Ion transport enzymes

J. C. Seou (Aarhus) discovery of the first molecular pump, an ion-transporting enzyme Na+-K+ ATPase. 

The determination of the amino acid sequences of the sarcoplasmic reticulum Ca -ATPase [42] and of the closely related Na, K -ATPase [43,44] have opened a new era in the analysis of ion transport mechanisms. Since 1985, several large families of structurally related ion transport enzymes were discovered [3,34,45-50] that are the products of different genes. Within each family several isoenzymes may be produced from a single gene-product by alternative splicing (Table I). 

John Walker Great Britain discovery of ion transport enzyme Na+, K+ ATPase... 

This discussion clearly demonstrates that drugs do not create functions, but merely stimulate or inhibit functions already inherent in cells. These pharmacodynamic-related interactions occur at various levels of cellular activity, including ion transport, enzymes, coenzymes, nucleic acids, and numerous other biochemical events yet to be delineated. 

Paul D. Boyer (b. 1918 in Provo, Utah) is Professor Emeritus of the University of California at Los Angeles (UCLA). He shared half of the Nobel Prize in Chemistry in 1997 with John Walker (b. 1941), MRC Laboratory of Molecular Biology, Cambridge, England, for their elucidation of the enzymatic mechanism underlying the synthesis of adenosine triphosphate (ATP). [The other half of the 1997 chemistry Nobel Prize went to Professor Jens C. Skou (b. 1918) of Aarhus University, Denmark, for the first discovery of an ion-transporting enzyme, Na , IC-ATPase. ]... 

Skou, Jens C. (1918-). A Danish chemist who won the Nobel Prize in 1997 for his discovery of the first molecular pump, an ion transporting enzyme called Na+-K ATPase. He is emeritus professor of biophysics at Aarhus University, Denmark. He received his Ph.D. from Aarhus University. 

Its cellular functions comprise skeletal and cardiac muscle contraction cellular secretion exocrine, endocrine, and neurotransmitters, neural excitation and regulation of membrane ion transport enzyme regulation (gluconeogenesis and glycogenolysis) and cell growth and division. 

Tlie Na+/K+-ATPase belongs to the P-type ATPases, a family of more than 50 enzymes that also includes the Ca2+-ATPase of the sarcoplasmic reticulum or the gastric H+/K+-ATPase. P-Type ATPases have in common that during ion transport an aspartyl phos-phointermediate is formed by transfer of the y-phosphate group of ATP to the highly conserved sequence DKTGS/T [1]. 

The Na+/K+-ATPase is the only enzyme known to interact with CTS, which reversibly bind to the extracellular side of the Na+/K+-ATPase at the E2-P conformational state [E2-P ouabain] and inhibit ATP hydrolysis and ion transport (Fig. lb, step 4). 

In addition to its effects on enzymes and ion transport, Ca /calmodulin regulates the activity of many structural elements in cells. These include the actin-myosin complex of smooth muscle, which is under (3-adrenergic control, and various microfilament-medi-ated processes in noncontractile cells, including cell motility, cell conformation changes, mitosis, granule release, and endocytosis. 

A well-known example of active transport is the sodium-potassium pump that maintains the imbalance of Na and ions across cytoplasmic membranes. Flere, the movement of ions is coupled to the hydrolysis of ATP to ADP and phosphate by the ATPase enzyme, liberating three Na+ out of the cell and pumping in two K [21-23]. Bacteria, mitochondria, and chloroplasts have a similar ion-driven uptake mechanism, but it works in reverse. Instead of ATP hydrolysis driving ion transport, H gradients across the membranes generate the synthesis of ATP from ADP and phosphate [24-27]. 

Enzymes associated with myelin. Several decades ago it was generally believed that myelin was an inert membrane that did not carry out any biochemical functions. More recently, however, a large number of enzymes have been discovered in myelin [37]. These findings imply that myelin is metabolically active in synthesis, processing and metabolic turnover of some of its own components. Additionally, it may play an active role in ion transport with respect not only to maintenance of its own structure but also to participation in ion buffering near the axon. 

Certain enzymes shown to be present in myelin could be involved in ion transport. Carbonic anhydrase has generally been considered a soluble enzyme and a glial marker but myelin accounts for a large part of the membrane-bound form in brain. This enzyme may play a role in removal of carbonic acid from metabolically active axons. The enzymes 5 -nucleotidase and Na+, K+-ATPase have long been considered specific markers for plasma membranes and are found in myelin at low levels. The 5 -nucleotidase activity may be related to a transport mechanism for adenosine, and Na+, K+-ATPase could well be involved in transport of monovalent cations. The presence of these enzymes suggests that myelin may have an active role in ion transport in and out of the axon. In connection with this hypothesis, it is of interest that the PLP gene family may have evolved from a pore-forming polypeptide [9],... 

In biological systems, therefore, the behavior of Li+ is predicted to be similar to that of Na+ and K+ in some cases, and to that of Mg2+ and Ca2+ in others [12]. Indeed, research has demonstrated numerous systems in which one or more of these cations is normally intrinsically involved, including ion transport pathways and enzyme activities, in which Li+ has mimicked the actions of these cations, sometimes producing inhibitory or stimulatory effects. For example, Li+ can replace Na+ in the ATP-dependent system which controls the transport of Na+ through the endoplasmic reticulum Li+ inhibits the activity of some Mg2+-dependent enzymes in vitro, such as pyruvate kinase and inositol monophosphate phosphatase Li+ affects the activity of some Ca2+-dependent enzymes— it increases the levels of activated Ca2+-ATPase in human erythrocyte membranes ex vivo and inhibits tryptophan hydroxylase. 

---