Genetic Variations & Metabolism


Section 1.1: Metabolism Overview

Human metabolism is the sum of all chemical transformations taking place within our body to keep our cells alive. The chemical transformation of molecules within the cell require certain protein catalysts called enzymes that facilitate these biochemical reactions. Within metabolism, biochemical reactions can be either anabolic or catabolic. Anabolic pathways include reactions that require energy and result in the synthesis of new macromolecules while catabolic pathways require the breakdown of complex macromolecules and result in the release of energy. (O’Connor, et al 2010) The end products produced from these pathways are known as metabolites and it is crucial for the cell to control the level of critical metabolites by balancing the rates of the catabolic and anabolic pathways. These metabolites perform crucial functions within the cell and are critical in determining our expressed human phenotype.



Figure 1.1: Metabolism Simplified

All food is composed of nutrients which our body requires to function optimally. The food we eat is digested within the alimentary tract and broken down into its nutrients. These nutrients are then absorbed by the bloodstream and sent to cells and tissues which will transform them into energy and a variety of metabolites. (Poian et al. 2010) Each nutrient has unique properties that allow it to be utilized for a variety of functions within the body once metabolized. Nutrition plays a crucial role our health since pathways in our body require certain nutrients to function. Nutrients can either be macronutrients or micronutrients, each of which are crucial in the cellular function.

Section 1.1.1: Macronutrients        

Macronutrients are nutrients that the body requires in large amounts and are broken down to release energy. The amount of energy these macronutrients can potentially produce is measured in calories. Not all macronutrients consumed are utilized by the cells for energy and the unutilized macronutrients are stored as muscle or fat. The number of calories consumed must be equivalent to the number of calories burned through physical energy exertion to prevent weight gain or weight loss. (USA 2010) There are three types of macronutrients from which these calories can be consumed from and they include carbohydrates, fats and proteins. The Food and Nutrition Board (FNB) recommends that the average adult should have a diet consisting of 45-65% carbohydrates, 20-35% fat and 10-35% protein. (Institute of Medicine 2005) Each of these macronutrients has unique functions within the body and their consumption ratio should be tailored to an individual’s phenotype, genotype and energy exertion to achieve optimal health. (Aus.Gov 2016)

Dietary carbohydrates provide the main source of fuel for our body and is therefore required in the highest quantity amongst the macronutrients. Carbohydrates consist of sugars, starches and fibers, all of which are metabolized via direct oxidation in various tissues or through glycogen synthesis within the liver and muscle tissues. Glucose is typically the metabolite for these pathways and it is required by many cells and organs such as the brain to obtain energy for proper function. (Jequier 1994)

Dietary proteins are important for a variety of functions within the body once metabolised. Proteins are broken down into amino acids which can then be used as building blocks to manufacture and repair functioning proteins (enzymes, hormones, tissues etc.) or they can be consumed as an energy source for the cells. (WSU 2016)

Dietary fats play an important role within the body and release over double the amount of energy once metabolised (9 kcal/gram) in comparison to proteins and carbohydrates (4 kcal/ gram). 8 Fats are broken down into lipids which can be utilized for fat soluble vitamin transport, insulation and as an energy reserve. The types of fat include saturated, unsaturated and trans-fat, all of which are vary based on the bonds between lipid molecules which effect the rate at which they are broken down by the human body. (Opchart 2003)

Section 1.1.2: Micronutrients         

Micronutrients are nutrients required by our cells in trace amounts that enable proper function of cells. There are a variety of micronutrients present within the food we consume and these micronutrients are metabolised and released into our blood stream to aide in bodily functions. (Shenkin 2006) The main categories of micronutrients include water-soluble vitamins, fat-soluble vitamins, major minerals, electrolytes, essential trace minerals, non-essential trace minerals and water. An adequate intake of micronutrients is necessary for optimal human health, however there is a limit to consumption of each micronutrient. Researchers have developed a recommended daily allowance (RDA) to ensure adequate consumption for each micronutrient within our diet. Micronutrient deficiencies are common in third world countries and lead to a variety of health disorders in those malnourished individuals. (WHO 2016) Since there is a lack of access to food with nutritional sustenance in these areas, it is difficult for individuals to reach adequate levels of certain micronutrients.

Micronutrient deficiencies are also very common in the western world where poor dietary choices are resulting in deficiencies of key nutrients. For instance, studies have shown that 32% of Canadians have below adequate levels of circulating vitamin D. (CAN.Gov) This is only one example of how prevalent micronutrient deficiency is across the globe. Like macronutrients, the amount of each micronutrient consumed daily should be tailored to an individual’s energy exertion, phenotype and most importantly their genotype.


Water Soluble Vitamins Fat Soluble Vitamins Major Minerals Electrolytes Essential Trace Minerals Nonessential Trace Minerals
Vitamin C (Ascorbic Acid) Vitamin A Calcium Sodium Iron Fluoride
Vitamin B1 (Thiamin) Vitamin D Phosphorus Potassium Zinc Arsenic
Vitamin B2 (Riboflavin) Vitamin E Magnesium Chloride Copper Boron
Vitamin B3 (Niacin) Vitamin K     Selenium Nickel
Vitamin B5 (Pantothenic Acid)       Chromium Silicon
Vitamin B6 (Pyridoxine)       Iodine Vanadium
Vitamin B7 (Biotin)       Manganese Cobalt
Vitamin B9 (Folic Acid)       Molybdenum  
Vitamin B12 (Methyl Cobalamin)          

Table 1.1: Micronutrients relevant to human nutrition and metabolism 

Section 1.2 – Metabolic Pathway Regulation        

A metabolic pathway is a series of enzyme-mediated biochemical reactions that can either be anabolic or catabolic. Important metabolic pathways include Glycolysis and the Krebs Cycle, both of which produce metabolites that are crucial to sustaining cell life. (Nature 2016) The rate of reactions within metabolic pathways are altered to meet the nutritional and biochemical demands of the body. Metabolic pathway regulation is the way in which the cell can control the rate of the reactions within the cell to maintain homeostasis. There are four common mechanisms that cells use to regulate metabolism and they include modulation of allosteric enzymes, hormonal activation by covalent modification or induction of certain enzymes, directional shifts in reversible reactions and translocation of enzymes within the cell. These four mechanisms that control metabolism are dictated by the expression of genes coding for the relevant enzymes involved in the pathway and the relative concentration of each product and reactant. (Berkhout et al. 2013)

Section 1.2.1 – Gene Expression     

Gene expression is a term used to describe the coding of proteins from genes. The first step in gene expression is transcription, in which a segment of DNA is copied into RNA by RNA polymerase. (Clancy 2008) The segment of DNA that is copied is from the coding region of the gene (exon) as opposed to the non-coding region (intron). (Conti et al. 2012) The mRNA that is produced during transcription undergoes the second step in the gene expression process which is translation. During translation, the mRNA containing the genetic information from the original DNA template is read by the ribosome within the cell. mRNA is comprised of a sequence of nucleotides and a group of three adjacent nucleotides is considered a codon. One amino acid is brought to the ribosome for its corresponding codon and the sequence of codons is read until a chain of linked amino acids is created. This chain of amino acids then undergoes necessary modifications and the final product is a protein. (Clancy 2008)



Figure 1.2: Process of gene expression from a DNA template to the final protein

The process of gene expression is regulated by the cells external environment and stimuli. (Hoopes 2008) Within the context of nutrition, genes will be expressed for enzymes involved in the metabolism of available nutrients. Nutrients can also act as co-factors for enzymes that can aide in their function within the cell, so their presence will also induce the production of that enzyme. Since the metabolism of nutrients is crucial to cell life, it is equally important that the genetic blueprint for these proteins is reliable. As humans, we vary on a genetic level and thus our metabolic pathways do not always function optimally. (Illig et al. 2010)


Figure 1.3: Codons and their corresponding amino acids

Section 1.2.2 – Single Nucleotide Polymorphisms

Single nucleotide polymorphisms (SNPs) are the most common genetic variation among the human population. As the name suggests, an SNP is a single nucleotide change within a gene sequence. If more then 1% of the population caries a different nucleotide at a certain position, then that variation is classified as an SNP. (Scitable 2016) On average, SNPs occur once every 300 nucleotides which equates to an estimated 10,000,000 SNPs within the human genome. (NIH 2016) These SNPs occurring throughout the intron and exon regions of genes with the majority falling within the intron region. (Scitable 2016) SNPs that reside within the exon region of a gene can either be synonymous or nonsynonymous. Synonymous SNPs (sSNPs) are commonly referred to as silent mutations and do not influence the synthesis of proteins. (Hunt 2014) Nonsynonymous SNPs (nsSNPs) are commonly referred to as missense mutations and they influence the synthesis of proteins changing the structure of the codon to represent a different amino acid. The 1000 Genomes Project discovered that the average person carries 250 to 300 non-synonymous SNPs with 50 to 100 variants previously implicated in inherited disorders. (Durbin 2010)  New fields of genetics are now emerging and conducting research on how these SNPs impact our health and our metabolism.



Figure 1.4: Structure of DNA when a non-synonymous SNP is present(NIH 2016)

Section 1.3 – Nutrigenomics & Nutrient Deficiencies      

Nutrigenomics is the field of study that works to determine how SNPs in the human genome result in distinct nutritional requirements. There are many SNPs that impact metabolic pathways for a variety of nutrients. (NIH 2016) These SNPs effect the structure of certain enzymes that often result in an loss of function for the enzyme to effectively metabolize nutrients. The result of an inability to metabolize certain nutrients is nutrient deficiency. Even though an individual may be eating the RDA for a certain nutrient, their body may not be metabolizing all those nutrient due to SNPs, thus resulting in a nutrient deficiency. There are many genes that play an important role in metabolism whose SNPs are prevalent and negatively impact the metabolism within the cell.

Report Written By: Cole Kirschner




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