Bacteria folic acid requirements

Bacteria require p-aminobenzoic acid to biosyn thesize folic acid a growth factor Structurally sul fanilamide resembles p-aminobenzoic acid and is mistaken for it by the bacteria Folic acid biosynthesis IS inhibited and bacterial growth is slowed suffi ciently to allow the body s natural defenses to effect a cure Because animals do not biosynthesize folic acid but obtain it in their food sulfanilamide halts the growth of bacteria without harm to the host... 

Both sulfonamides and trimethoprim (not a sulfonamide) sequentially interfere with folic acid synthesis by bacteria. Folic acid functions as a coenzyme in the transfer of one-carbon units required for the synthesis of thymidine, purines, and some amino acids and consists of three components a pteridine moiety, PABA, and glutamate (Fig. 44.1). The sulfonamides, as structural analogues, competitively block PABA incorporation sulfonamides inhibit the enzyme dihydropteroate synthase, which is necessary for PABA to be incorporated into dihydropteroic acid, an intermediate compound in the formation of folinic acid. Since the sulfonamides reversibly block the synthesis of folic acid, they are bacteriostatic drugs. Humans cannot synthesize folic acid and must acquire it in the diet thus, the sulfonamides selectively inhibit microbial growth. 

Antifolate not easily assimilated by non-folic-acid-requiring bacteria ... 

In terms of amino acids bacterial protein is similar to fish protein. The yeast s protein is almost identical to soya protein fungal protein is lower than yeast protein. In addition, SCP is deficient in amino acids with a sulphur bridge, such as cystine, cysteine and methionine. SCP as a food may require supplements of cysteine and methionine whereas they have high levels of lysine vitamins and other amino acids. The vitamins of microorganisms are primarily of the B type. Vitamin B12 occurs mostly hi bacteria, whereas algae are usually rich in vitamin A. The most common vitamins in SCP are thiamine, riboflavin, niacin, pyridoxine, pantothenic acid, choline, folic acid, inositol, biotin, B12 and P-aminobenzoic acid. Table 14.4 shows the essential amino acid analysis of SCP compared with several sources of protein. 

Formation of THF from dihydrofolate (DHF) is catalyzed by the enzyme dihydrofolate reductase. DHF is made from folic acid, a vitamin that cannot be synthesized in the body, but must be taken up from exogenous sources. Most bacteria do not have a requirement for folate, because they are capable of synthesizing folate, more precisely DHF, from precursors. Selective interference with bacterial biosynthesis of THF can be achieved with sulfonamides and trimethoprim. 

The formation of sulfa drugs is another excimple of a multistep synthesis. The sulfa drugs cire bactericides, effective c ainst a wide variety of bacteria because they mimic p-aminobenzoic acid (Figure 13-48). Many bacteria require p-aminobenzoic acid, which they cire unable to synthesize, and need to synthesize folic acid. Many types of sulfa drugs exist, and most of them involve the substitution of one of the hydrogen atoms on the -SO2-NH2. Prontosil (Figure 13-49) was the first commercially available sulfa drug. The metabolism of prontosil produced sulfanilamide. 

All of these compounds are inhibitors of dihydrofolate reductase in bacteria, plasmodia, and humans. Fortunately, they have a significantly higher affinity to bacterial and protozoal dihydrofolate reductase. Pyrimethamine, for example, inhibits dihydrofolate reductase in parasites in concentrations that are a several hundred times lower than that required to inhibit dihydrofolate reductase in humans. This is the basis of their selective toxicity. Selective toxicity can be elevated upon the host organism s production of folic acid, which parasites are not able to use. 

About 10-25%, i.e. 50-200 pg, of the daily dietary intake of folic acid in yeasts, liver, and green vegetables is absorbed via active and passive transport in the proximal jejunum. As humans do not have dihydropteroate synthetase, which synthesizes folic acid in bacteria, we require folic acid in the diet. Only small amounts of folate can be stored in the body and dietary deficiency for only a few days can result in symptomatic folate deficiency. 

Mectianism of Action Interferes with synthesis of folic acid that bacteria require for growth by inhibition of para-aminobenzoic acid metabolism. Therapeutic Effect Prevents further bacterial growth. 

Mammalian cells (and some bacteria) lack the enzymes required for folate synthesis from PABA and depend on exogenous sources of folate therefore, they are not susceptible to sulfonamides. Sulfonamide resistance may occur as a result of mutations that (1) cause overproduction of PABA, (2) cause production of a folic acid-synthesizing enzyme that has low affinity for sulfonamides, or (3) impair permeability to the sulfonamide. Dihydropteroate synthase with low sulfonamide affinity is often encoded on a plasmid that is transmissible and can disseminate rapidly and widely. Sulfonamide-resistant dihydropteroate synthase mutants also can emerge under selective pressure. 

Sulfonamides are structural analogs of PABA that competitively inhibit bacterial synthesis of folic acid (see p. 371). Because purine synthesis requires THF as a coenzyme, the sulfa drugs slow down this pathway in bacteria. 

Vitamins and Minerals. Milk is a rich source of vitamins and other organic substances that stimulate microbial growth. Niacin, biotin, and pantothenic acid are required for growth by lactic streptococci (Reiter and Oram 1962). Thus the presence of an ample quantity of B-complex vitamins makes milk an excellent growth medium for these and other lactic acid bacteria. Milk is also a good source of orotic acid, a metabolic precursor of the pyrimidines required for nucleic acid synthesis. Fermentation can either increase or decrease the vitamin content of milk products (Deeth and Tamime 1981 Reddy et al. 1976). The folic acid and vitamin Bi2 content of cultured milk depends on the species and strain of culture used and the incubation conditions (Rao et al. 1984). When mixed cultures are used, excretion of B-complex vita-... 

The antiscurvy (antiscorbutic) activity was called vitamin C, and when its structure became known it was called ascorbic acid. The fat-soluble factor preventing rickets was designated vitamin D. By 1922, it was recognized that another fat-soluble factor, vitamin E, is essential for full-term pregnancy in the rat. In the early 1930s vitamin K and the essential fatty acids were added to the list of fat-soluble vitamins. Study of the human blood disorders "tropical macrocytic anemia" and "pernicious anemia" led to recognition of two more water-soluble vitamins, folic acid and vitamin B12. The latter is required in minute amounts and was not isolated until 1948. Have all the vitamins been discovered Rats can be reared on an almost completely synthetic diet. However, there is the possibility that for good health humans require some as yet undiscovered compounds in our diet. Furthermore, it is quite likely that we receive some essential nutrients that we cannot synthesize from bacteria in our intestinal tracts. An example may be the pyrroloquinoline quinone (PQQ).e... 

Tetrahydrofolate (THF) The active form of the vitamin folic acid. THF is one of the major carriers of one-carbon units at various oxidation states for biosynthetic reactions. It is required for the synthesis of the nucleotide thymidylate (dTMP). Although bacteria can synthesize folic acid, eukaryotes must obtain folate from the diet. Dietary sources of folate include leafy green vegetables (e.g., spinach and turnip greens), citrus fruits, and legumes. Many breakfast cereals, breads, and other grain products are fortified with folate. 

D. Bacteria must synthesize the folate that is required for their biosynthetic processes they do not have a transporter to bring folate into the cell. Trimethoprim inhibits prokaryotic DHFR (eukaryotic is not affected) and sulfamethoxazole is an analog of p-aminobenzoic acid (PABA), a precursor to folic acid. Bacteria will use this analog instead of PABA and produce a nonfunctional folate. 

Folic acid is a vitamin required for the transfer of methyl groups in the biosynthesis of methionine and nitrogenous bases. Humans cannot synthesize folic acid and must obtain it from the diet. Bacteria, on the other hand, must make folic acid because they cannot take it in from the environment. 

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