Anti-Metabolites and Anti-Vitamins Overview

Anti-Metabolites

• Anti-metabolites are chemicals that inhibit specific metabolic processes. They act by inhibiting the action of a metabolite involved in the normal process.
• Anti-metabolites typically have similar structures to the chemicals they inhibit, but they do not react in the same way.

Anti-Vitamins

• Some anti-vitamins are structural analogues of vitamins, blocking their actions.
• Their action is a form of competitive inhibition and is reversible.
• Some compete with vitamins in specific metabolic processes.
• Others react with vitamins, making them unavailable.
• Anti-vitamins can affect nutrition by replacing and destroying vitamin availability, resulting in vitamin deficiency.
• Anti-vitamins are used in disease control by denying vitamins to disease-causing agents, such as bacteria, while ensuring human processes are not affected.

Examples of Anti-vitamins

Anti-Thiamin

• Pyrithiamin: Replaces the sulfur in thiamin with a vinylene group. Competes with thiamin due to similar structure; strongly antagonistic in humans and animals.
• Oxythiamin: Replaces the amino group with a hydroxyl group, creating an active thiamin antagonist, causing thiamin deficiency in mice.
• Thiaminase: An enzyme that hydrolyzes thiamin. Found in some fresh fish (e.g., carp) and plants (e.g., ferns); mostly heat-sensitive.

Anti-Riboflavin

• No naturally occurring anti-riboflavin substances are currently known.
• Synthetic anti-riboflavin substances have been discovered and show potency in both bacteria and animals.
  • D-araboflavine: Formed by inverting the hydroxyl group on the ribose at position 3. An antagonist in rats.
  • Iso-riboflavine: Formed by shifting a methyl group from position 6 to 8. Antagonist in animals.
  • Dichlororiboflavine: Formed by replacing methyl groups at positions 6 and 7 with chlorine. A bacteriostatic agent.
  • Galactoflavine: An antagonist of riboflavin in rats, especially when riboflavin intake is low; inhibits growth, reversible by increased riboflavin.

Anti-Folates

• Anti-folate substances antagonize the action of folic acid, directly inhibiting cell division.
• This principle is used to treat cancers.
  • Example: Methotrexate is an anti-cancer agent and an immune suppressant.
  • Pteroyl aspartic acid: Formed by replacing glutamic acid with aspartic acid in the folate structure. Antagonistic in bacteria and chicken, but not in rats.
  • Other examples: Sulfanilamide (anti-bacterial agent), Pyrimethamine (anti-malarial drug), methyl folic acid, 4-aminopterin.

Anti-Niacin

• 3-Acetyl pyridine: Formed by replacing the CONH2 group with an acetyl group. Anti-niacin activity in both bacteria and animals.
• Pyridine-3-sulfonic acid: Formed by replacing the CONH2 group with a sulfonic group, with similar anti-niacin activity to 3-acetyl pyridine.

Anti-Biotin

• Avidin: A naturally occurring biotin antagonist found in raw egg albumin of birds, reptiles, and amphibians. Binds to biotin, making it unavailable for cell metabolism.
• Other antagonists include desthiobiotin and biotin sulphonic acid

Anti-Pyridoxine

• Agaritine: A vitamin B6 antagonist naturally found in some plants and mushrooms. Harmful effects are reduced by heating.
• Des-oxypyridoxine: Formed by replacing -CH2OH at position 4 with a methyl group. Antagonistic in mice, chicken, and monkeys.
• Methoxypyridoxine: Formed by replacing the OH group at position 4 with a –OCH3 group. Found in seeds of Ginkgo biloba; a neurotoxin.

Anti-Vitamin K

• Reduces vitamin K action, decreasing blood clotting.
• Used as a poison for small animals (e.g., rats) and as an anticoagulant (blood thinner), such as coumadins (e.g. Warfarin), which is used in the treatment of thrombosis.

Reading Assignment

• Explain why sulfanilamides act as folic acid antagonists in bacteria but not in humans.