Title

Comparative physiology investigations support a role for histidine-containing dipeptides in intracellular acid-base regulation of skeletal muscle

Document Type

Journal Article

Publication Title

Comparative Biochemistry and Physiology, Part A

ISSN

1531-4332

Volume

234

First Page

77

Last Page

86

PubMed ID

31029715

Publisher

Elsevier

School

School of Medical and Health Sciences

Grant Number

ARC Number : DP140104165

Comments

Originally published as: Dolan, E., Saunders, B., Harris, R. C., Bicudo, J. E. P. W., Bishop, D. J., Sale, C., & Gualano, B. (2019). Comparative physiology investigations support a role for histidine-containing dipeptides in intracellular acid–base regulation of skeletal muscle. Comparative Biochemistry and Physiology, Part A, 234, 77-86. Original publication available here

Abstract

Histidine containing dipeptides (HCDs: carnosine, anserine and balenine) have numerous therapeutic and ergogenic properties, but there is a lack of consensus on the mechanistic pathways through which they function. Potential roles include intracellular buffering, neutralisation of reactive species, and calcium regulation. Comparative investigations of the HCD content of various species provide unique insight into their most likely mechanisms of action. This review chronologically describes how the comparative physiology studies, conducted since the beginning of the 20th century, have shaped our understanding of the physiological roles of HCDs. The investigation of a wide range of physiologically distinct species indicates that those species with a strong reliance on non-oxidative forms of energy production are abundant in HCDs. These include: whales who experience long periods of hypoxia while diving; racehorses and greyhound dogs who have highly developed sprint abilities, and chickens and turkeys whose limited capacity for flight is largely fuelled by their white, glycolytic, muscle. Additionally, a higher HCD content in the Type 2 muscle fibres of various species (which have greater capacity for non-oxidative metabolism) was consistently observed. The pKa of the HCDs render them ideally suited to act as intracellular physicochemical buffers within the pH transit range of the skeletal muscle. As such, their abundance in species which show a greater reliance on non-oxidative forms of energy metabolism, and which experience regular challenges to acid-base homeostasis, provides strong evidence that intracellular proton buffering is an important function of the HCDs in skeletal muscle.

DOI

10.1016/j.cbpa.2019.04.017

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