Question

Leucine can be well absorbed by any part of the body. What could be the mechanism of absorption for this molecule?

Answer 1

Solution:-

The branched-chain amino acid leucine has been well studied for its ability to promote positive nitrogen balance as both a protein precursor and a signaling molecule in muscle of rats, piglets and humans. Leucine has also been shown to decrease muscle protein breakdown in humans. Leucine serves as a substrate for protein synthesis that occurs in the splanchnic bed and in skeletal muscle. Leucine not incorporated into splanchnic or skeletal muscle protein undergoes complex metabolism yielding several intermediate molecules and is ultimately oxidized . The first intermediate molecule yielded by leucine metabolism, α-ketoisocaproic acid (KIC), is formed when leucine is reversibly transaminated within the muscle by mitochondrial branched-chain amino transferase (mBCAT). A proportion of KIC is a substrate for branched-chain alpha-keto acid dehydrogenase complex (BCKDC), which irreversibly and oxidatively decarboxylates KIC to form isovaleryl-CoA. Alternatively, a fraction of KIC is decarboxylated and reduced in liver to yield β-hydroxy-β-methylbutyrate (HMB), also known as β-hydroxyisovalerate. This reaction is catalyzed by ketoisocaproate dioxygenase (4-hydroxyphenylpyruvate dioxygenase which has been detected in the livers of rats and humans .In biotin-deficient or valproate-treated patients, HMB can also be formed from leucine by the “ESCH 1 pathway”, which involves dehydrogenation of isovaleryl-CoA to methylcrotonyl-CoA, and conversion of methylcrotonyl-CoA to 3-hydroxyisovaleryl-CoA by short-chain enoyl-CoA hydratase.

HMB is a metabolite of interest because it has been shown to have some of the anabolic and anti-catabolic effects of leucine on muscle cells, particularly in highly catabolic conditions such as experimentally induced cancer cachexia, bed rest immobilization , and sepsis. In the catabolic state, HMB helps stimulate muscle protein synthesis and inhibit breakdown by reducing proteasome activity and expression of the 20S subunit of the proteasome ,by inhibition of apoptosis ,and by activation of satellite cells.

Leucine conversion to HMB has been documented in vivo in sheep and pigs and in humans with biotin deficiency or treated with the drug valproate. However, the metabolic profile of leucine has not been detailed in a rat ADME model. We wanted to explore the absorption, distribution, metabolism, and excretion of leucine using a standard ADME model, the Sprague–Dawley rat.14C-leucine indicates that conversion to HMB occurs in the rat and is quantifiable in both plasma and urine.