Apoprotein functions

Catalase (H202 H202 oxidoreductase EC 1.11.1.6) was one of the first enzymes to be isolated in a high state of purity, and its crystallization (29) from beef liver extracts ranked among the early triumphs of biochemistry. Extensive physicochemical studies which followed (30-41) led to an impressive elucidation of its properties, but as yet not to a definition of the apoprotein function in the enzyme catalysis. 

PROBING OF APOPROTEIN FUNCTION IN THE PHOTOSYSTEM II REACTION CENTRE BY PROTEOLYTIC MODIFICATION... 

Probing of Apoprotein Function in the Photosystem II Reaction Centre by Proteolytic... 

Lipoproteins. A lipoprotein is an endogenous macromolecule consisting of an inner apolar core of cholesteryl esters and triglycerides surrounded by a monolayer of phospholipid embedded with cholesterol and apoproteins. The functions of lipoproteins are to transport lipids and to mediate lipid metabolism. There are four main types of lipoproteins (classified based on their flotation rates in salt solutions) chylomicrons, very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). These differ in size, molecular weight, and density and have different lipid, protein, and apoprotein compositions (Table 11). The apoproteins are important determinants in the metabolism of lipoproteins—they serve as ligands for lipoprotein receptors and as mediators in lipoproteins interconversion by enzymes. 

Coenzymes complement the catalytic action of the amino-acid functional groups. They are bound to apoenzymes (apoproteins) either covalently or non-covalently. It is interesting to note that non-covalently-bound coenzymes are polyanions at neutral pH as exemplified by the structures of glutathione (GSH) [17] and thiamine pyrophosphate [18]. Shinkai and Kunitake (1976b, 1977a) demonstrated the efficient binding of glutathione and coenzyme A (a polyphosphate) to cationic micelles and cationic polysoaps. Thus, the combina- ... 

The classes of Upoproteins and the important apoproteins associated with their functions are summarized in Table 1-15-1 and Figure 1-15-4. 

Lipoprotein (a) (abbreviated to Lp(a)) is a complex between LDL and apoprotein (a) that forms spontaneously in blood. Lp(a) is secreted by the liver but its function is unknown. A high plasma level of Lp(a) interferes with the conversion of plasminogen to plasmin, the role of which is to break down blood clots and even disperse small clots. 

Lipoproteins are classified into five groups. In order of decreasing size and increasing density, these are chylomicrons, VLDLs (very-low-density lipoproteins), IDLs (inter-mediate-density lipoproteins), LDLs (low-density lipoproteins), and HDLs (high-density lipoproteins). The proportions of apoproteins range from 1 % in chylomicrons to over 50% in HDLs. These proteins serve less for solubility purposes, but rather function as recognition molecules for the membrane receptors and enzymes that are involved in lipid exchange. 

The answer is D. This patient s tests indicate that he has severe hypercholesterolemia and high blood pressure in conjunction with atherosclerosis. The deaths of several of his family members due to heart disease before age 60 suggest a genetic component, ie, familial hypercholesterolemia. This disease results from mutations that reduce production or interfere with functions of the LDL receptor, which is responsible for uptake of LDL-cholesterol by liver cells. The LDL receptor binds and internalizes LDL-choles-terol, delivers it to early endosomes and then recycles back to the plasma membrane to pick up more ligand. Reduced synthesis of apoproteins needed for LDL assembly would tend to decrease LDL levels in the bloodstream, as would impairment of HMG CoA reductase levels, the rate-limiting step of cholesterol biosynthesis. Reduced uptake of bile salts will also decrease cholesterol levels in the blood. 

Fibronectin (Fn) is ubiquitous throughout the body and serves a number of functions, including coating bacterial and foreign particles with apoprotein which promotes recognition and destruction by circulating cells of the immune system. 

The plasma lipoproteins are spherical macromolecular complexes of lipids and specific proteins (apolipoproteins or apoproteins). The lipoprotein particles include chylomicrons, very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). They differ in lipid and protein composition, size, and density (Figure 18.13). Lipoproteins function both to keep their component lipids soluble as they transport them in the plasma, and also to provide an efficient mechanism for transporting their lipid contents to (and from) the tissues. In humans, the transport system is less perfect than in other animals and, as a result, humans experience a yradual deposition of lipid—especially cholesterol—in tissues. This is a potentially life-threat-en ng occurrence when the lipid deposition contributes to plaque formation, causing the narrowing of blood vessels (atherosclerosis). 

Zinc in metalloenzymes may (i) participate directly in the catalytic process, (ii) serve to stabilize protein structure or (iii) have a regulatory role. In each case, removal of the metal from the holoenzyme generally results in an apoprotein having no catalytic activity. The enzymes considered briefly below provide examples of each of these functions of Zn. The study of zinc metalloproteins has often in the past been beset by analytical problems and by contamination with traces of metal ions a review covering these important topics has appeared.1263 Another recent review deals with the physiological, nutritional and medical role of zinc.1264... 

There are at least nine apoproteins associated with the lipoproteins, as well as several enzymes and a cholesteryl ester transfer protein. There are two major types of apoproteins. Two apoproteins (apo B100 and apo B48) are tightly integrated into the phospholipid monolayer. The other seven proteins are less tightly associated with the phospholipid and exchange among the lipoproteins. The apoproteins have three major functions. (1) They are important structural components. (2) Some of the apoproteins modulate the ac-... 

The structure and function of these apoproteins has been intensely studied in the past decade, and some of the properties of these apoproteins are summarized in table 20.3. All of the apoproteins from human plasma have been sequenced and contain regions that are rich in hydrophobic amino acids, which facilitate binding of lipid. 

Chylomicrons transport dietary triacylglycerol and cholesteryl ester from the intestine to other tissues in the body. Very-low-density lipoprotein functions in a manner similar to the transport of endogenously made lipid from the liver to other tissues. These two types of triacylglycerol-rich particles are initially degraded by the action of lipoprotein lipase, an extracellular enzyme that is most active within the capillaries of adipose tissue, cardiac and skeletal muscle, and the lactating mammary gland. Lipoprotein lipase catalyzes the hydrolysis of triacylglycerols (see fig. 18.3). The enzyme is specifically activated by apoprotein C-II, which... 

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