Vitamin C Deficiency Has Major Impact on Collagen Production
Vitamin C is required to make a protein called collagen which is the major component of connective tissues. The lack of Vitamin C is a deficiency disease called Scurvy.
Why is Collagen Important ?
Collagen is the most abundant protein in the body. It is the structural protein used to make connective tissues, bones, teeth, hair, and arteries. Strong collagen is important for a strong body.
Above Left image: “Unraveling Collagen“, Stainless Steel, height: 11 feet Julian Voss-Andreae, Orange Memorial Park Sculpture Garden, City of South San Francisco, CA. 5/10/2006. Courtesy of Wikimedia Commons
Vitamin C Deficiency Results in Absent Lysine Crosslinking on Collagen
Vitamin C is required for strong collagen. How does this work? Vitamin C is required for lysyl hydroxylase, an enzyme responsible for attaching the lysine residues together on adjacent collagen strands. (see diagram below) Vitamin C deficiency results in weakened collagen strands caused by disrupted lysine crosslinking. The resulting weakened collagen results in a widespread problems in the connective tissues, bones, teeth, skin, hair, arteries, etc.
Steps in Collagen Synthesis (see diagram below Courtesy of Wikimedia)
How are the fibrils crosslinked? This is done with Lysine residues (see below diagram)
Fibril Cross Linking with Lysine and Lysyl Oxydase (see diagram below):
Left Above image courtesy of wikimedia commons lysyl oxidase.
Above image shows three steps in attachment of two fibrils (collagen strands) by combining two lysine molecules with the help of an enzyme lysine hydroxylase which requires vitamin C.
Full Blown Scurvy – Collagen Falls Apart
In the full blown Vitamin C deficiency disease called Scurvy, the structural elements of the body literally fall apart. Collagen is broken down and not replaced. The joints wear out, the small arteries begin to crack and degenerate, the skin shows easy bruising and bleeding as small vessels rupture throughout the body, and the teeth may loosen and fall out.
Linus Pauling: Heart Disease is a Chronic Scurvy Condition
Linus Pauling was unquestionably the greatest scientist of the twentieth century. All of modern biochemistry and molecular biology chemistry is based on Linus Pauling’s work, especially his discovery and elucidation of the chemical bond. Pauling is the only scientist to be awarded two unshared Nobel prizes.
Pauling’s later years were devoted to heart disease, and in 1989 he published “A Unified Theory of Human Cardiovascular Disease,” in which he states that atherosclerotic plaques in heart disease are actually part of a repair process, to repair the arterial damage caused by chronic vitamin C deficiency.
Left Image: Linus Pauling Courtesy of Wikimedia
In essence, Pauling said that heart disease is a manifestation of chronic scurvy, and atherosclerotic plaque is a mechanism evolved to repair or patch blood vessels and arteries damaged by chronic vitamin C deficiency. Linus Pauling also said that atherosclerotic plaque formation can be prevented or reversed with vitamin C, lysine and proline. These are nutritional supplements available at any health food store for a few dollars.
Atherosclerotic Plaques Contain LipoProtein (a)
Plaque deposits found in human aortas are made up of a form of cholesterol called lipoprotein (a) also called Lp(a).
Atherosclerotic Plaques Are Found at Maximal Mechanical Stress
Atherosclerotic plaques are not found randomly distributed throughout the arterial tree, rather distribution is restricted to sites of high mechanical stress such as bifurcations, and areas of motion such as the surface of the heart (coronary arteries). In the early 1950’s, a Canadian, G. C. Willis, MD, made these same observations, and they have been confirmed by 60 years of coronary and peripheral arteriography at major medical centers.
Exposed Lysine Crosslinks from Damaged Collagen is Site of LipoProtein (a) attachment and Plaque Formation
Imagine stepping on your garden hose a thousand times a day. You will soon notice cracks in the wall of the garden hose. This is the same process that happens in the artery. As these cracks open up, the collagen strands in the wall of the artery are teased apart. The triple helix collagen strands are normally bound together with lysine crosslinks which are now teased apart and exposed to the circulating blood stream.
left Image: Lysine courtesy of WIkimedia
The Lysine residues look like little flags waving from the damaged collagen strand. The exposed Lysine strands are available for binding to circulating Lipoprotein (a), a special form of cholesterol that has lysine receptors, and is known to increase heart disease risk. This attachment of lipoprotein(a) to the free lysine residues of damaged collagen initiates the atherosclerotic process. Over time, this process builds larger plaque deposits which eventually narrow the inner diameter of the artery causing a blockage, or leads to plaque rupture and thrombosis, a catastrophic event which may cause heart attack or sudden death.
Animal experiments in genetically modified mice which have “knocked out” the lysine binding sites on lipoprotein (a) show a fivefold reduction in atherosclerotic plaque formation.
Can You Make Vitamin C ? No You Can’t
We humans cannot make vitamin C in our liver as all other animals do. We humans had a genetic mutation in our ancestry 50 million years ago which “knocked out” the final enzyme in the hepatic synthesis of vitamin C. The missing enzyme is called GLO (gulano lactone oxidase). Primates such as gorillas, chimpanzees and orangutans also share this same GLO mutation and cannot make vitamin C. In adddition all primates share with humans susceptibility to heart disease.
Above Image Vitamin C, a simple ring structure simikar to glucose, Ascorbate Courtesy of Wikimedia
All Animals Can Make Vitamin C, but the Guinea Pig Can’t
Except for humans and primates, all other animals have the three enzymes in the liver which can synthesize vitamin C from glucose (a simple sugar). One major exception is the guinea pig, which is really a rodent and not a pig, The guinea pig, for some unexplained reason, shares with humans the identical GLO genetic mutation and also lacks the GLO enzyme just like we do. This makes the guinea pig an ideal experimental model for human diseases. By the way, although animals that make vitamin C never get heart disease, the guinea pig which lacks the ability to synthesize vitamin C, also gets heart disease.
Animals That Make Vitamin C, Don’t Get Atherosclerotic Heart Disease
I though this was worth repeating.
(note: here I am referring to atherosclerotic vascular heart disease in animals. Dogs and Cats DO succumb to other common types of heart disease such as cardiomyopathy and heart worm etc.)
Animals That Don’t Make Vitamin C, Do Get Atherosclerotic Heart Disease
This should be starting to become clear now.
Animal Scientific Support for the Pauling Unified Theory
As mentioned above, guinea pigs are especially well suited to study atherosclerosis because guinea pigs are unable to make their own vitamin C, and in addition, they develop atherosclerotic plaques similar to those found in humans.
Left Image Guinea Pig Courtesy of Wikimedia
G. C. Willis, a Canadian doctor, conducted research with guinea pigs in the 1950’s showing that guinea pigs deprived of dietary vitamin C developed atherosclerotic plaques, while guinea pigs given plentiful vitamin C were protected. In addition,guinea pigs fed a vitamin C deficient diet had elevated Lipoprotein (a) levels along with the increased atherosclerotic plaque formation in the arteries.(link)(link)
Similar findings were demonstrated in genetically engineered mice lacking the GLO enzyme. The GLO deficient mice fed a vitamin C deficient diet developed atherosclerotic plaques in the aorta with characteristic deranged collagen crosslinking. GLO deficient mice fed vitamin C were protected. (link)