Metabolite flow regulation

Metabolite flow along a metabolic pathway is mainly determined by the activities of the enzymes involved (see p. 88). To regulate the pathway, it is suf cient to change the activity of the enzyme that catalyzes the slowest step in the reaction chain. Most metabolic pathways have key enzymes of this type on which the regulatory mechanisms operate. The activity of key enzymes is regulated at three independent levels ... 

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. 

Modulation by ligands. An important variable that regulates flow through a metabolic pathway is precursor availability (metabolite A in the case shown here). The availability of precursor A increases along with the activity of the metabolic pathways that form A (3) and it decreases with increasing activity of other pathways that also consume A (4). Transport from one cell compartment to another can also restrict the availability of A. 

The flow of metabolites through the citric acid cycle is under stringent regulation. Three factors govern the rate of flux through the cycle substrate availability, inhibition by accumulating products, and allosteric feedback inhibition of the enzymes that catalyze early steps in the cycle. 

In the preceding discussion of enzyme activity, little was said about the overall regulation and coordination of these activities within a smoothly functioning cell. Clearly, the flow of metabolites through anabolic and catabolic pathways must be consistent with the requirements of the cell (and the organism) and effectively respond to both short- and long-term perturbations in the intracellular and extracellular environment. There are many mechanisms that affect enzyme activity, and the more important ones are summarized below. 

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