| Chem 432 |
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Spring 2002 |
| Lecture Notes:: 28 January |
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Tetrahydrofolate is the major carrier involved in single carbon transfers. As can be seen in the Main Folate Metabolic Pathways diagram, H4-folate can carry carbon in the various oxidation states required in a variety of metabolic reactions:
Tetrahydrofolate is made from the vitamin folate by reducing the 5, 6, 7, and 8 positions of the pteridine ring with two sequential DH reactions using NADPH:
Folate itself is composed of three components as shown on the figure.
Methionine. Methionine is essential for protein biosynthesis. It is also used as a source for carbons, and as a carrier for activated carbons in the one-carbon pool. In addition it serves as the source of Sulfur in cysteine biosynthesis. The latter three all involve methyl group transfers. The terminal methyl group on met is activated via reaction with ATP to give S-Adenosylmethionine, phosphate and pyrophosphate (= 2.5 ATP equiv. at a cost of 3 ATP's). This give the high-energy sulphonium group:
S-Adenosylmethionine can now donate its activated methyl group.
We've been looking at the sources and carriers for carbon in the one-carbon pool, we can now look at some main uses for these carbons.
S-Adenosylmethionine can now donate its activated methyl group. For example creatine is synthesized as shown below, starting with glycine:
Note that arginine provides "most of a urea" just as it does in the Urea Cycle, but here it is transferred to glycine instead of to water. This is a fairly active synthesis since P-creatine spontaneously and irreversibly cyclizes to creatinine, which is then excreted as waste.
Choline is synthesized by methylating ethanolamine on Phosphatidyl ethanolamine three times using S-Adenosylmethionine as the source of methyl groups:
The phosphatidyl choline can then be used as a membrane lipid, or choline can be hydrolyzed off to give the free molecule for acetyl choline synthesis. The phosphatidyl ethanolamine is derived from phosphatidyl serine (via a PLP catalyzed decarboxylation). Since serine can be synthesized from glucose, choline can be biosynthesized de novo.
S-Adenosylmethionine is obviously an important source of carbon groups in biosynthesis. There are two main pathways for regenerating it from S-Adenosylhomocysteine. First it may be regenerated by homocysteine methyltransferase (coenzyme B12-dependent) using 5-methyl H4-folate as a methyl group source. In this case glucose may thus serve as the ultimate source of the methyl group:
Alternatively it can be regenerated using choline as the source of the methyl group:
The N,N-dimethyl glycine can be oxidized further to give two formaldehydes and glycine.
S-Adenosyl homocysteine may also be irreversibly degraded. Adenosine is first hydrolyzed off. The thiol group of the resulting homocysteine then attacks the a-methyl carbon of serine displacing the hydroxyl group to give water and cystathionine (catalyzed by cystathionine b-synthase, requires PLP). Hydrolysis by cystathionine gamma-lyase (PLP requiring)
Before we leave the amino acids I want to look at some related processes, the first of which, Nitrogen fixation, is restricted to prokaryotes.
Nitrogen is one of the four most common elements in all living organisms. The problem is that although nitrogen is very common in its elemental form, the N2 molecule is very stable - the triple bond has an energy of 945 kJ/mol (vs. around 350 kJ/mol for single bonds) and is kinetically stable as well, and is thus unavailable to most organisms. Conversion of elemental nitrogen to usable forms, e.g. NH3 or NO3- (nitrogen fixation) occurs to a limited extent via lightning discharges (about 10% of naturally fixed N2 and via a complex process carried out by some bacteria and cyanobacteria.
All biological nitrogen fixing systems have 5 basic requirements:
Nitrogen fixation is a biologically expensive process, costing 16 ATP's and 8 electrons per N2, as seen in the reaction stoichiometry:
 Pathway Diagrams |
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Last modified 28 January 2002
