Tetrahydrofolic acid structure

Tetrahydrofolic acid then functions as a carrier of one-carbon groups for amino acid and nucleotide metabolism. The basic ring system is able to transfer methyl, methylene, methenyl, or formyl groups, and it utilizes slightly different reagents as appropriate. These are shown here for convenience, we have left out the benzoic acid-glutamic acid portion of the structure. These compounds are all interrelated, but we are not going to delve any deeper into the actual biochemical relationships. 

To date, over 10 000 structural analogues of sulphanilamide, the parent of all sulpha drugs, have been synthesized and used in the SAR studies. However, only about 40 of them have ever been used as prescribed drugs. Sulpha drugs are bactereostatic, i.e. they inhibit bacterial growth but do not actively kill bacteria. These drugs act on the biosynthetic pathway of tetrahydrofolic acid, inhibit dihydropteroate synthetase and mimic the shape of PABA (para-aminobenzoic acid). 

The active form of folic acid, tetrahydrofolic acid (THF), is produced from folate by dihydrofolate reductase in a two-step reaction requiring two moles of NADPH. The carbon unit carried by THF is bound to nitrogen N5 or N10, or to both N5 and N10. THF allows one-carbon compounds to be recognized and manipulated by biosynthetic enzymes. Figure 20.11 shows the structures of the various members of the THF family, and indicates the sources of the one-carbon units and the synthetic reactions in which the specific members participate. 

A metabolic pathway that has received considerable attention is the conversion of 2 -deoxyuridine 5 -monophosphate (dUMP, 6.60) to thymidine 5 -monophosphate (TMP, 6.61) (Scheme 6.13). Without an adequate supply of TMP, a cell or bacterium cannot create DNA for cell division. Therefore, blocking TMP synthesis is an attractive method for slowing the advancement of certain cancers and bacterial infections. Important molecules in the methylation of dUMP are the various folic acid derivatives folic acid (FA, 6.62), dihydrofolic acid (DHF, 6.63), tetrahydrofolic acid (THF, 6.64), and N5, A1 "-methylene tetrahydrofolic acid (MTHF, 6.65) (Figure 6.23). These structures... 

Methotrexate is an antitumor agent whose structure resembles that of folic acid. It inhibits the enzyme that converts folic acid to tetrahydrofolic acid. The inhibition most likely involves which of the following ... 

Methotrexate [meth oh TREX ate] (MTX) is structurally related to folic acid and acts as an antagonist of that vitamin by inhibiting dihydrofolate reductase1, the enzyme that converts folic acid to its active, coenzyme form, tetrahydrofolic acid (FH4) it therefore acts as an antagonist of that vitamin. Folate plays a central role in a variety of metabolic reactions involving the transfer of one-carbon units. (Figure 38.7)2. 

Vitamin M Vitamin M is also called pteroylglutaminic add or folic acid. It was isolated from yeast extract by Wills in 1930. Its structure was described by Anger in 1946. Folic add is made up of pteridine + p-aminobenzoic add + glutamic add. There are several known derivatives, called folates, which are capable of mutual restructuring. The coenzyme tetrahydrofolic acid, which plays a role in many biochemical reactions, is formed with the help of Bi2. Around 50% of total body folate are stored in the liver. A folate-binding protein (FBP) is available for transport. Folate undergoes enterohepatic circulation. The release of folate from the liver cells is stimulated by alcohol, which increases urine excretion. Folate deficiency (e.g. in the case of alcohol abuse) is accompanied by the development of macrocytosis. 

The answer is a. (Murray, pp 627-661. Scriver, pp 3897-3964. Sack, pp 121-138. Wilson, pp 287—320.) The structure shown in the question is the vitamin tolic acid. Tetrahydrofolic acid, the active cofactor derived from lolic acid, is required in two steps of purine synthesis and thus required in the de novo synthesis of ATP and GTE CTP and TTP are pyrimidine base derivatives, and although de novo synthesis of the pyrimidine ring does not require tetrahydrofolate, the formation of thymine from uracil does. NADH and NADPH require niacin for their synthesis. 

Tetrahydrofolic acid. Open-chain analogues of 5,6,7,8-tetrahydrofolic acid were prepared by researchers finm Burroughs Wellcome. None of the ring-opened analogues was as potent as the ring-closed lead structure in inhibiting tumour cell growth. 

Trimethoprim and tetroxoprim inhibit folic acid synthesis, i. e., they specifically inhibit the dihydrofolate reductase which is responsible for synthesis of folic acid. They make possible the reduction of dihydrofolic acid to tetrahydrofolic acid. The structure of purines and pyrimidines is thereby interrupted, an essential step in the synthesis of proteinic and ribonucleic acid. This inhibitory effect is selective and affects bacteria only. 

The structures of the folic acid derivatives and the cyclohydrolase reaction are shown in Fig. 6. Interconversion of these compounds also took place spontaneously at a slow rate (111). AT -Tetrahydrofolic acid was not utilized in transformylation reactions unless it first was converted to an active form (96,108, Hi). 

Figure 1 Structural formula of tetrahydrofolate (THF) compounds. In tetrahydrofolic acid R = H other substituents are listed in Table 1. The asterisk indicates the site of attachment of extra glutamate residues the hatched line and double asterisk indicates the N5 and/or N10 site of attachment of one-carbon units.

Fig. 5. Structure of tetrahydrofolic acid and 2-amino-4-hydroxy-6,7-dimet-hyltetrahydropteridine.

Methotrexate (MTX, chemical structure shown in Fig. 1.) competitively inhibits the dehyrofolate reductase, an enzyme that plays an essential role in purine synthesis. The dehydrofolate reductase regenerates reduced folates when thymidine monophosphate is formed from deoxyuridine monophosphate. Without reduced folates cells are unable to synthesize thymine. Administration of N-5 tetrahydrofolate or N-5 formyl-tetrahydrofolate (folinic acid) can bypass this block and rescue cells from methotrexate activity by serving as antidote. 

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