Lactose synthetase, lactalbumin

Bovine a-lactalbumin is one of the two enzymes in lactose synthetase, and its amino acid sequence shows striking similarities to that of lysozyme.118 A model based on the lysozyme model has been built, and the side-chain interactions found are convincing, showing that the model is essentially correct. The active cleft in the crystal is, however, shorter than that in the model, and is consistent with a mono- or di-saccharide as the substrate. Thus, the lysozyme structure may serve as a model for some enzymes that synthesize and hydrolyze carbohydrates. 

Denton, W. L. nd Ebner, K. E. 1971. Effect of tyrosyl modification on the activity of a-lactalbumin in the lactose synthetase reaction. J. Biol. Chem. 246, 4053-4059. 

Brew, K. 1969. Secretions of a-lactalbumin into milk and its relevance to the organization and control of lactose synthetase. Nature iLondon) 222, 671-672. 

In protein cross-linking studies, DMP has been used to examine the subunit structure of muscle pyruvate kinase (Davies and Kaplan, 1972), for the cross-linking of lactose synthetase (Brew et al., 1975), and to conjugate a fluorescent derivative of a-lactalbumin to glactosyltransferase (O Keefe et al., 1980). The reagent also has... 

Q -Lactalbumin (a-LA) is a component of mammalian milk. It complexes with jS-galactosyl transferase to form lactose synthetase that catalyzes the synthesis of lactose. Unlike most of the other known calcium-binding proteins that have clusters of calcium ions or cooperative calcium binding, only one calcium-binding site with very high calcium-binding... 

Brodbeck and Ebner found that the soluble lactose synthetase from milk can be separated into two protein components, A and B, which individually do not exhibit any catalytic activity however, their recombination restores full lactose synthetase activity. The B fraction has been crystallized from bovine skim milk and bovine mammary tissue, and was identified as a-lactalbumin. It was thus found that a-lactalbumin can be substituted for the B protein of lactose synthetase. Lactose synthetases from the milk of sheep, goats, pigs, and humans were also resolved into A and B proteins, and the fractions from these species were shown to be qualitatively interchangeable in the rate assay of lactose synthesis. Determination of the amino acid sequence of a-lactalbumin (B fraction) has shown a distinct homology in the sequence of amino acids of a-lactalbumin and hen s egg-white lysozyme, suggesting that lysozyme and a-lactalbumin have evolved from a common ancestral gene. 

K, Brew, T.C. Vanaman and R.L, Hill, The role of a-lactalbumin and the A protein in lactose synthetase a unique mechanism for the control of a biological reaction. Proc. Natl Acad. Sci. USA, 1968, 59, 491-497. 

However, in the lactating mammary gland this enzyme associates with milk protein, a-lactalbumin, forming a complex, denoted lactose synthetase, which instead catalyzes the formation of lactose from glucose and UDP-galactose. 

The components of the lactose synthetase complex are freely dissociable, the a-lactalbumin lowering the apparent Km for glucose and other monosaccharides as compared with the Km observed for the uridyl-transferase alone. The function performed by lactalbumin—of enhancing the substrate binding for a reaction, (with the substrate in this instance being glucose)—is reminiscent of that of metals in certain enzyme systems (Hill and Brew, 1975). Recently, Powell and Brew (1976) have shown that prior attachment of Mn to the enzyme is necessary for its binding of a-lactalbumin. 

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