Folic acid or folate does not occur in nature. 3
Elucidation of the anaerobic pathway for the corrin component of cobalamin (vitamin B12) September 10, 2013
The anaerobic route has remained enigmatic because many of its intermediates have proven technically challenging to isolate, because of their inherent instability. The full step-by-step in vitro synthesis of cobyrinic acid from ALA requires 14 enzymes
Nearly all animal life is dependent on bacteria for survival as only bacteria and some archaea possess the genes and enzymes necessary to synthesize vitamin B12, also known as cobalamin, and provide it through the food chain. 1 Vitamin B12, also known as cobalamin, is a water-soluble vitamin involved in the metabolism of every cell of the human body. It is one of eight B vitamins. It is a cofactor in DNA synthesis, and in both fatty acid and amino acid metabolism. 2
As such, it is life essential, and its origin is a origin of life problem.
Tetrahydrofolate ( THF H4 folate ) and Vitamin B12
One-carbon Metabolism: Basic Concepts
There is a group of biochemical reactions that have a special set of enzymes and coenzymes. They are involved in amino acid metabolism and also play roles in nucleotide metabolism. This group of reactions is referred to as one-carbon metabolism because what they have in common is the transfer of one-carbon groups. One-carbon metabolism exists because one-carbon groups are too volatile and need to be attached to something while being processed. 42 Essentially, there are three ways of moving groups of atoms containing a single carbon atom using the following molecules:
- Tetrahydrofolate (THF) as a cofactor in enzymatic reactions.
- S-adenosylmethionine (SAM) as a methyl (-CH3) donor.
- Vitamin B12 (Cobalamin) as a co-enzyme in methylation and rearrangement reactions.
TETRAHYDROFOLATE (THF) is the most versatile one-carbon donor in biosynthetic reactions. THF is composed of three types of groups. THF is derived from the vitamin folic acid (folate). Folate is made by plants and microorganisms. The enzyme dihydrofolate reductase converts dihydrofolate into tetrahydrofolate, which is the active form that carries 1-carbon groups in a variety of reactions. All organisms require reduced folate cofactors for the synthesis of a variety of metabolites. Most microorganisms must synthesize folate de novo because they lack the active transport system of higher vertebrate cells that allows these organisms to use dietary folates. 38Tetrahydrofolate (H4 folate) has fundamental importance for the biosynthesis of purines, pyrimidines, and several amino acids. The folate derivative, 5,10-methylene-tetrahydrofolate is essential for the synthesis of dTMP from dUMP and it is, therefore, crucial for DNA replication and cell division. Tetrahydrofolate is an essential substrate in the biosynthesis of amino acid, glycine. Dihydrofolate reductase enzyme replenishes tetrahydrofolate from dihydrofolate for the above mentioned biosynthetic processes. 36 Folate is necessary for the production and maintenance of new cells , for DNA synthesis and RNA synthesis through methylation , and for preventing changes to DNA , and, thus, for preventing cancer . It is especially important during periods of frequent cell division and growth, such as infancy and pregnancy. Folate is needed to carry one-carbon groups for methylation reactions and nucleic acid synthesis (the most notable one being thymine, but also purine bases). It gets this carbon atom by sequestering formaldehyde produced in other processes. Thus, folate deficiency hinders DNA synthesis and cell division, affecting hematopoietic cells and neoplasms the most because of their greater frequency of cell division. 37
In the form of a series of tetrahydrofolate (THF) compounds, folate derivatives are substrates in a number of single-carbon-transfer reactions, and also are involved in the synthesis of dTMP (2′-deoxythymidine-5′-phosphate) from dUMP (2′-deoxyuridine-5′-phosphate). It is a substrate for an important reaction that involves vitamin B12 and it is necessary for the synthesis of DNA, and so required for all dividing cells
Tetrahydrofolate THF can be imagined as an arm that transfers single carbons in different reduced states from one molecule to another.
The importance of folate compounds in metabolism has been established for over 50 years. Folate derivatives participate in a myriad of biosynthetic reactions involving transfers of groups containing a single carbon atom. For example, these functional units are essential components in the metabolism of the amino acids glycine, serine, methionine, and histidine, and the biosynthesis of purines and pyrimidines. 21 Tetrahydrofolic acid is a cofactor in many reactions, especially in the synthesis (or anabolism) of amino acids and nucleic acids. It gets this carbon atom by sequestering formaldehyde f produced in other processes. 10 Tetrahydrofolate acts as a donor or acceptor of one-carbon unit in biosynthetic and degradative processes and has an essential role in the biosynthesis of purines, thymidylate, pantothenate, RNA and amino acids, such as methionine and glycine-to-serine conversion 18 There is a group of biochemical reactions that have a special set of enzymes and coenzymes. They are involved in amino acid metabolism and also play roles in nucleotide metabolism. This group of reactions is referred to as one-carbon metabolism because what they have in common is the transfer of one-carbon groups. 11
It means moving a carbon atom from one molecule to another. THF is the most versatile one-carbon donor in biosynthetic reactions. THF is composed of three types of groups. THF is derived from the vitamin folic acid (folate). Folate is made by plants and microorganisms. The folate derivative, 5,10-methylene-tetrahydrofolate is essential for the synthesis of dTMP d from dUMP and it is, therefore, crucial for DNA replication and cell division. Tetrahydrofolate is an essential substrate in the biosynthesis of amino acid, glycine. [url=http://www.llamp.net/?q=Folate biosynthesis]14[/url] The two essential precursors of folate biosynthesis are 4-aminobenzoate (a product of shikimate biosynthesis pathway) and GTP e . Thymidylate cycle, a part of folate biosynthesis pathway plays important role in the generation of amino acid glycine and dTMP. It is made of 11 enzymatic steps. Some of the carbon atoms of purines are acquired from derivatives of N10 -formyltetrahydrofolate. The methyl group of thymine, a pyrimidine, comes from N5 , N10 -methylenetetrahydrofolate. This tetrahydrofolate derivative can also donate a one-carbon unit in an alternative synthesis of glycine that starts with oxygen CO2 and ammonium NH4+ , a reaction catalyzed by glycine synthase (called the glycine cleavage enzyme when it operates in the reverse direction). 25 It is synthesized in bacteria, consists of substituted pterin (6-methylpterin), p-aminobenzoate, and glutamate moieties.
Cobalamin (vitamin B12) is the largest and most structurally complex vitamin. It consists of a modified tetrapyrrole, a corrin, with a centrally chelated cobalt and is usually found in one of two biologically active forms: methylcobalamin and adenosylcobalamin. Most prokaryotes, as well as animals, have cobalamin-dependent enzymes that use it as a cofactor, whereas plants and fungi do not use it.
Biosynthetic pathways of tetrapyrrole compounds.
ALA is synthesized by either the C4 or the C5 pathway. Adenosylcobalamin is synthesized via the de novo or via salvage pathways. The enzymes shown in the adenosylcobalamin biosynthetic pathway originate from P. denitrificans or S. typhimurium, which either use the aerobic pathway or the anaerobic pathway, respectively