Biochemistry - The Chemical Reactions of Living Cells Volume 2 - D. Metzler 1980

Types of reactions catalyzed by enzymes
Coenzymes - specific natural specialized reagents

Most of the reactions discussed in Chapter 7 are catalyzed by Enzymes containing only functional groups located in amino acid side chains. Coenzymes frequently act as additional Reagents required for reactions that would be hindered or impossible if enzyme action relied solely on simple Acid-Base Catalysis. In many cases, coenzymes also serve as carriers—catalysts that alternately accept and donate chemical groups, hydrogen atoms, or electrons.

Coenzymes can be divided into three groups:

1. Compounds with a high group-transfer potential, such as ATP and GTP, which participate in cellular energy transformation. Because ATP is released from the enzyme complex only after being cleaved, it is more often considered a substrate rather than a coenzyme. However, ATP can also be viewed as a phosphorylated form of AMP or ADP that acts as a carrier of "high-energy" phosphate groups.

2. Compounds that are frequently vitamin derivatives (Supplement 8-A). Located within the Active Site of the enzyme, they interact with the substrate and alter its Structure in a way that enhances its reactivity. Most coenzymes, including coenzyme A (CoA), Pyridoxal phosphate, Thiamine diphosphate, and the Coenzyme forms of vitamin B₁₂, belong to this group.

3. Oxidation-reduction coenzymes containing specific structures with a strictly defined redox potential. Coenzymes in this group function as carriers of hydrogen atoms or electrons, as, for example, NAD⁺, NADP⁺, FAD, and Lipoic Acid.

Some coenzymes, such as NAD⁺ and NADP⁺, readily dissociate from Protein Complexes, thereby mediating The transfer of hydrogen atoms from one enzyme to another. At the same time, many coenzymes, such as FAD, are bound much more tightly and are only rarely released from the catalytic protein complex. Heme groups are frequently covalently linked to Proteins, such as cytochrome c, and cannot be detached without disrupting the enzyme. Very tightly bound coenzymes are often referred to as prosthetic groups, although there is no sharp boundary between prosthetic groups and loosely bound coenzymes.

Supplement 8-A

The Discovery of Vitamins

Until the present century, certain mysterious and frequently fatal diseases caused by vitamin deficiencies were widespread. Their victims were often sailors on long voyages. Several centuries ago, perceptive individuals realized that improper Nutrition was the cause of these disorders. In the East, beriberi was rampant—millions of people died from the strange paralyses (polyneuritis) associated with the disease. A Chinese friend of mine told me that for many generations the Chinese knew that a decoction of rice bran cured beriberi, but this knowledge was either not widely disseminated or was met with skepticism.

In 1893, the Dutch physician Christiaan Eijkman, working on the island of Java, experimentally induced paralysis in chickens by feeding them the polished white rice consumed by the local population. Eijkman also demonstrated that the symptoms of paralysis rapidly disappeared when a rice bran extract was added to their feed. Initially, he believed that white rice contained some toxic compound neutralized by a substance present in the bran. Later, he arrived at the correct Conclusion that rice bran contains an essential nutrient.

In 1912, the Polish biochemist Kazimierz Funk formulated the "vitamin theory," according to which beriberi, pellagra, Rickets, and scurvy are caused by the absence of four distinct vital nutrients from the diet. Funk thought that all of them were amines, which is how the word "vitamine" originated. That same year in England, F. G. Hopkins reported that he had maintained rats on a diet of purified foods and discovered that surprisingly small amounts of "accessory growth factors," obtainable from milk, were required for normal growth¹⁾.

By 1915, McCollum and Davis at the University of Wisconsin established that rat growth depends not on one, but on two accessory factors. They named the one soluble in organic Solvents "A" and designated the Water-soluble one as "B." Factor B cured chickens of beriberi. Several years later, when it was shown that vitamin A is not an amine, the final "e" was dropped from the word "vitamine," and the term "vitamin" was adopted to designate these accessory growth factors.

Progress in isolating vitamins was slow, largely due to insufficient interest in them. According to R. R. Williams, at the time he began his work on isolating the anti-beriberi factor (1910), most scientists were convinced that all his efforts were doomed to failure, so deeply entrenched were Pasteur's ideas that diseases are caused solely by Bacteria.

¹⁾ For these discoveries, Funk and Hopkins were awarded the 1929 Nobel Prize in Medicine.

In 1926, Jansen isolated a small amount of thiamine, but it was not until 1933 that Williams, working with virtually no financial support, managed to obtain a relatively large quantity of the crystalline compound from rice bran. Shortly thereafter, its properties were rapidly studied and its chemical synthesis accomplished.

It soon became clear that the new vitamin did not fully satisfy the dietary requirements of rats for Factor B. Furthermore, it turned out that In addition to thiamine (vitamin B₁), which was highly unstable and easily destroyed by heat, another heat-stable factor (vitamin B₂) was also required. A few years later, it became apparent that this other factor also contained more than one compound. This mixture came to be known as the vitamin B₂ complex. Confusion persisted until relatively specific animal assays were developed for each of the components. It was established that while riboflavin is largely responsible for growth stimulation, vitamin B₆ prevents Skin lesions around the snout, or "pellagra," in rats. Pantothenic acid is particularly effective in treating dermatitis in chickens, whereas nicotinamide proved essential for treating pellagra in humans. Biotin is required for Yeast growth.

The substance exhibiting anti-scurvy (antiscorbutic) activity was named Vitamin C, and once its structure became known, ascorbic acid. The fat-soluble factor preventing rickets was designated as vitamin D. By 1922, it was clear that another fat-soluble factor (vitamin E) existed, which is necessary for normal Pregnancy in rats, and in the early 1930s the list of vitamins was augmented by vitamin K and Essential Fatty acids. Investigations into human Blood disorders—tropical macrocytic anemia and pernicious anemia—led to the discovery of two more Water-Soluble Vitamins: Folic Acid and vitamin B₁₂. The latter, required in vanishingly small amounts, was not isolated until 1948.

Have all vitamins been discovered? Most scientists believe so. Rats can be raised on a practically completely synthetic diet. However, there is always the possibility that humans require some yet-undiscovered substances present in our food for optimal health.