L-valine in energy metabolism

As one of the branched-chain amino acids (BCAAs), the conversion pathway of L-valine in energy metabolism centers on catabolism, ultimately providing energy for cells by entering the tricarboxylic acid cycle (TCA cycle). The specific process can be divided into three core stages:

I. Transamination and Dehydrogenation Reactions in the Cytoplasm

The decomposition of L-valine initiates in the cytoplasm, undergoing initial transformation through two key enzymes:

Transamination catalyzed by branched-chain amino acid transaminase (BCAT): Under the action of BCAT (existing in cytoplasmic BCATc and mitochondrial BCATm), L-valine transfers its amino group to α-ketoglutarate, generating α-ketoisovalerate (α-KIVA) and glutamic acid. This step is critical for amino acid deamination, and the reaction is reversible—when cells need to synthesize valine, the reverse reaction can occur, but in scenarios dominated by energy metabolism, the reaction mainly proceeds in the catabolic direction.

Oxidative decarboxylation catalyzed by branched-chain α-ketoacid dehydrogenase complex (BCKDC): After α-ketoisovalerate enters the mitochondria, it undergoes oxidative decarboxylation catalyzed by BCKDC (a multi-enzyme complex composed of E1α, E1β, E2, and E3 subunits). This reaction requires coenzyme A (CoA) participation, producing isobutyryl-CoA while releasing CO₂ and NADH (reduced nicotinamide adenine dinucleotide). BCKDC activity is regulated by phosphorylation/dephosphorylation: when cellular energy is sufficient, kinases phosphorylate and inactivate BCKDC; when energy demand increases (e.g., during exercise or starvation), phosphatases activate BCKDC to accelerate valine decomposition.

II. β-Oxidation and Acyl-CoA Conversion in the Mitochondrial Matrix

Isobutyryl-CoA undergoes β-oxidation-like reactions in mitochondria, gradually decomposing into intermediates that can enter the TCA cycle:

Dehydrogenation catalyzed by isobutyryl-CoA dehydrogenase: Isobutyryl-CoA undergoes dehydrogenation with FAD as a coenzyme under the action of isobutyryl-CoA dehydrogenase, generating methacrylyl-CoA and producing FADH₂ (reduced flavin adenine dinucleotide). This step is characteristic of β-oxidation, driving subsequent decomposition through double bond formation.

Hydration and re-dehydrogenation: Methacrylyl-CoA is hydrated under the catalysis of enoyl-CoA hydratase to form β-hydroxyisobutyryl-CoA; subsequently, this product undergoes dehydrogenation with NAD⁺ as a hydrogen acceptor under the action of β-hydroxyacyl-CoA dehydrogenase, generating β-ketoisobutyryl-CoA and producing NADH.

Thiolysis to generate acetyl-CoA and propionyl-CoA: β-ketoisobutyryl-CoA reacts with CoA under the action of thiolase, undergoing carbon chain cleavage to generate acetyl-CoA and propionyl-CoA. These two products are key nodes entering the core pathway of energy metabolism—acetyl-CoA can directly enter the TCA cycle, while propionyl-CoA requires further conversion.

III. Carboxylation of Propionyl-CoA and Integration into the TCA Cycle

Propionyl-CoA, containing 3 carbon atoms, cannot directly enter the TCA cycle and must be converted into TCA cycle intermediates through carboxylation:

Generation of methylmalonyl-CoA catalyzed by propionyl-CoA carboxylase: In mitochondria, propionyl-CoA combines with CO₂ under the action of propionyl-CoA carboxylase (dependent on biotin and ATP) to form D-methylmalonyl-CoA.

Isomerization and entry into the TCA cycle: D-methylmalonyl-CoA is converted to the L-form by methylmalonyl-CoA epimerase, then rearranged by methylmalonyl-CoA mutase (dependent on vitamin B₁₂) to generate succinyl-CoA—a key intermediate of the TCA cycle that can directly participate in the cycle and produce ATP through oxidative phosphorylation.

Energy Output and Physiological Significance

In the complete decomposition of L-valine, each molecule produces approximately 16.5 molecules of ATP: NADH and FADH₂ generated by dehydrogenation reactions contribute 3 or 2.5 molecules of ATP and 1.5 molecules of ATP, respectively, through respiratory chain oxidation, while succinyl-CoA further provides energy through substrate-level phosphorylation and oxidative phosphorylation after entering the TCA cycle. This pathway is particularly active in muscle cells—when the body is in a state of increased energy demand (e.g., starvation, high-intensity exercise), muscle tissue preferentially decomposes BCAAs (including valine) to supplement TCA cycle intermediates through the above pathway, maintaining energy homeostasis. Meanwhile, its decomposition products can be converted into glucose in the liver through gluconeogenesis to provide energy for glucose-dependent organs such as the brain, reflecting the synergistic connection between amino acid metabolism and glucose metabolism.