Branched-Chain Amino Acids: Enzyme and Substrate Regulation

Abstract

The three branched-chain amino acids (BCAAs) are the most hydrophobic of the amino acids and play crucial roles in determining the structures of globular proteins as well as the interaction of the transmembrane domains of membranous proteins with phospholipid bilayers. However, the three BCAAs do not behave identically. In terms of protein secondary structure, valine and isoleucine exhibit a definite preference for the beta-structure, whereas leucine has a higher preference for the alpha-helix. Although mutation of one BCAA to another is commonly regarded as conservative, there are well-documented examples of such substitutions that have a significant effect on protein function. The occurrence of BCAA in nature is, therefore, attributable to their primary role in protein structure, not to their secondary metabolic roles. These functions are important for almost all proteins; therefore, BCAA commonly account for approximately 20-25% of most dietary proteins. Dietary BCAA largely escape first-pass splanchnic metabolism. The first steps in their catabolism are common to all three, involving the BCAA aminotransferase (BCAT) and branched-chain alpha-keto acid dehydrogenase (BCKD). Their further metabolism employs distinct pathways to different end-products (glucose and/or ketone bodies). However, the fact that the flux-generating step for the catabolism of the three BCAAs occurs at one of the common steps indicates that the production of these downstream products are not individually regulated and, hence, may not play important individual roles. The catabolism of the BCAAs is highly regulated by both allosteric and covalent mechanisms. BCKD is inhibited by phosphorylation and activated by dephosphorylation. Allosteric inhibition of the kinase by the branched-chain keto acids (BCKA) (particularly by alpha-ketoisocaproate) serves both as a mechanism for promoting the catabolism of excess quantities of these amino acids as well as for conserving low concentrations of these dietary essential amino acids. Cytosolic and mitochondrial isoenzymes of BCAT have been identified. They are thought to play an important role in brain neurotransmitter metabolism.

Male lifespan extension with 17‐α estradiol is linked to a sex‐specific metabolomic response modulated by gonadal hormones in mice

“…Furthermore, valine is exclusively glucogenic, while isoleucine is both keto‐ and glucogenic and leucine is exclusively ketogenic. Thus, although the concentration of these amino acids is often highly correlated, their metabolism can differ in a state and tissue‐specific manner (Brosnan & Brosnan 2006). Indeed, while long lifespan has been associated with elevations in selected amino acids in previous studies, the published work has sometimes documented a lack of concordance in BCAA responses.…”

Biochemistry of apple aroma: A review

“…First, the α-keto acid is irreversibly converted to a branched-chain acyl-CoA (2-methyl butanoil-CoA, 4-methyl butyl-CoA and 2-methyl propyl-CoA from Ile, Leu and Val, respectively) (141,149) by the action of branched-chain α-keto acid dehydrogenase (BCKDH), which substitutes a CO 2 from the 2-oxo acid for the CoA cofactor with NAD + reduction (140). Then, the acyl-CoA can be converted to a fatt y acid by phosphate acetyltransferase (PAT) (18,140).…”

Aspectos atuais sobre aminoácidos de cadeia ramificada e exercício físico

“…Tanto a isoleucina quanto a valina são metabolizadas para succinato via metilmalonil-CoA. O outro produto do metabolismo da isoleucina é o acetoacetato e, desse modo, a isoleucina pode ser considerada como um aminoácido glicogênico e cetogênico (Figura 2) (Brosnan, Brosnan, 2006;Harper, Miller, Block, 1984). …”