Hypothesis: lipoprotein(a) is a surrogate for ascorbate.

Abstract

The concept that lipoprotein (a) [Lp(a)] is a surrogate for ascorbate is suggested by the fact that this lipoprotein is found generally in the blood of primates and the guinea pig, which have lost the ability to synthesize ascorbate, but only rarely in the blood of other animals. Properties of Lp(a) that are shared with ascorbate, in accordance with this hypothesis, are the acceleration of wopnd healing and other cell-repair mechanisms, the strengthening of the extracellular matrix (e.g., in blood vessels), and the prevention of lipid peroxidation. High plasma Lp(a) is associated with coronary heart disease and other forms ofatherosclerosis in humans, and the incidence of cardiovascular disease is decreased by elevated ascorbate. Similar observations have been made in cancer and diabetes. We have formulated the hypothesis that Lp(a) is a surrogate for ascorbate in humans and other species and have marshaled the evidence bearing on this hypothesis.Lipoproteins consist of particles, each of which is a globule of lipid molecules surrounded by an apoprotein shell. Lipoprotein(a) [Lp(a)] was discovered by Blumberg et al. (1) and by Berg (2). It shares with low density lipoprotein (LDL) its lipid and apoprotein composition-mainly apoprotein B-100 (apo B), consisting of a polypeptide chain of 4536 amino acid residues. The unique feature of Lp(a) is an additional glycoprotein, designated apoprotein(a) [apo(a)], which is linked to apo B by disulfide groups. The cDNA sequence of apo(a) (3) shows a striking homology to plasminogen, with multiple repeats of kringle 4, one kringle 5, and a protease domain. The isoforms of apo(a) vary in the range of 300 to 800 kDa and differ mainly in their genetically determined number of kringle 4 structures (3); apo(a) has no plasmin-like protease activity (4), but a serine protease activity has been demonstrated recently (5). Like plasminogen, Lp(a) has been shown to bind to lysine-Sepharose, immobilized fibrin and fibrinogen (6), and the plasminogen receptor on endothelial cells (7)(8)(9). This binding is inhibited by E-aminocaproic acid, certain other amines, and plasminogen.

Lipoprotein(a) and vitamin C impair development of breast cancer tumors in Lp(a)+; Gulo−/− mice

“…Particularly compelling is the fact that the appearance of Lp(a) about 40 million years ago coincided with the loss of endogenous vitamin C synthesis by the ancestor of man. Based on this and other observations it has been proposed that Lp(a) functions as a substitute for vitamin C in stabilizing the ECM, particularly at times of prolonged nutritional scarcity (13). If this concept is confirmed, any pathological condition related to vitamin C deficiency would involve Lp(a) as compensating factor.…”

Connective tissue: Vascular and hematological (blood) support

“…Furthermore, studies have documented NAC's ability to lower homocysteine and lipoprotein (a). (1,44,45) In animal studies, a disturbance in the metabolism of either of these 2 methyl-donor pathways, due to limited availability of either choline, or folates and vitamin B12, has a direct impact on reducing the levels of nutrients in the coexisting pathway since now more of a drain will be placed on the other pathway as a source of methyl groups. For example, rats fed diets deficient in choline and methionine have hepatic folate concentrations half that of controls after 5 weeks.…”

Animal Models as Tools for Translational Research: Focus on Atherosclerosis, Metabolic Syndrome and Type-II Diabetes Mellitus

“…High plasma level of lipoprotein (a) (also called Lp(a)) is associated with coronary heart disease and other forms of atherosclerosis in humans (see review [97]), and as primates, hedgehogs [98] and guinea pigs possess Lp(a) among normal animal models [99]. Guinea pigs are practical model to study the role of oxidized LDL (oxLDL) in progression of atherosclerosis [100].…”