Lactose synthase

O Keefe, E.T., Mordick, T., and Bell, J.E. (1980) Bovine galactosyltransferase Interaction with a-lactalbu-min and the role of a-lactalbumin in lactose synthase. Biochemistry 19, 4962-4966. 

LACTOSE SYNTHASE LACTOSE SYNTHASE Lactosylceramide a-2,6-N-sialyltransferase, SIALYLTRANSFERASE Lag phase in microtubule assembly, MICROTUBULE ASSEMBLY KINETICS Lag phase in polymerization,... 

How is lactose made in mothers milk What is unusual about the subunit structure of lactose synthase ... 

Tsuruta O, Shinohara G, Yuasa H et al (1997) UDP-N-acetyl-5-thio-galactosamine is a substrate of lactose synthase. Bioorg Med Chem Lett 7 2523-2526... 

Ramakrishnan, B. and Qasba, P.K. 2001. Crystal structure of lactose synthase reveals a large conformational change in its catalytic component, the beta-1,4-galactosyltransferase-I. JMol Biol 310(1) 205—218. 

In some instances, the specificity of an enzyme may be altered by its association with a modifier subunit. An example is lactose synthase, the enzyme that catalyzes the linking of glucose and galactose to form lactose. This enzyme consists of a catalytic subunit and a modifier subunit. By itself, the catalytic subunit catalyzes the addition of a galactose residue to a carbohydrate chain of a glycoprotein in the presence of the modifier (a-lactalbumin) the specificity is changed and lactose is synthesized. 

Recently, the molten globule state of a-lactalbumin has been shown to possess antitumor activity when complexed with a fatty acid [36,37], and hence the protein may possess secondary biological activity in addition to the primary activity of native a-lactalbumin, i.e., substrate specificity modifier activity in a lactose synthase system [38,39]. The molten globule of a-lactalbumin thus provides an example of the folding intermediate of a protein exhibiting a secondary biological activity. 

There have been previous reviews on a-lactalbumin and lysozyme, especially during 1970—1975. The reviews on lysozyme include the conference proceedings edited by Osserman et al. (1974) and the reviews by Imoto et al. (1972), Jolles and Jolles (1984), and Proctor and Cunningham (1988). Work on a-lactalbumin and lactose synthase has been reviewed by Brew (1970), Hill and Brew (1975), Brew and Hill (1975), and Hall and Campbell (1986). 

We open with a brief report of the early discovery of the occurrence and isolation of these proteins and the elucidation of their function and homology, followed by a brief discussion of some problems in their isolation and the determination of their activity. We then consider various aspects of their three-dimensional structures and their significance. We summarize studies on the implications of their sequence similarities, and also on the binding of metal ions, especially calcium(H), and consider their implications. Then follows a brief discussion of lactose synthase, an enzyme of which a-lactalbumin and galactosyltransferase are essential components. We then examine the evidence concerning the evolution of the two proteins, about which there are conflicting views (see Section X,B). Some conclusions and predictions of future directions are made. 

The substrate specificity of the lactose synthase system was studied further by Brew et al. (1968). They confirmed that neither A protein nor B protein alone was active for the synthesis of lactose, but the A protein catalyzed the following reaction (see also Eig. 2) ... 

Fig. 2. Reactions catalyzed by galactosyltransferase (GT). (a) The incorporation of galactose (Gal) into a (1—>4) linkage with JV-acelylglucosamine (NAG) to form N-acetyl-lactosamine (NAL). UDP, Uridine diphosphate, (b) Modification of the activity of GT by a-lactalbumin (a-LA) to convert it to a lactose synthase catalyzing the formation of lactose from UDP-Gal and glucose.

While known sequencing methods may enable the sequence or partial sequence to be established for an impure protein [e.g., cow milk lysozyme (White et al., 1988)], protein of high purity is required for other purposes (e.g., determination of trace lytic activity in an isolated a-lactalbumin or trace lactose synthase specifier activity in a lysozyme). Otherwise, erroneous conclusions may be drawn with respect to structure and function and their evolutionary relationships. 

A necessary, but insufficient, property for a protein to be an a-lactalbumin is its ability to act as a specifier in the lactose synthase system. There is, at present, controversy as to whether a true a-lactalbumin occurs in the milk of monotremes. Thus, it is essential to have good methods for the determination of galactosyltransferase and lactose synthase activities. They must enable the detection of low levels of activity. This is... 

Hopper and McKenzie (1974), in their study of the possible ability of echidna lysozyme to act as specifier protein for the production of weak lactose synthase activity, found that the conditions of the determination needed modification for these purposes. A preliminary study was made by H. A. McKenzie and V. Muller (unpublished observations) of optimum conditions for such determinations. However, it was evident that much further work was necessary. The effect of lipids on gtdactosyl-transferase activity has been studied by Mitranic and Moscarello (1980). 

D. Structural Changes on Cation Binding by a-Lactalbumin and Their Implications in Lactose Synthase Activity... 

---