Nutrition and Gene Expression

Carolyn D. Berdanier

• Publisher: CRC Press
• Year: 2018
• Print ISBN: 9781315896014
• eBook ISBN: 9781351092012
• Topic: Medicine
• Subtopic: Nutrition, Dietics & Bariatrics

Nutrition and Gene Expression is devoted to exploring the tissue-specific and developmental aspects of the interaction between nutrients and the genome. The book discusses chemical sensitivity in relation to the ability of cells to detect nutrients; reviews the means by which lower organisms respond to nutrients; and provides examples on how each of the classes of nutrients affects genetic transcription, mRNA translation or stability. The receptor-mediated actions of vitamin D and retinoic acid on gene expression are discussed, including the case of bone formation and dissolution. Other important topics covered in the volume include newly discovered effects of fatty acids on regulating gene expression, the effects of diet on mRNA editing, the interplay between dietary carbohydrates and proteins in regulating metabolism of liver cells, the effects of metal ions on protein synthesis, and much more. Nutrition and Gene Expression is an important reference for nutritionists, physiologists, biochemists, clinical nutritionists, pharmaceutical researchers, geneticists, and food scientists.

Chapter 1
Nutrient Receptors And Gene Expression

James L. Hargrove and Carolyn D. Berdanier

Table of Contents

1. I. Introduction
2. II. The Evolution of Genetic Control Mechanisms
3. III. Elements of Genetic Control
4. IV. The Importance of Receptors in Nutrient-Gene Interactions
5. V. Nutritional Regulation of Genes in Unicellular Organisms
   1. A. Nutrient-Gene Interactions in Bacteria
   2. B. Nutritional Regulation of Genes in Yeast
6. VI. Nutrient Sensors in Mammals
7. VII. Temporal and Quantitative Aspects of Gene Expression
8. VIII. Conclusions and Prospects
9. References

I. Introduction

The scope of potential nutrient-gene interactions is enormous. More than 40 nutrients are known to be essential to mammals, and health may be impaired by a deficit in any one of them.¹ Normal growth, reproduction, immune function, and lifespan require adequate intakes of foods containing these essential dietary constituents. Just as deficient intakes can be deleterious, excessive intakes can also be harmful, as is true for vitamins A and D, selenium, iron, and total caloric intake. Genes are thought to play a fundamental role in adaptation to the day-to-day variability in nutrient supply, such that the nutritional status and health of the individual can be relatively constant despite the variable supply. That compensatory mechanisms exist is not in doubt.^2–5 However, the means by which individual nutrients are detected by cells, and the details of how altered nutrient supply leads to a reprogramming of the genetic apparatus, are still lacking in many important cases.

Not only is the current explosion in genetic technology increasing our understanding of how genetic mechanisms participate in monitoring nutrient supply and utilization, it is also clear that genes participate in higher order processes such as food-seeking behavior. Ingestion of nutrients quickly activates complex neural and endocrine circuits that affect gene expression not only in the gut and peripheral tissues, but also in the brain. Genes are activated as a means of feedback control to deal with undersupply and oversupply of particular nutrients, which requires the central nervous system to integrate internal, metabolic cues and environmental conditions.

The purpose of this chapter is to provide a context for the topic of nutrient-gene interactions, starting with the question of how the transducing systems that mediate such effects may have arisen during evolution. Even though few mammalian systems have been characterized that show direct effects of nutrients on genes, numerous examples are under study in microorganisms, and some of these are described to illustrate some of the means by which nutrients may affect genetic activity in the absence of hormonal mediators. Next, the presence of nutrient-sensitive chemoreceptors in mammals is discussed, including neural and endocrine mechanisms. To complete this general introduction, temporal and quantitative aspects of gene expression in mammals are reviewed.

II. The Evolution Of Genetic Control Mechanisms

Evolutionary theory postulates that present-day genetic mechanisms are inherited from ancestral patterns that have been modified by mutation, variation, and natural selection during competition for limited resources. Foremost among those limited resources are the nutrients, which are defined as any chemical substances that are necessary to life processes such as cellular metabolism, reproduction, motility, and sensation. Because the availability of nutrients has always been sporadic, organisms that are best able to detect, take up, and assimilate nutrients have the best chance of contributing their genotype to the next generation so that it is maintained in the population.

Implicit in the theory of evolution is the idea of feedback control; living organisms can not function optimally unless they are able to detect and use information concerning the environment. The nutrients found in food can not be detected unless they interact specifically with appropriate components, such as ligand-binding proteins that may be linked to processes for their uptake or utilization. The need to detect concentrations indicates that nutrients serve two distinct functions: one which is a metabolic function and one which is informational. These two functions may be related; for example, glucose both provides energy to the pancreatic ß-cells and generates a signal that promotes insulin secretion. The functions may also be separate, as in the use of glutamic acid for neuronal protein synthesis or for neurotransmission.

Appropriate regulation of genes in response to diet requires two types of controlling elements. The first is a means of sensing the level of nutrient that is present; this is the function of sensors or receptors, which may detect one particular nutrient, members of one class of nutrients, or hormones secreted in response to the nutrients. We are most familiar with this aspect of nutrients through the senses of taste and smell, by which neuronal chemoreceptors detect the presence of sugars, amino acids, salts, and other substances. Second, there must be a transducing mechanism by which the level of nutrient affects cellular activities, including the activity of genes that regulate the processes by which nutrients are used.

How might organisms have acquired the capacity to bind nutrients with specificity and to use them in feedback control circuits? The exon-shuffling hypothesis suggests that discrete segments of DNA encode units of structure and function in mRNAs and proteins. These unitary elements may be recombined to produce new molecules with two or more structural or functional elements. This theory is now being applied to analyze functional elements in genes that encode nutrient receptors and enzymes that participate in nutrient metabolism. For instance, plasma membranes of hepatocytes and Kupffer cells contain lectins, or receptors that bind carbohydrates.⁶ The carbohydrate-binding portion of the proteins is located at the carboxylic terminals and is encoded by three exons at the 3' end of the gene. However, in the related mannose-binding protein, a single exon encodes the binding function. Separate exons encode a transmembrane domain and other structural elements.

Current theory based on the exon-shuffling hypothesis suggests that most mammalian proteins belong to superfamilies whose members originated by recombination of exons that encoded short functional domains. Subsequent mutations and recombination then caused divergence among family members. Another example of this mechanism is the gene for the vitamin D-binding protein; the gene contains 13 exons.⁷ This protein contains a single binding site for sterols such as 25-hydroxy D₃ that is thought to be encoded at the 5' end of the gene on exons 1 and 2. The protein is multifunctional, and a region that binds actin may be encoded on exon 10.⁷ Vitamin D-binding protein is thought to b...

Table of contents

• Cover
• Title
• Copyright
• Preface
• Editors
• Contributors
• Contents
• Chapter 1 Nutrient Receptors and Gene Expression
• Chapter 2 Lactose Intolerance and Regulation of Small Intestinal Lactase Activity
• Chapter 3 Regulation of Gastrointestinal Lipase Gene Expression by Dietary
• Chapter 4 Nutritional Control of Gastrointestinal Hormone Gene Expression
• Chapter 5 Calcium Homeostasis, Endoplasmic Reticular Function, and the Regulation of mRNA Translation in Mammalian Cells
• Chapter 6 Tissue-Specific Regulation of Glucokinase
• Chapter 7 Dietary and Hormonal Regulation of L-Type Pyruvate Kinase Gene Expression
• Chapter 8 Glucose-6-Phosphate Dehydrogenase: Diet and Hormonal Influences on De Novo Enzyme Synthesis
• Chapter 9 Nutritional and Hormonal Regulation of Genes Encoding Enzymes Involved in Fat Synthesis
• Chapter 10 Regulation of Hepatic Gene Expression by Dietary Fats: A Unique Role for Polyunsaturated Fatty Acids
• Chapter 11 Dietary Fat, Gene Expression, and Carcinogenesis
• Chapter 12 Regulation of Acetyl CoA Carboxylase and Gene Expression
• Chapter 13 Apolipoprotein Β mRNA Editing
• Chapter 14 Regulation of the 68 kDa Hepatic Carnitine Palmitoyltransferase
• Chapter 15 Long-Term Regulation of Hepatic Glutaminase and the Urea Cycle Enzymes
• Chapter 16 Effects of Dietary Protein on Gene Expression
• Chapter 17 Vitamin D-Dependent Calcium Binding Protein, Calbindin-D: Regulation of Gene Expression
• Chapter 18 Vitamin D Regulation of Osteoblast Growth and Differentation
• Chapter 19 Retinoic Acid Regulation of Gene Expression in Adipocytes
• Chapter 20 The Role of Vitamin Κ in Clotting Factor Biosynthesis
• Chapter 21 Role of Ascorbate in Regulating the Collagen Pathway
• Chapter 22 Dietary Regulation of Metallothionein Expression
• Chapter 23 Iron-Dependent Regulation of Ferritin Synthesis
• Chapter 24 Vitamin B6 Modulation of Steroid Induced Gene Expression
• Index