James C. Osborne

In vitro activation of the enzymic activity of hepatic lipase by apoA‐II

Human post-heparin plasma contains two major lipase activities designated lipoprotein lipase (LPL) and hepatic lipase (HL) [1-3]. LPL is activated by apoC-II [4,5] and aport (/32 glycoprotein I) [6]. Type I hyperlipoproteinemia is associated with a deficiency in the enzymic activity of LPL [7]. A deficiency in apoC-1I also results in type I hyperlipoproteinemia [8] and LPL and apoC-I1 have therefore been proposed to be of major importance in modulating the catabolism of triglyceride-rich lipoproteins in man. The function, natural substrate and regulation of the enzymic activity of ilL have been less well defined. HL activity in human post-heparin plasma is decreased in patients with liver disease and renal failure [9-1 1]. An inverse correlation between HL enzymic activity and the concentration of high density lipoproteins (HDL, d= 1.063-1.21 g/ml [12]) as well as HDL2 (d-1.0631.125 g/ml) has been reported and it has been suggested that HL may play a role in the catabolism of HDL2 [13]. HL enzymic activity has been reported to be inhibited by apolipoproteins C-I, C-II and C-III, and increased by high concentrations of NaC1 and serum [14]. In initial studies we have also observed that human plasma activates HL enzymic activity. It was the purpose of this study to further define the component within plasma which is responsible for this activation. The results of our investigations indicate that under the conditions studied, apoA-II, a protein constituent of human HDL activates HL.

SOLUTION PROPERTIES OF THE PLASMA APOLIPOPROTEINS

The solution properties of apolipoproteins have been investigated extensively by several laboratories over the past few years l-i and reviewed recently.* In the present report we shall summarize briefly the unique molecular properties of these proteins. The intramolecular and intermolecular interactions of apolipoproteins respond dramatically to mild perturbations in their environment and thus an analysis of their structure has yielded valuable insight into the forces responsible for the stability of macromolecules in aqueous solution. It should be stressed that although the molecular properties of apolipoproteins are complex, they are quite reproducible and in many cases predictable. In this review we shall emphasize three major features of the molecular properties of apolipoproteins:

Initial diagnosis of lipoprotein lipase deficiency in a 75-year-old man.

Lipoprotein lipase deficiency, characterized by recurrent pancreatitis, profound hypertriglyceridemia, and delayed clearance of chylomicrons, is generally first diagnosed in childhood. Although patients with this condition have died during episodes of acute pancreatitis in the fourth and fifth decades, no patient older than 50 years has been previously reported. The de novo diagnosis of lipoprotein lipase deficiency in a 75-year-old man illustrates important points about this disease. This inborn error in metabolism may have a relatively benign clinical course resulting in normal life span, particularly if there is strict adherence to a low-fat diet and abstinence from alcohol. Moreover, measurement of lipoprotein lipase activity in persons with severe hypertriglyceridemia and recurrent abdominal pain, even in elderly patients, should lead to the correct diagnosis and treatment of this condition.

Chondronectin: Physical and chemical properties

Chondronectin, the chondrocyte attachment factor, was purified from chicken serum and characterized as to its physical and chemical properties. From sedimentation equilibrium data it was found to have a native molecular weight of 175,800 +/- 800 and a subunit molecular weight of 55,540 +/- 800 in the presence of guanidinium chloride and cysteine, suggesting a trimeric structure linked by disulfide bonds. As visualized by electron microscopy after rotary shadowing, the protein appears compact and globular. The amino acid and carbohydrate compositions of chondronectin are distinct from fibronectin, the fibroblast attachment factor, and laminin, the epithelial cell attachment factor. The activity of chondronectin in promoting attachment of chondrocytes is stable to digestion by collagenase, elastase, and neuraminidase, but is destroyed by trypsin treatment. The data suggest that chondronectin is structurally and chemically distinct from fibronectin and laminin.

Characterization of NAD: Arginine Mono(ADP-Ribosyl)-Transferases in Turkey Erythrocytes: Determinants of Substrate Specificity

Mono(ADP-ribosylation) is catalyzed by transferases identified in viruses, bacteria, and animal cells [1]. Its function has thus far been clearly defined only for certain bacterial toxins that exert their effects on animal tissues by catalyzing the mono(ADP-ribosylation) of critical cellular proteins [1–5]. One of these toxins, choleragen (cholera toxin), an NAD:arginine mono(ADP-ribosyl)transferase, causes the activation of the hormone-sensitive adenylate cyclase from animal tissues by ADP-ribosylating a guanine nucleotide-binding stimulatory protein termed Gs [5]. In vitro, choleragen also catalyzes the ADP-ribosylation of several proteins not related to the cyclase system as well as low molecular weight guanidino compounds, such as the amino acid arginine [6–8]. Animal tissues contain NAD:arginine (ADP-ribosyl)transferases that catalyze reactions similar to those of choleragen [7, 9–11].