Metabolic pathways rate-limiting reactions

Controlling an Enzyme That Catalyzes a Rate-Limiting Reaction Regulates an Entire Metabolic Pathway... 

Each metabolic pathway has a committing reaction, which may or may not be identical to the rate-limiting reaction. This committing reaction designates the fate of an intermediate. In Equation (5.39), it is D —> G for I and D — E for F. 

In a metabolic pathway that does not contain any allosteric enzymes, of the enzymes involved, the rate-limiting reaction enzyme will have the... 

EIGEN-TAMM MECHANISM Rate-limiting step in metabolic pathway, PACEMAKER REACTION RATE OF APPEARANCE CHEMICAL KINETICS RATE OF DISAPPEARANCE CHEMICAL KINETICS... 

Metabolic control can be understood to some extent by focusing attention on those enzymes that catalyze rate-limiting steps in a reaction sequence. Such pacemaker enzymes1-4 are often involved in reactions that determine the overall respiration rate of a cell, reactions that initiate major metabolic sequences, or reactions that initiate branch pathways in metabolism. Often the first step in a unique biosynthetic pathway for a compound acts as the pacemaker reaction. Such a reaction may be described as the committed step of the pathway. It usually proceeds with a large decrease in Gibbs energy and tends to be tightly controlled. Both the rate of synthesis of the enzyme protein and the activity of the enzyme, once it is formed, may be inhibited by feedback inhibition which occurs when an end product of a biosynthetic pathway accumulates... 

A metabolic pathway consists of a sequence of enzyme-catalyzed steps. The pathway usually has a rate-limiting step, the reaction in the sequence with the lowest velocity. This may be due to the enzyme having a high Km for its substrate or to the enzyme being subject to inhibition by a negative effector, usually a product of the pathway. In the latter case, an allosteric enzyme is involved. 

The reaction catalyzed by delta-6-desaturase enzyme is the slowest reaction in the metabolic pathway of LA and is considered as a rate-limiting step (4, 5). Activity of this enzyme further decreases with age and in people suffering from various diseases, including arthritis, diabetes, hypertension, eczema, psoriasis, and so on. Lifestyle factors like stress, smoking, excessive consumption of alcohol, linoleic acid (6), saturated and trans-fatty acids and nutritional deficiencies of Vitamin B6, zinc (7), and magnesium inhibit this desaturase. As a result of limitations in in vivo production of GLA, supplementation with preformed GLA is becoming important. This has led to interest in development and commercialization of the sources of GLA. 

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