16
Sugar T r a n s p o r t Systems and of
the
Evolution
Mutarotases
Downloaded by UNIV LAVAL on October 29, 2015 | http://pubs.acs.org Publication Date: June 1, 1973 | doi: 10.1021/ba-1971-0117.ch016
J. MARTYN BAILEY, PETER G. PENTCHEV, PETER H. FISHMAN, SALLY A. MULHERN, and JOHN W. KUSIAK Biochemistry Department, George Washington University School of Medicine, Washington, D. C. 20005 Diverse transport mechanisms for sugars have evolved in living organisms, including the phosphotransferase and permease systems in bacteria. In mammals several different sugar transport processes seem to have evolved to satisfy the more complex requirements for control and regulation in multicellular organisms. The enzyme mutarotase is found in all tissues which transport glucose, and the embryological and evolutionary development of sugar transport mechanisms in organs of different species correlates well with tissue levels of the enzyme. The inhibition pattern of transport and mutarotase by phloretin and a series of estrogenic compounds are essentially identical. The evidence suggests that the enzyme mutarotase contains some glucose-binding function particularly suitable, which led to its retention through a long evolutionary history in recognizable form in various transport systems for glucose. ' " p h i s review outlines the current knowledge of the enzyme mutarotase (aldose-l-epimerase) and evaluates the evidence that it may have evolved from an origin in primitive bacteria into an important transport system for sugars in higher organisms. It is assumed that transport processes for sugars arose early in the evolution of living systems since synthesis of simple sugars by the formol condensation mechanism would occur at an early stage on the primtive earth. A t the level of the unicellular organism, development of transport systems for nutrients present in the environment would give competitive advantages when the supply became limited. It is presumed that devel opment of specific and efficient transport mechanisms has been under 264 In Carbohydrates in Solution; Isbell, H.; Advances in Chemistry; American Chemical Society: Washington, DC, 1973.
Downloaded by UNIV LAVAL on October 29, 2015 | http://pubs.acs.org Publication Date: June 1, 1973 | doi: 10.1021/ba-1971-0117.ch016
16.
BAILEY E T A L .
Sugar Transport Systems
265
considerable selective pressure and that different mechanisms for solving the problem most efficiently may have evolved in response to different environmental conditions. A brief description of sugar transport i n bacteria and mammals is given principally to illustrate general principles and to outline the diver sity of the processes which have evolved, particularly in mammals. The selection of material for this section is of necessity, therefore, somewhat arbitrary, and more comprehensive surveys of sugar transport may be found in several recent reviews (1, 2, 3, 4, 5, 6, 7, 8, 9,10,11,12,13,14). The evolutionary history and properties of mutarotase is mainly studied here. The enzyme catalyzes the interconversion of the anomeric forms of a number of aldopyranose sugars related configurationally to D-glucose. The specificity and the mechanism of the enzyme catalysis are of considerable basic interest to understanding the mechanism of the mutarotation of sugars. The study of the enzyme also has significance however since it has many of the biological properties attributed to the sugar carrier or permease molecule thought to be involved in active transport of sugars. Since no biological requirement for a catalyst of mutarotation of sugars has been established in higher organisms, there is a distinct possibility that the catalysis of mutarotation is a coincidental consequence of the sugar-binding function of the protein (15, 16). The biological and catalytic properties of mutarotase, therefore, are a subject of considerable theoretical interest for carbohydrate chemistry and for biological transport. Sugar Transport
in Bacteria
Transport processes are often classified into two types: active trans port in which the transported species is transferred across a membrane from a region of lower, to one of higher concentration (i.e., against a thermodynamic potential gradient), and passive transport in which the compound does not accumulate against a concentration gradient but, nevertheless, crosses the membrane at a rate greater than expected by simple diffusion. This latter process is often termed facilitated diffusion. It is generally believed that the active transport process involves at least two subsystems: 1. a component in the membrance capable of combining with the substrate and accomplishing its translocation and 2. a system for coupling the translocation process to a source of energy to establish a concentration gradient. If the energy-coupling mechanism is inactive or blocked, the system then may show the characteristics of passive transport, facilitating transport without the establishment of a concen tration gradient. One of the central outstanding questions i n the study of membrane transport is the exact mechanism of the energy-coupling process.
In Carbohydrates in Solution; Isbell, H.; Advances in Chemistry; American Chemical Society: Washington, DC, 1973.
Downloaded by UNIV LAVAL on October 29, 2015 | http://pubs.acs.org Publication Date: June 1, 1973 | doi: 10.1021/ba-1971-0117.ch016
266
CARBOHYDRATES IN SOLUTION
It seems that i n bacteria at least two different types of active sugar transport have evolved. I n the first of these the phosphotransferase sys tem discovered b y Kundig, Ghosh, and Roseman (17, 18, 19) the sugar undergoes a covalent transformation to the sugar phosphate as an inter mediate stage i n the transport process. In the second type of transport the so called permease system, no covalent transformation of the sugar is apparently necessary (20, 21, 22, 23, 24). For the phosphotransferase system there is no problem i n identifying the energy source for the establishment of the thermodynamic potential gradient. It is apparent that a high-energy phosphate bond i n phosphoenol-pyruvate is the immediate source of the energy responsible for the vectorial translocation of the sugar molecule across the membrane (17). F o r the permease-type systems, however, since no covalent inter mediate has been identified, the source of energy and the type of coupling to the process of translocation have not been defined. The bulk of the evidence favors a coupling of translocation to hydrolysis of high-energy phosphate or to redox processes of the cell (2). Current opinion favors the idea that energy-coupling is mediated via some conformational trans formation of the transport proteins which accomplishes the vectorial translocation. A useful in vitro criterion for identifying the transport protein might be such a conformational change i n response to some type of concentration gradient. Some evidence that the mutarotase protein undergoes such a transformation i n response to osmotic gradients, a transformation which can be reversed by substrate sugars, is presented below. The molecular and enzymatic basis of the permease and phospho transferase types of transport has been under extensive study for several years. The main features of both and the present state of our knowledge concerning the molecular components are outlined schematically i n Figures 1 and 2. H.PR
+
SUGAR
P-ENOLPYR.
+
SU6AR-P
P-H.PR
ENZYME I
ENZYME
PHOSPHOHYDROLASE
II
P-H.PR
SU6AR-P
SUGAR
VECTORIAL PHOSPHORYLATION BY MEMBRANE-BOUND ENZYME
II
RESULTS IN TRANSLOCATION OF SUGAR ACROSS MEMBRANE.
Figure
1. The bacterial phosphotransferase sugar transport system
In Carbohydrates in Solution; Isbell, H.; Advances in Chemistry; American Chemical Society: Washington, DC, 1973.
16.
BAILEY E T A L .
267
Sugar Transport Systems
MEMBRANE.
A
TG
->
T
TG
*TG
IV.
/
T
->TG
T
TG
III.
TG
