Textbook - BIOLOGICAL CHEMISTRY - Gubsky Yu.I. - 2000

Chapter II. GENERAL PRINCIPLES OF METABOLISM

CHAPTER 10. THE TRICARBOXYLIC ACID CYCLE

10.4. ANAPLEROTIC AND AMPHIBOLIC REACTIONS

Anaplerotic reactions are cellular METABOLISM pathways that increase the concentration of Tricarboxylic Acid Cycle substrates by generating them from intermediates of other metabolic pathways (specifically, Amino Acids and Pyruvate). By activating the TCA cycle, anaplerotic reactions help drive and intensify catabolic processes within the body.

Generation of TCA cycle substrates via anaplerotic reactions.

1. Conversion of amino acids into dicarboxylic acids, which serve as TCA cycle substrates:

- formation of α-ketoglutarate through Transamination reactions;

- formation of oxaloacetate through transamination reactions;

- formation of α-ketoglutarate via the Glutamate dehydrogenase reaction;

- formation of succinyl-CoA from isoleucine, valine, Methionine, and Threonine.

2. Formation of oxaloacetate from pyruvate via the pyruvate carboxylase reaction:

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The coenzyme for pyruvate carboxylase is biotin (vitamin H), which reversibly accepts CO₂ during the reaction to form N-carboxybiotin.

Pyruvate carboxylase is an allosteric enzyme positively modulated by acetyl-CoA. Under conditions of low intracellular acetyl-CoA, enzyme activity and The rate of the pyruvate carboxylase reaction remain low. Conversely, the accumulation of acetyl-CoA—observed during the activation of catabolic processes—stimulates the TCA cycle via oxaloacetate synthesis, thereby enhancing The oxidation of its primary substrate, acetyl-CoA.

The conversion of pyruvate into oxaloacetate by pyruvate carboxylase is a critical anaplerotic reaction in Liver and Kidney Cells.

3. Formation of oxaloacetate from phosphoenolpyruvate:

This reaction is catalyzed by phosphoenolpyruvate carboxykinase. It involves the Synthesis of the high-energy nucleoside triphosphate GTP, driven by the Cleavage of the high-energy bond within phosphoenolpyruvate, a Glycolysis metabolite.

The phosphoenolpyruvate carboxykinase reaction acts as an anaplerotic pathway for the TCA cycle in the myocardium and other Muscle Tissues. When running in reverse, this same reaction is utilized in glucose synthesis.

Amphibolic reactions are pathways that utilize TCA cycle substrates to produce intermediates essential for biosynthetic processes:

1) reactions reverse to The amino acid transformations discussed above can function amphibolically—in this case, dicarboxylic acids produced in the TCA cycle stimulate Protein Synthesis;

2) a key reaction in glucose synthesis (Gluconeogenesis) is The formation of phosphoenolpyruvate from oxaloacetate and GTP, which is simply the phosphoenolpyruvate carboxykinase reaction operating in the reverse direction of the anaplerotic process mentioned above.