Choline, Phosphatidylcholine and Sphingomyelin in Human and Bovine Milk and Infant Formulas

Zeisel, Steven H.; Char, Douglas; Sheard, Nancy F.

doi:10.1093/jn/116.1.50

Cited by 183 publications

(129 citation statements)

References 30 publications

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“…In addition, alkaline SMase is able to hydrolyze dietary SM, which is present substantially in milk, sue may not be counteracted by changing ceramidase activity, because ceramidase activity was not altered eggs, meat, and fish. 19,20 The authors and others have found that the hydrolysis of dietary SM is slow and in this condition. The current results provide a hypothetical explanation for previous findings that the adincomplete and considerable amounts of SM are able to reach the colon, being hydrolyzed locally by ministration of 1,2-dimethylhydrazine, a colon carcinoma carcinogen, was associated with an accumulaSMase.…”

Section: Statistic Analysismentioning

confidence: 93%

Alkaline sphingomyelinase activity is decreased in human colorectal carcinoma

Hertervig¹,

Nilsson²,

Nyberg³

et al. 1997

Cancer

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perimental colon carcinoma in mice, indicating that the abnormal metabolism of sphingomyelin is linked to colon carcinoma development. However, the changes 1 Department of Medicine, Lund University Hospital, Lund, Sweden.in sphingomyelinase (SMase) activity in colon carcinoma have not been directly studied. The authors identified, specifically in the intestine, a distinctive alkaline 2 Research Park Ideon, Swedish Dairies AssociSMase that differs from the known acidic and neutral SMases. The functions and ation, Lund, Sweden.clinical implications of the enzyme are unknown. This study examined the changes 3 Department of Cell Biology, Lund University in all three SMase activities in human colorectal carcinoma. Hospital; Lund, Sweden. METHODS.Tissue samples were taken from colorectal carcinoma and normal mucosa from 18 patients. After homogenization, the activities of acidic, neutral, and alkaline SMase, as well as ceramidase and alkaline phosphatase, were determined. The enzyme activities in cancer tissue were compared with normal tissue from the same patients. RESULTS.In the normal tissue, there is an activity gradient from the ascending colon to the rectum for neutral and alkaline SMases but not for acidic SMase. In colorectal carcinoma, alkaline SMase activity was preferentially decreased by 75%, whereas acidic and neutral SMase activity decreased by 30% and 50%, respectively. No changes could be found for either ceramidase or alkaline phosphatase activity. CONCLUSIONS.Alkaline SMase activity preferentially decreases in human colorectal carcinoma, suggesting a regulatory role of the enzyme in colon mucosa cell proliferation.

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Section: Statistic Analysismentioning

confidence: 93%

Alkaline sphingomyelinase activity is decreased in human colorectal carcinoma

Hertervig¹,

Nilsson²,

Nyberg³

et al. 1997

Cancer

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“…SM is also a dietary component and is mainly present in milk, eggs, meat, and marine products (1,2). Hydrolysis of SM generates ceramide, sphingosine, and sphingosine 1-phosphate that have regulatory effects on numerous cellular functions such as proliferation, differentiation, and apoptosis (3,4).…”

Section: Sphingomyelin (Sm)mentioning

confidence: 99%

Identification of Human Intestinal Alkaline Sphingomyelinase as a Novel Ecto-enzyme Related to the Nucleotide Phosphodiesterase Family

Duan

Bergman

et al. 2003

Journal of Biological Chemistry

128

186

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Alkaline sphingomyelinase (alk-SMase) hydrolyzes dietary sphingomyelin and generates sphingolipid messengers in the gut. In the present study, we purified the enzyme, identified a part of the amino acid sequence, and found a cDNA in the GenBank TM coding for the protein. The cDNA contains 1841 bp, and the open reading frame encodes 458 amino acids. Transient expression of the cDNA linked to a Myc tag in COS-7 cells increased alk-SMase activity in the cell extract by 689-fold and in the medium by 27-fold. High activity was also identified in the anti-Myc immunoprecipitated proteins and the proteins cross-reacted with anti-human alkSMase. Northern blotting of human intestinal tissues found high levels of alk-SMase mRNA in the intestine and liver. The amino acid sequence shared no similarity with acid and neutral SMases but was related to the ecto-nucleotide phosphodiesterase (NPP) family with 30 -36% identity to human NPPs. Alk-SMase has a predicted signal peptide domain at the N terminus and a signal anchor domain at the C terminus. The ion-binding sites and the catalytic residue of NPPs were conserved, but the substrate specificity domain was modified. Alk-SMase had no detectable nucleotidase activity, but its activity against sphingomyelin could be inhibited by orthovanadate, imidazole, and ATP. In contrast to NPPs, alk-SMase activity was not stimulated by divalent metal ions but inhibited by Zn 2؉ . Differing from NPP2, the alk-SMase cleaved phosphocholine but not choline from lysophosphatidylcholine. Phylogenetic tree indicated that the enzyme is a new branch derived from the NPP family. Two cDNA sequences of mouse and rat that shared 83% identity to human alk-SMase were identified in the GenBank TM . In conclusion, we identified the amino acid and cDNA sequences of human intestinal alk-SMase, and found that it is a novel ectoenzyme related to the NPP family with specific features essential for its SMase activity. Sphingomyelin (SM)1 is a component of all mammalian cell membranes particularly the plasma membrane and the lysosomal membrane. SM is also a dietary component and is mainly present in milk, eggs, meat, and marine products (1, 2). Hydrolysis of SM generates ceramide, sphingosine, and sphingosine 1-phosphate that have regulatory effects on numerous cellular functions such as proliferation, differentiation, and apoptosis (3, 4). At least five types of sphingomyelinase (SMase) have been identified, of which acid and neutral SMases have been cloned (5-9). An enzyme that catalyzes hydrolysis of SM with optimal alkaline pH was first identified in the intestinal content of human and intestinal mucosa of rat and pig by Nilsson (10) and was named alkaline SMase (alkSMase) thereafter (11). Previous studies indicated that alkSMase may be responsible for digestion of dietary SM and for hydrolysis of endogenous SM derived from bile and from the brush borders of sloughed mucosal cells.SM metabolism in the intestine may have implications in colon cancer development. Dietary supplement with SM and ceramide analogues...

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“…Choline is actively secreted into mammalian milk (Noble, 1981;Zeisel et al 1986;Kaufmann & Hagemeister, 1987;Rohlfs et al 1993). The major choline-containing compounds in human, bovine, and rat milk are non-esterified choline, PtdCho, and sphingomyelin (Rohlfs et al 1993).…”

Section: Choline In Milkmentioning

confidence: 99%

Comparative mammalian choline metabolism with emphasis on the high-yielding dairy cow

2002

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The present review examines the importance of choline in dairy cow nutrition. Choline is an essential nutrient for mammals when excess methionine and folate are not available in the diet. The requirement for choline can be met by dietary choline and by transmethylation reactions. Two types of functions for choline are known: functions of choline per se; functions as a methyl donor. The two principal methyl donors in animal metabolism are betaine, a metabolite of choline, and S-adenosyl-methionine, a metabolite of methionine. Choline and methionine are interchangeable with regard to their methyl group-furnishing functions. In adult ruminants, choline is extensively degraded in the rumen; for this reason dietary choline contributes insignificantly to the choline body pool and methyl group metabolism is generally conservative with a relatively low rate of methyl catabolism and an elevated rate of de novo synthesis of methyl groups via the tetrahydrofolate system. In dairy ruminants, the dietary availability of choline is still low, but the output of methylated compounds in milk is high, and precursors from the tetrahydrofolate pathway are limiting, especially at the onset of lactation. Therefore choline may be a limiting nutrient for milk production in high-yielding dairy cows.

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Choline, Phosphatidylcholine and Sphingomyelin in Human and Bovine Milk and Infant Formulas

Cited by 183 publications

References 30 publications

Alkaline sphingomyelinase activity is decreased in human colorectal carcinoma

Alkaline sphingomyelinase activity is decreased in human colorectal carcinoma

Identification of Human Intestinal Alkaline Sphingomyelinase as a Novel Ecto-enzyme Related to the Nucleotide Phosphodiesterase Family

Comparative mammalian choline metabolism with emphasis on the high-yielding dairy cow

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