Fatty acid biosynthesis pathway

The fatty acid biosynthesis pathway communicates with at least three other metabolic pathways either by sharing common intermediates or by regulatory mechanisms. Fill in the table below. 

A considerable amount of knowledge has accumulated about how pheromone components are produced in female moths since the first pathway was identified some 20 years ago. It appears that most female moths produce their pheromone through modifications of fatty acid biosynthesis pathways. For moths that utilize aldehydes, alcohols, or esters biosynthesis occurs in the pheromone gland. The exceptions are those that utilize linoleic or linolenic acids, which must be obtained from the diet. However, modifications of these fatty acids occur in the gland. For moths that utilize hydrocarbons or epoxides of hydrocarbons, the hydrocarbon is produced in oenocyte cells and then transported to the pheromone gland where the epoxidation step takes place. 

The net effect of the eiglit steps in the fatty-acid biosynthesis pathway is to take two 2-carbon acetyl groups and combine them into a 4-carbon butyryi group. Further condensation of the butyryi group with another malonyl ACP yields a 6-carbon unit, and still further repetitions of the pathway add two more carbon atoms to the chain each time until the 16-carbon palmitoyl ACP is reached. 

The biotin biosynthetic pathway is outlined in Fig. 25 [115]. Pimeloyl-CoA, synthesized by a variation of the fatty acid biosynthesis pathway, is condensed with alanine to give 142. 

In discussions on the mechanisms of the enzymes involved in each pathway, there will be a particular focus on three superfamilies enzymes that share the thiolase fold and catalyze carbon—carbon bond formation and cleavage reactions catalyzed by NAD(P)-dependent enzymes in the fatty acid biosynthesis pathway involve proteins that are members of the short-chain dehydrogenase reductase (SDR) superfamily and finally there are mechanistic parallels between the hydration and dehydration reactions in each pathway with a particular focus on the crotonase superfamily. 

Polyketides are a class of antibiotics found in bacteria and fungi. Erythromycin and oxytetracycline are examples. The pathway for polyketide synthesis contains part of the fatty acid biosynthesis pathway, except that one or more of the enzymes are missing at various points in the pathway (Figure 18.35). This leads to a diverse set of products containing internal hydroxyls and ketone groups. 

The fatty acid biosynthesis pathway presents us with the first example of an interesting puzzle. If all the oxidative metabolism of foodstuffs is tied into making NADH (to be reoxidised and to make ATP), how do we get a supply of NADPH for biosynthesis What reduces the NADP+ ... 

The next enzyme in the fatty acid biosynthesis pathway is the acetyl-CoA carboxylase. The acetyl-CoA carboxylase from grasses (Poaceae) can specifically be blocked by herbicides (see Fig. 3) of the cyclohexane-1,3-dione (sethoxydim, cycloxydim, clethodim) and aryloxyphenoxypropionic acid-type (diclofop, fenoxaprop, haloxyfop, fluazifop) which was shown by us only recently (Focke and Lichtenthaler 1987, Kobek et al. 1988). 

Figure 2 depicts MCL-PHA monomer supplying pathways from non-related carbon sources such as glucose. In all three pathways, monomers are derived from the fatty acid biosynthesis pathway. 

Figure 2. Medium-chain-length (MCL) PHA production from non-related carbon sources. A. The fatty acid biosynthesis pathway. B. FabH and FabG mediated SCL-MCL PHA monomer supply. C. 3-hydroxyacyl-ACP CoA transacetylase (PhaG) mediated MCL PHA monomer supply. D. Thioesterase A (TesA) mediated MCL PHA monomer supply (via the P-oxidation pathway).

This study has shown that SCL and MCL PHA monomer supply from glucose is enhanced by overexpression of genes for the fatty acid biosynthesis en2ymes (fabH and fabG) in recombinant E. coli. SCL-MCL PHA copolymers with a relatively low mol% of MCL monomer incorporated were produced by recombinant E. coli and the resultant was dramatically reduced compared to that of P(3HB) homopolymer. The use of the fatty acid biosynthesis pathway for SCL and MCL PHA monomer supply provides a foundation from which more robust methods for the production of SCL-MCL PHA copolymers from non-related carbon sources can be developed. 

With ethyl-AMP and AMPI specific inhibitors of the two independent routes of acetyl-CoA formation in plastids are available. Several specific xenobiotics block efficiently de novo fatty acid biosynthesis at different steps and enzyme levels (Figure 3). Graminicides such as diclofop, sethoxydim or cycloxydim are specific inhibitors of acetyl-CoA carboxylase (ACCase) of grasses [10], the antibiotics cerulenin and thiolactomycin are inhibitors which affect certain of the li-ketoacyl-ACP synthases (KAS I, II and III). With these xenobiotics one can control the metabolite flow through the fatty acid biosynthesis pathway and obtain a better understanding of the regulation of the plants de novo fatty acid biosynthesis and the enzymes involved. 

Figure 3 Scheme of de novo fatty acid biosynthesis pathway from acetate and pyruvate with indication of the site of action of several inhibitors. 

Figure 1. The elongation cycle of the fatty acid biosynthesis pathway consists of a condensation reaction followed by three subsequent steps to remove the keto-group from the growing carbon chain. The last of these three steps is catalyzed by the Enoyl-ACP reductase.

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