Anti-Metabolites PDF

1 Introduction  Chemicals that inhibit specific metabolic processes by inhibiting the action (s) of a metabolite involved in the normal process  Anti-metabolites usually have structures similar to the chemicals they inhibit, but do not react in same way...

1 Introduction  Chemicals that inhibit specific metabolic processes by inhibiting the action (s) of a metabolite involved in the normal process  Anti-metabolites usually have structures similar to the chemicals they inhibit, but do not react in same way 2 Anti-vitamins  Some are structural analogues of vitamins and therefore can block the actions of the vitamins  Actions are competitive inhibition and reversible  Some compete with vitamins in specific metabolic processes  Others may react with vitamins and make them unavailable 3 Anti-vitamins  Can affect the nutrition of individual by replacing and destroying vitamin availability  Results in vitamin deficiency  Disease control: introduction results in denying vitamin to disease-causing agents e.g. bacteria  Ensure that human processes are not affected 4 5 1. Anti-thiamin A. Pyrithiamin:  ‘S’ in the thiazole group is replaced with vinylene group (- CH=CH-)  Competes with thiamin because of similar structure  Strongly antagonistic in both humans and animals 6 1. Anti-thiamin B. Oxythiamin:  NH2 group is replaced by OH group at position 4  Results in active thiamin antagonist  Can produce thiamin deficiency in mice 7 1. Anti-thiamin C. Thiaminase:  An enzyme that hydrolyses thiamin  Present especially in some fresh fish e.g. carp, some plants e.g. ferns  Mostly heat-sensitive 8 2. Anti-riboflavin  No naturally-occurring anti-riboflavin substance have been identified yet  Synthetic ones exist which have shown potency in both bacteria and animals 10  2. Anti-riboflavin A. D-araboflavine:  Formed by the inversion of OH group located on the ribose at position 3  Antagonist in rats B. Iso-riboflavine:  Formed by shifting methyl group from position 6 to 8  Antagonist in animals C. Dichlororiboflavine:  Formed by replacing the methyl groups at positions 6 and 7 with Cl-  Bacteriostatic agent 11 2. Anti-riboflavin D. Galactoflavine:  An antagonist of riboflavin in rats, especially when intake of riboflavin is low  Effect: inhibited growth  Reversed by increased intake of riboflavin 12 3. Anti-folate substances  Antagonize the action of folic acid  Directly inhibits cell division  Principle used in the treatment of cancers  E.g. Methotrexate – anti cancer agent, immune suppresant 13 3. Anti-folates A. Pteroyl aspartic acid:  Formed by replacing glutamic acid with aspartic acid in the folate structure  Antagonistic in bacteria and chicken, not in rats B. Some selectively act in microorganisms but not in mammals  Sulfanilamide (anti-bacterial agent)  Pyrimethamine (anti-malarial drug) C. Other anti-folates include methyl folic acid, 4- aminopterin 14 4. Anti-Niacin substances A. 3-Acetyl pyridine:  Formed by replacing CONH2 group with acetyl group  Anti- niacin activity in both bacteria and animals B. Pyridine-3-sulfonic acid:  Formed by replacing CONH2 group with sulphonic group  Similar activity as 3-Acetyl pyridine 15 5. Anti-Biotin A. Avidin:  Naturally occurring biotin antagonist in the raw egg albumin of birds, reptiles and amphibians  A protein that binds to biotin, making it unavailable for cell metabolism  Chicks fed on diet containing uncooked egg white became biotin deficient, although diet had adequate amount of vitamin  Other antagonists are desthiobiotin and biotin sulphonic acid 16 6. Anti-Pyridoxine A. Agaritine:  A vitamin B6 antagonist, naturally in some plants and mushrooms  Harmful effect greatly reduced by heating B. Des-oxypyridoxine:  Formed by replacing –CH2OH at position 4 with methyl group  Antagonistic in mice, chicken and monkeys C. Methoxypyridoxine:  Formed by replacing OH group at position 4 with –OCH3 group  Found in seeds of Ginkgo biloba  Neurotoxin 17 7. Anti-Vitamin K  Reduce vitamin K action and therefore results in decreased blood clotting  Used as poison for small animals e.g. rats, and as an anti-coagulant (blood thinners)  Coumadins e.g. Warfarin for treating thrombosis 18 Reading Assignment  Why do sulfanilamides act as folic acid antagonists in bacteria, but not in humans? 19