[Frontiers in Bioscience 17, 2725-2739, June 1, 2012]

Nutritional and regulatory role of branched-chain amino acids in lactation

Jian Lei1, Dingyuan Feng1, Yongliang Zhang1, Feng-Qi Zhao2, Zhenlong Wu3, Ana San Gabriel4, Yoshiyuki Fujishima4, Hisayuki Uneyama4, Guoyao Wu3,5

1College of Animal Science and Technology, South China Agricultural University, Guangzhou, P. R. China 510642, 2Department of Animal Science, University of Vermont, Burlington, VT, USA 05405,3State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China 100193,4Institute for Innovation, Ajinomoto Inc., 15-1, Kyobashi 1-chome, Chuo-ku, Tokyo, Japan 104-8315,5Department of Animal Science and Faculty of Nutrition, Texas A&M University, College Station, TX, USA 77843-2471

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. BCAA catabolism in mammary epithelial cells
3.1. BCAA degradation
3.2. Role of milk-born glutamine, glutamate and aspartate for suckling neonates
4. Role of BCAA in cell signaling to support lactogenesis
4.1. The biochemical machinery of milk production
4.2. BCAA stimulate growth and proliferation of mammary epithelial cells
4.3. BCAA and the mTOR signaling pathway
4.4. BCAA enhance the functional differentiation of mammary epithelial cells
4.5. BCAA increase the longevity of mammary epithelial cells
5. BCAA regulate mammary metabolic capacity for milk synthesis
5.1. Intracellular protein synthesis
5.2. Intracellular protein degradation
6. Dietary supplementation with BCAA to lactating mammals improves milk production and neonatal growth
6.1. Low availability of dietary glutamine for mammary tissue in lactating dams
6.2. Dietary BCAA supplementation enhances milk production in animals
7. Conclusion and perspectives
8. Acknowledgments
9. References

1. ABSTRACT

Optimal growth and health of suckling neonates critically depend on milk production by their mothers. In both humans and animals, branched-chain amino acids (BCAA) are not only the major components of milk proteins but are also nitrogenous precursors for the synthesis of glutamate, glutamine, alanine, and aspartate in the mammary gland. These synthetic pathways, which are initiated by BCAA transaminase, contribute to the high abundance of free and peptide-bound glutamate, glutamine, aspartate and asparagine in milk. In mammary epithelial cells, the carbon skeletons of BCAA can be partially oxidized via branched-chain α-ketoacid dehydrogenase to provide energy for highly active metabolic processes, including nutrient transport, protein turnover, as well as lipid and lactose syntheses. In addition, results of recent studies indicate that BCAA play regulatory roles in mammary metabolism. For example, leucine can activate the mammalian target of rapamycin cell signaling pathway to enhance protein synthesis in mammary epithelial cells. Dietary supplementation with BCAA may have great potential to enhance milk synthesis by the lactating mammary gland, thereby improving neonatal survival, growth and development.