Oxidation of Energy Substrates in Tissues of Fish: Metabolic Significance and Implications for Gene Expression and Carcinogenesis.

Fish are useful animal models for studying effects of nutrients and environmental factors on gene expression (including epigenetics), toxicology, and carcinogenesis. To optimize the response of the animals to substances of interest (including toxins and carcinogens), water pollution, or climate changes, it is imperative to understand their fundamental biochemical processes. One of these processes concerns energy metabolism for growth, development, and survival. We have recently shown that tissues of hybrid striped bass (HSB), zebrafish, and largemouth bass (LMB) use amino acids (AAs; such as glutamate, glutamine, aspartate, alanine, and leucine) as major energy sources. AAs contribute to about 80% of ATP production in the liver, proximal intestine, kidney, and skeletal muscle tissue of the fish. Thus, as for mammals (including humans), AAs are the primary metabolic fuels in the proximal intestine of fish. In contrast, glucose and fatty acids are only minor metabolic fuels in the fish. Fish tissues have high activities of glutamate dehydrogenase, glutamate-oxaloacetate transaminase, and glutamate-pyruvate transaminase, as well as high rates of glutamate uptake. In contrast, the activities of hexokinase, pyruvate dehydrogenase, and carnitine palmitoyltransferase 1 in all the tissues are relatively low. Furthermore, unlike mammals, the skeletal muscle (the largest tissue) of HSB and LMB has a limited uptake of long-chain fatty acids and barely oxidizes fatty acids. Our findings explain differences in the metabolic patterns of AAs, glucose, and lipids among various tissues in fish. These new findings have important implications for understanding metabolic significance of the tissue-specific oxidation of AAs (particularly glutamate and glutamine) in gene expression (including epigenetics), nutrition, and health, as well as carcinogenesis in fish, mammals (including humans), and other animals.