Lactose Synthetase

Hill, Robert L.; Brew, Keith

doi:10.1002/9780470122884.ch5

Cited by 75 publications

(35 citation statements)

References 139 publications

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“…α-Lactalbumin (α-LA) is a small acidic Ca 2+ -binding protein involved in the regulation of lactose biosynthesis as a component of lactose synthetase [350,351]. α-LA possesses a single Ca 2+ -binding site and is frequently used as a model Ca 2+ -binding protein distinct from the EFhand family [352,353].…”

Section: Carboxymethylated α-Lactabuminmentioning

confidence: 99%

Amyloidogenesis of Natively Unfolded Proteins

Uversky

2008

CAR

174

152

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Aggregation and subsequent development of protein deposition diseases originate from conformational changes in corresponding amyloidogenic proteins. The accumulated data support the model where protein fibrillogenesis proceeds via the formation of a relatively unfolded amyloidogenic conformation, which shares many structural properties with the pre-molten globule state, a partially folded intermediate first found during the equilibrium and kinetic (un)folding studies of several globular proteins and later described as one of the structural forms of natively unfolded proteins. The flexibility of this structural form is essential for the conformational rearrangements driving the formation of the core cross-beta structure of the amyloid fibril. Obviously, molecular mechanisms describing amyloidogenesis of ordered and natively unfolded proteins are different. For ordered protein to fibrillate, its unique and rigid structure has to be destabilized and partially unfolded. On the other hand, fibrillogenesis of a natively unfolded protein involves the formation of partially folded conformation; i.e., partial folding rather than unfolding. In this review recent findings are surveyed to illustrate some unique features of the natively unfolded proteins amyloidogenesis.

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Section: Carboxymethylated α-Lactabuminmentioning

confidence: 99%

Amyloidogenesis of Natively Unfolded Proteins

Uversky

2008

CAR

174

152

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“…Additionally, in the lactating mammary gland, ␣-lactalbumin converts ␤4GalT-1 to lactose synthase. Interaction of ␤4GalT-1 with this cofactor greatly lowers the K m of the enzyme for glucose, so that glucose can be effectively utilized as acceptor substrate at physiological concentrations (10,11).…”

mentioning

confidence: 99%

Tumor Necrosis Factor-α Up-regulates the Expression of β1,4-Galactosyltransferase I in Primary Human Endothelial Cells by mRNA Stabilization

García-Vallejo

Dijk

Die

et al. 2005

Journal of Biological Chemistry

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During the course of an inflammatory response, the pro-inflammatory cytokine tumor necrosis factor-␣ (TNF␣) triggers endothelial cells to increase the expression levels of adhesion molecules that are pivotal for the rolling, adhesion, and transmigration of leukocytes over the endothelial cell wall. Here we show that TNF␣, in addition, has a regulatory function in the biosynthesis of proper carbohydrate molecules on endothelial cells that constitute ligands for adhesion molecules on leukocytes. Our data show that TNF␣ induced an increase in the expression of ␤1,4-galactosyltransferase-1 (␤4GalT-1) in primary human umbilical vein endothelial cells in a time-and concentration-dependent manner. The ␤4GalT-1 mRNA up-regulation correlated with an increase in the Golgi expression and catalytic activity of the enzyme. Furthermore, an enhanced incorporation of galactose was observed in newly synthesized glycoproteins. Analysis of the molecular mechanism behind the up-regulation of ␤4GalT-1 showed that the increase in mRNA levels is due to an enhanced stability of the transcripts. These data strongly demonstrate that TNF␣ modulates the glycosylation of endothelial cells by a mechanism that directly enhances the stability of ␤4GalT-1 mRNA transcripts.

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“…A complex containing a-lactalbumin and galactosyltransferase catalyzes the final step in lactose biosynthesis. 141 Preclinical studies in animals indicate potential applications of a-lactalbumin in the treatment of epilepsy. Daily administration of a-lactalbumin over a course of 12 days significantly reduced the severity and duration of audible stimulus-induced seizure in genetically susceptible rats and protected against chemically induced seizures in mice.…”

Section: Antiepileptic Properties Of A-lactalbuminmentioning

confidence: 99%

Clinical applications of bioactive milk components

Hill

Newburg

2015

Nutrition Reviews

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Milk represents a unique resource for translational medicine: It contains a rich pool of biologically active molecules with demonstrated clinical benefits. The ongoing characterization of the mechanistic process through which milk components promote development and immunity has revealed numerous milk-derived compounds with potential applications as clinical therapies in infectious and inflammatory disease, cancer, and other conditions. Lactoferrin is an effective antimicrobial and antiviral agent in high-risk patient populations and a potentially potent adjuvant to chemotherapy in lung cancer. Enteric nutrition formulas supplemented with transforming growth factor b, a milk cytokine, have been shown to promote remission in pediatric Crohn's disease. A number of milk glycans, including human milk oligosaccharides, show promise in preclinical studies as antimicrobial and antiinflammatory agents. While active preclinical investigations of human milk may soon result in large-scale production of human milk molecules, bovine milk components in many instances represent a practical source of bioactive milk compounds for use in clinical trials. This review summarizes current efforts to translate the compounds derived from human and bovine milk into effective clinical therapies. These efforts suggest a common pathway for the translation of milk-derived compounds into clinical applications.

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Lactose Synthetase

Cited by 75 publications

References 139 publications

Amyloidogenesis of Natively Unfolded Proteins

Amyloidogenesis of Natively Unfolded Proteins

Tumor Necrosis Factor-α Up-regulates the Expression of β1,4-Galactosyltransferase I in Primary Human Endothelial Cells by mRNA Stabilization

Clinical applications of bioactive milk components

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