiology of the bronchial circulation. J Aerosol Med 9:1–6PubMed

156.

Mets OM, Roothaan SM, Bronsveld I, Luijk B, van de Graaf EA, Vink A, de Jong PA (2015) Emphysema is common in lungs of cystic fibrosis lung transplantation patients: a histopathological and computed tomography study. PLoS ONE 10(6):e0128062. https://doi.org/10.1371/journal.pone.0128062CrossRefPubMedPubMedCentral

157.

Perez-Gil J, Weaver TE (2010) Pulmonary surfactant pathophysiology: current models and open questions. Physiology (Bethesda) 25:132–141

158.

Bortnick AE, Favari E, Tao JQ, Francone OL, Reilly M, Zhang Y, Rothblat GH, Bates SR (2003) Identification and characterization of rodent ABCA1 in isolated type II pneumocytes. Am J Physiol Lung Cell Mol Physiol 285:L869–L878PubMed

159.

Zhou J, You Y, Ryan AJ, Mallampalli RK (2004) Upregulation of surfactant synthesis triggers ABCA1-mediated basolateral phospholipid efflux. J Lipid Res 45:1758–1767PubMed

160.

Delvecchio CJ, Bilan P, Nair P, Capone JP (2008) LXR-induced reverse cholesterol transport in human airway smooth muscle is mediated exclusively by ABCA1. Am J Physiol Lung Cell Mol Physiol 295:L949–L957. https://doi.org/10.1152/ajplung.90394.2008CrossRefPubMed

161.

Bates SR, Tao JQ, Collins HL, Francone OL, Rothblat GH (2005) Pulmonary abnormalities due to ABCA1 deficiency in mice. Am J Physiol Lung Cell Mol Physiol 289:L980–L989PubMed

162.

van der Deen M, de Vries EG, Timens W, Scheper RJ, Timmer-Bosscha H, Postma DS (2005) ATP-binding cassette (ABC) transporters in normal and pathological lung. Respir Res 6:59PubMedPubMedCentral

163.

Higgins JA, Fieldsend JK (1987) Phosphatidylcholine synthesis for incorporation into membranes or for secretion as plasma lipoproteins by Golgi membranes of rat liver. J Lipid Res 28:268–278PubMed

164.

Vedhachalam C, Duong PT, Nickel M, Nguyen D, Dhanasekaran P, Saito H, Rothblat GH, Lund-Katz S, Phillips MC (2007) Mechanism of ATP-binding cassette transporter A1-mediated cellular lipid efflux to apolipoprotein A-I and formation of high density lipoprotein particles. J Biol Chem 282:25123–25130PubMed

165.

Lund-Katz S, Lyssenko NN, Nickel M, Nguyen D, Chetty PS, Weibel G, Phillips MC (2013) Mechanisms responsible for the compositional heterogeneity of nascent high density lipoprotein. J Biol Chem 288:23150–23160. https://doi.org/10.1074/jbc.M113.495523CrossRefPubMedPubMedCentral

166.

Lyssenko NN, Nickel M, Tang C, Phillips MC (2013) Factors controlling nascent high-density lipoprotein particle heterogeneity: ATP-binding cassette transporter A1 activity and cell lipid and apolipoprotein AI availability. FASEB J 27:2880–2892. https://doi.org/10.1096/fj.12-216564CrossRefPubMedPubMedCentral

167.

Kennedy MA, Barrera GC, Nakamura K, Baldán A, Tarr P, Fishbein MC, Frank J, Francone OL, Edwards PA (2005) ABCG1 has a critical role in mediating cholesterol efflux to HDL and preventing cellular lipid accumulation. Cell Metab 1:121–131PubMed

168.

Schwartz K, Lawn RM, Wade DP (2000) ABC1 gene expression and ApoA-I-mediated cholesterol efflux are regulated by LXR. Biochem Biophys Res Commun 274:794–802PubMed

169.

Zhang Y, Beyer TP, Bramlett KS, Yao S, Burris TP, Schmidt RJ, Eacho PI, Cao G (2002) Liver X receptor and retinoic X receptor mediated ABCA1 regulation and cholesterol efflux in macrophage cells-messenger RNA measured by branched DNA technology. Mol Genet Metab 77:150–158PubMed

170.

Song C, Kokontis JM, Hiipakka RA, Liao S (1994) Ubiquitous receptor: a receptor that modulates gene activation by retinoic acid and thyroid hormone receptors. Proc Natl Acad Sci USA 91:10809–10813PubMedPubMedCentral

171.

Brunham LR, Kruit JK, Iqbal J, Fievet C, Timmins JM, Pape TD, Coburn BA, Bissada N, Staels B, Groen AK, Hussain MM, Parks JS, Kuipers F, Hayden MR (2006) Intestinal ABCA1 directly contributes to HDL biogenesis in vivo. J Clin Invest 116:1052–1062PubMedPubMedCentral

172.

Bates SR, Tao JQ, Yu KJ, Borok Z, Crandall ED, Collins HL, Rothblat GH (2008) Expression and biological activity of ABCA1 in alveolar epithelial cells. Am J Respir Cell Mol Biol 38:283–292PubMed

173.

Schmitz G, Jabs HU, Assmann G (1983) Densitometry of phosphatidylcholine and sphingomyelin in high-density lipoproteins. Clin Chem 29:1435–1437PubMed

174.

Graham A, Zammit VA, Brindley DN (1988) Fatty acid specificity for the synthesis of triacylglycerol and phosphatidylcholine and for the secretion of very-low-density lipoproteins and lysophosphatidylcholine by cultures of rat hepatocytes. Biochem J 249:727–733PubMedPubMedCentral

175.

Pownall HJ, Hickson-Bick D, Massey JB (1991) Effects of hydrophobicity on turnover of plasma high density lipoproteins labeled with phosphatidylcholine ethers in the rat. J Lipid Res 32:793–800PubMed

176.

Iuliano L, Monticolo R, Straface G, Zullo S, Galli F, Boaz M, Quattrucci S (2009) Association of cholesterol oxidation and abnormalities in fatty acid metabolism in cystic fibrosis. Am J Clin Nutr 90:477–484. https://doi.org/10.3945/ajcn.2009.27757CrossRefPubMed

177.

Agassandian M, Mathur SN, Zhou J, Field FJ, Mallampalli RK (2004) Oxysterols trigger ABCA1-mediated basolateral surfactant efflux. Am J Respir Cell Mol Biol 31:227–233PubMed

178.

Wu MK, Cohen DE (2005) Phosphatidylcholine transfer protein regulates size and hepatic uptake of high-density lipoproteins. Am J Physiol Gastrointest Liver Physiol 289:G1067–G1074PubMed

179.

Kanno K, Wu MK, Scapa EF, Roderick SL, Cohen DE (2007) Structure and function of phosphatidylcholine transfer protein (PC-TP)/StarD2. Biochim Biophys Acta 1771:654–662PubMedPubMedCentral

180.

Ihm J, Quinn DM, Busch SJ, Chataing B, Harmony JA (1982) Kinetics of plasma protein-catalyzed exchange of phosphatidylcholine and cholesteryl ester between plasma lipoproteins. J Lipid Res 23:1328–1341PubMed

181.

Lippiello PM, Waite M (1983) Kinetics and mechanism of phosphatidylcholine and cholesterol exchange between chylomicrons and high-density lipoproteins. Biochem J 215:279–286PubMedPubMedCentral

182.

Nishida HI, Nishida T (1997) Phospholipid transfer protein mediates transfer of not only phosphatidylcholine but also cholesterol from phosphatidylcholine-cholesterol vesicles to high density lipoproteins. J Biol Chem 272:6959–6964PubMed

183.

Aurelia M, Schiumarinia D, Lobertoa N, Bassia R, Tamaninib A, Mancinia G, Tironia M, Munarib S, Cabrinib G, Dechecchib SS (2016) Unravelling the role of sphingolipids in cystic fibrosis lung disease. Chem Phys Lipids 200:94–103. https://doi.org/10.1016/j.chemphyslip.2016.08.002CrossRef

184.

Mérida I, Arranz-Nicolás J, Rodríguez-Rodríguez C, Ávila-Flores A (2019) Diacylglycerol kinase control of protein kinase C. Biochem J 476:1205–1219. https://doi.org/10.1042/BCJ20180620CrossRefPubMed

185.

Brodlie M, McKean MC, Johnson GE, Gray J, Fisher AJ, Corris PA, Lordan JL, Ward C (2010) Ceramide is increased in the lower airway epithelium of people with advanced cystic fibrosis lung disease. Am J Respir Crit Care Med 182:369–375. https://doi.org/10.1164/rccm.200905-0799OCCrossRefPubMed

186.

Li C, Wang A, Wu Y, Gulbins E, Grassmé H, Zhao Z (2019) Acid Sphingomyelinase-ceramide system in bacterial infections. Cell Physiol Biochem 52:280–301. https://doi.org/10.33594/000000021CrossRefPubMed

187.

Grassmé H, Jekle A, Riehle A, Schwarz H, Berger J, Sandhoff K, Kolesnick R, Gulbins E (2001) CD95 signaling via ceramide-rich membrane rafts. J Biol Chem 276:20589–20596PubMed

188.

Stonehouse MJ, Cota-Gomez A, Parker SK, Martin WE, Hankin JA, Murphy RC, Chen W, Lim KB, Hackett M, Vasil AI, Vasil ML (2002) A novel class of microbial phosphocholine-specific phospholipases C. Mol Microbiol 46:661–676PubMed

189.

Becker KA, Riethmüller J, Lüth A, Döring G, Kleuser B, Gulbins E (2010) Acid sphingomyelinase inhibitors normalize pulmonary ceramide and inflammation in cystic fibrosis. Am J Respir Cell Mol Biol 42:716–724. https://doi.org/10.1165/rcmb.2009-0174OCCrossRefPubMed

190.

Teichgräber V, Ulrich M, Endlich N, Riethmüller J, Wilker B, De Oliveira-Munding CC, van Heeckeren AM, Barr ML, von Kürthy G, Schmid KW, Weller M, Tümmler B, Lang F, Grassmé H, Döring G, Gulbins E (2008) Ceramide accumulation mediates inflammation, cell death and infection susceptibility in cystic fibrosis. Nat Med 14:382–391. https://doi.org/10.1038/nm1748CrossRefPubMed

191.

Fillet M, Van Heugen JC, Servais AC, De Graeve J, Crommen J (2002) Separation, identification and quantitation of ceramides in human cancer cells by liquid chromatography-electrospray ionization tandem mass spectrometry. J Chromatogr A 949:225–233. https://doi.org/10.1016/s0021-9673(01)01422-4CrossRefPubMed

192.

Topcu DB, Tugcu G, Ozcan F, Aslan M, Esref S, Hizal MG, Yalcin EE, Ersoz DD, Ozcelik U, Kiper N, Lay I, Oztas Y (2018) Plasma ceramides and sphingomyelins increase in primary ciliary dyskinesia but decrease in cystic fibrosis. Eur Respir J. https://doi.org/10.1183/13993003.congress-2018.PA3424CrossRef

193.

Aureli M, Schiumarini D, Loberto N, Bassi R, Tamanini A, Mancini G, Tironi M, Munari S, Cabrini G, Dechecchi MC, Sonnino S (2016) Unravelling the role of sphingolipids in cystic fibrosis lung disease. Chem Phys Lipids 200:94–103. https://doi.org/10.1016/j.chemphyslip.2016.08.002CrossRefPubMed

194.

Nährlich L, Mainz JG, Adams C, Engel C, Herrmann G, Icheva V, Lauer J, Deppisch C, Wirth A, Unger K, Graepler-Mainka U, Hector A, Heyder S, Stern M, Döring G, Gulbins E, Riethmüller J (2013) Therapy of CF-patients with amitriptyline and placebo-a randomised, double-blind, placebo-controlled phase IIb multicenter, cohort-study. Cell Physiol Biochem 31:505–512. https://doi.org/10.1159/000350071CrossRefPubMed

195.

Becker KA, Riethmüller J, Seitz AP, Gardner A, Boudreau R, Kamler M, Kleuser B, Schuchman E, Caldwell CC, Edwards MJ, Grassmé H, Brodlie M, Gulbins E (2018) Sphingolipids as targets for inhalation treatment of cystic fibrosis. Adv Drug Deliv Rev 133:66–75. https://doi.org/10.1016/j.addr.2018.04.015CrossRefPubMed

196.

Strong TV, Boehm K, Collins FS (1994) Localization of cystic fibrosis transmembrane conductance regulator mRNA in the human gastrointestinal tract by in situ hybridization. J Clin Invest 93:347–354PubMedPubMedCentral

197.

Pratha VS, Hogan DL, Martensson BA, Bernard J, Zhou R, Isenberg JI (2000) Identification of transport abnormalities in duodenal mucosa and duodenal enterocytes from patients with cystic fibrosis. Gastroenterology 118:1051–1060PubMed

198.

Gustafsson JK, Ermund A, Ambort D, Johansson ME, Nilsson HE, Thorell K, Hebert H, Sjövall H, Hansson GC (2012) Bicarbonate and functional CFTR channel are required for proper mucin secretion and link cystic fibrosis with its mucus phenotype. J Exp Med 209:1263–1272PubMedPubMedCentral

199.

Dalzell AM, Freestone NS, Billington D, Heaf DP (1990) Small intestinal permeability and orocaecal transit time in cystic fibrosis. Arch Dis Child 65:585–588PubMedPubMedCentral

200.

Singh VV, Toskes PP (2003) Small bowel bacterial overgrowth: Presentation, diagnosis, and treatment. Curr Gastroenterol Rep 5:365–372PubMed

201.

Fridge JL, Conrad C, Gerson L, Castillo RO, Cox K (2007) Risk factors for small bowel bacterial overgrowth in cystic fibrosis. J Pediatr Gastroenterol Nutr 44:212–218PubMed

202.

Lisowska A, Wojtowicz J, Walkowiak J (2009) Small intestine bacterial overgrowth is frequent in cystic fibrosis: combined hydrogen and methane measurements are required for its detection. Acta Biochim Pol 56:631–634PubMed

203.

Grace E, Shaw C, Whelan K, Andreyev HJ (2013) Review article: small intestinal bacterial overgrowth–prevalence, clinical features, current and developing diagnostic tests, and treatment. Aliment Pharmacol Ther 38:674–688PubMed

204.

O'Brien S, Mulcaby H, Fenlon H, O'Broin M, Casey M, Burke A, FitzGerald MX, Hegarty JE (1993) Intestinal bile acid malabsorption in cystic fibrosis. Gut 34:1137–1141PubMedPubMedCentral

205.

Husebye E (2005) The pathogenesis of gastrointestinal bacterial overgrowth. Chemotherapy 51:1–22PubMed

206.

Norkina O, Burnett TG, De Lisle RC (2004) Bacterial overgrowth in the cystic fibrosis transmembrane conductance regulator null mouse small intestine. Infect Immun 72:6040–6049PubMedPubMedCentral

207.

Burke DG, Fouhy F, Harrison MJ, Rea MC, Cotter PD, O'Sullivan O, Stanton C, Hill C, Shanahan F, Plant BJ, Ross RP (2017) The altered gut microbiota in adults with cystic fibrosis. BMC Microbiol 17:58. https://doi.org/10.1186/s12866-017-0968-8CrossRefPubMedPubMedCentral

208.

Murphy MS, Brunetto AL, Pearson AD, Ghatei MA, Nelson R, Eastham EJ, Bloom SR, Green AA (1992) Gut hormones and gastrointestinal motility in children with cystic fibrosis. Dig Dis Sci 37:187–192PubMed

209.

Gelfond D, Ma C, Semler J, Borowitz D (2012) Intestinal pH and gastrointestinal transit profiles in cystic fibrosis patients measured by wireless motility capsule. Dig Dis Sci 58:2275–2281. https://doi.org/10.1007/s10620-012-2209-1CrossRefPubMed

210.

Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung YM, Wu Y, Schauer P, Smith JD, Allayee H, Tang WH, DiDonato JA, Lusis AJ, Hazen SL (2011) Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472(7341):57–63. https://doi.org/10.1038/nature09922CrossRefPubMedPubMedCentral

211.

Fischer H, Fukuda N, Barbry P, Illek B, Sartori C, Matthay MA (2001) Partial restoration of defective chloride conductance in DeltaF508 CF mice by trimethylamine oxide. Am J Physiol Lung Cell Mol Physiol 281:L52–L57PubMed

212.

Al-Waiz M, Mikov M, Mitchell SC, Smith RL (1992) The exogenous origin of trimethylamine in the mouse. Metabolism 41:135–136PubMed

213.

Shirai K, Fitzharris TJ, Shinomiya M, Muntz HG, Harmony JA, Jackson RL, Quinn DM (1983) Lipoprotein lipase-catalyzed hydrolysis of phosphatidylcholine of guinea pig very low density lipoproteins and discoidal complexes of phospholipid and apolipoprotein: effect of apolipoprotein C-II on the catalytic mechanism. J Lipid Res 24:721–730PubMed

214.

Seidner SR, Jobe AH, Ikegami M, Pettenazzo A, Priestley A, Ruffini L (1988) Lysophosphatidylcholine uptake and metabolism in the adult rabbit lung. Biochim Biophys Acta 961:328–336PubMed

215.

Illingworth DR, Portman OW (1972) The uptake and metabolism of plasma lysophosphatidylcholine in vivo by the brain of squirrel monkeys. Biochem J 130:557–567PubMedPubMedCentral

216.

Li Z, Jiang H, Ding T, Lou C, Bui HH, Kuo MS, Jiang XC (2015) Deficiency in lysophosphatidylcholine acyltransferase 3 reduces plasma levels of lipids by reducing lipid absorption in mice. Gastroenterology 149:1519–1529. https://doi.org/10.1053/j.gastro.2015.07.012CrossRefPubMed

217.

Graf D, Kurz AK, Reinehr R, Fischer R, Kircheis G, Häussinger D (2002) Prevention of bile acid-induced apoptosis by betaine in rat liver. Hepatology 36:829–839. https://doi.org/10.1053/jhep.2002.35536CrossRefPubMed

218.

Craig SA (2004) Betaine in human nutrition. Am J Clin Nutr 80:539–549. https://doi.org/10.1093/ajcn/80.3.539CrossRefPubMed

219.

Smolders L, de Wit NJW, Balvers MGJ, Obeid R, Vissers MMM, Esser D (2019) Natural choline from egg yolk phospholipids is more efficiently absorbed compared with choline bitartrate: outcomes of a randomized trial in healthy adults. Nutrients. https://doi.org/10.3390/nu11112758CrossRefPubMedPubMedCentral

220.

Hirsch MJ, Growdon JH, Wurtman RJ (1978) Relations between dietary choline or lecithin intake, serum choline levels, and various metabolic indices. Metabolism 27:953–960PubMed

221.

Zeisel SH, Growdon JH, Wurtman RJ, Magil SG, Logue M (1980) Normal plasma choline responses to ingested lecithin. Neurology 30:1226–1229PubMed

222.

Cheng W-L, Holmes-McNary MQ, Mar M-H, Lien EL, Zeisel SH (1996) Bioavailability of choline and choline esters from milk in rat pups. Nutritional Biochemistry 7:457–464

223.

Patterson KY, Bhagwat SA, Williams JR, Howe JC, Holden JM (2008) USDA Database for the Choline Content of Common Foods - Release Two. https://data.nal.usda.gov/system/files/Choln02.pdf. Accessed 11/06/2020

224.

Maas C, Franz AR, Shunova A, Mathes M, Bleeker C, Poets CF, Schleicher E, Bernhard W (2017) Choline and polyunsaturated fatty acids in preterm infants' maternal milk. Eur J Nutr 56:1733–1742. https://doi.org/10.1007/s00394-016-1220-2CrossRefPubMed

225.

Holmes-McNary MQ, Cheng WL, Mar MH, Fussell S, Zeisel SH (1996) Choline and choline esters in human and rat milk and in infant formulas. Am J Clin Nutr 64:572–576. https://doi.org/10.1093/ajcn/64.4.572CrossRefPubMed

226.

Lopez C, Ménard O (2011) Human milk fat globules: polar lipid composition and in situ structural investigations revealing the heterogeneous distribution of proteins and the lateral segregation of sphingomyelin in the biological membrane. Colloids Surf B Biointerfaces 83:29–41. https://doi.org/10.1016/j.colsurfb.2010.10.039CrossRefPubMed

Titel: Choline in cystic fibrosis: relations to pancreas insufficiency, enterohepatic cycle, PEMT and intestinal microbiota
verfasst von: Wolfgang Bernhard
Publikationsdatum: 14.08.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Nutrition / Ausgabe 4/2021
Print ISSN: 1436-6207
Elektronische ISSN: 1436-6215
DOI: https://doi.org/10.1007/s00394-020-02358-2

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Choline in cystic fibrosis: relations to pancreas insufficiency, enterohepatic cycle, PEMT and intestinal microbiota

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