Biochemistry of Nutrition - BIOC1305

Biochemistry of Nutrition - BIOC1305

• This course covers the biochemistry of nutrition, exploring topics like nutrigenomics.

Nutrigenomics

• Nutrigenomics examines how nutrition impacts gene expression and health.
• It connects diet to health outcomes.
• This field integrates nutrition, genetics, lifestyle, and health/disease.

Nutrigenetics vs. Nutrigenomics

• Nutrigenetics: Genes influence how your body reacts to food.
• Nutrigenomics: What you eat affects how your genes behave.

Nutrigenetics and Nutrigenomics

• Nutrigenetics studies how genetic differences affect nutrient needs, and dietary impact on health.
• Nutrigenomics studies how food chemicals influence gene expression to affect health.
• Gene expression produces proteins with bodily functions such as nutrition.

Genetic Polymorphisms

• Common gene variants affect how individuals respond to diet and environmental factors, influencing health risks.
• Diet alters cholesterol levels, homocysteine levels and obesity (nutritional component) which differs by genetic component.
• Polymorphisms of apo-proteins, LDL receptor, cholesterol ester transfer protein impact atherosclerosis.
• Polymorphisms of insulin receptor substrate affect type II diabetes.
• Polymorphisms of vitamin D receptor influence susceptibility to osteoporosis.
• Polymorphisms of methylene tetrahydrofolate reductase relate to elevated homocysteine and folate requirement.

Nutrition and Gene Regulation

• Nutrition affects every step from gene activity, protein production and metabolic processes, including signal transduction, and post-translational protein modifications.
• There is a known connection between diet and disease, like cancer, that can be explored by advanced genomic studies.
• Nutrigenomics, transcriptomics (mRNA), metabolomics (cellular processes), and epigenomics (epigenetic modifications) are new technologies for in-depth investigations of nutrition's role in disease.

Nutrients and Gene Expression

• Nutrients mainly alter gene expression through transcription factors, like the nuclear receptor superfamily (48 receptors in humans).
• Many receptors bind nutrients or metabolites (ex: PPAR binds fatty acids, liver X receptor binds cholesterol).
• Receptors (heterodimers with retinoid X receptor) bind specific nucleotide sequences in promoter regions.
• Nutrient binding modifies nuclear receptors' shape, influencing co-repressors and co-activators.
• In metabolically active organs (liver, intestine, adipose tissue), these factors act as nutrient sensors.

Effects of Nutrients on Gene Expression

• Nutrients can interact with genes in three ways: direct, epigenetic, and genetic variations.
• Direct interactions involve nutrients acting as transcription factors, acutely affecting gene expression.
• Epigenetic interactions affect the structure of DNA or histone proteins, leading to chronic changes gene expression.
• Genetic variations involve SNPs (single nucleotide polymorphisms) that modify gene expression and function.

Acute Effects of Nutrients on Gene Transcription

• Certain nutrients act as transcription factors, altering gene expression via specific receptors.
• Examples: Vitamin A with retinoic acid receptors, vitamin D with its receptor, calcium with calcineurin, zinc with metal-responsive transcription factor 1.
• These interactions are short-term signals.

Epigenetics and Nutrition

• Epigenetic effects involve DNA methylation or histone modifications (methylation, acetylation, biotinylation) to impact gene expression.
• These effects are long-lasting and can be heritable.
• DNA methylation, typically at CpG islands, can alter gene transcription and stability.
• Methylation generally silences genes (blocking transcription factors) though rare cases exist where it derepresses genes.
• Methylation is replicated in new cells, making effects permanent.
• Histone modifications affect DNA packaging around histones, influencing gene access and expression.

Histone Modifications

• DNA wraps around histones, which when tightly packed restrict gene access.
• Histone modifications loosen the structure, allowing transcription factors access to gene promoters, activating gene expression.
• Diet influences these epigenetic changes; for example, dietary methyl group availability.

Effect of Carbohydrate on Gene Expression

• High-energy diets lead to obesity and metabolic syndrome.
• Obesity, with reduced overall weight gain, affects mRNA levels of neuropeptides (NPY, AgRP) in the arcuate nucleus (ARC),

Effect of Carbohydrate on Gene Expression (cont.)

• Hyperglycemia increases liver angiotensinogen (AGT) gene expression up to threefold.
• Glucose affects lactase activity and LPH mRNA levels (Lactase/ phlorizin hydrolase)
• Certain carbohydrates might influence LPH gene expression through metabolites.

Glucose Regulated Gene Expression

• Glucose, a key monosaccharide, influences organism's responses to varying nutrient supply.
• In yeast, glucose induces its own metabolism genes and represses alternative carbon source genes.

Glucose Regulated Gene Expression (cont.)

• In mammals, glucose affects insulin synthesis/secretion and liver processes like glucose transport and enzymatic actions.
• DNA sequences and DNA binding complexes affecting glucose-regulated gene expression have been established.

Effect of Dietary Fat on Gene Expression

• Dietary fat is needed for growth and development, beyond energy, impacting membrane lipids.
• Dietary fat modulates gene expression related to metabolism and differentiation in response to fat type/amount.
• Key factors include PPARs, HNF4α, NFKB, and SREBP1c, regulated by direct binding of fatty acids.

Cellular Response to Fatty Acids

• The response to fatty acids depends on quantity, chemistry, and duration.
• Cellular processes, like fatty acid metabolism, receptor levels, and transcription factors, influence the response.
• Regulated processes include carbohydrate and lipid metabolism, cell differentiation, and growth/production of factors (cytokines, adhesion molecules, eicosanoids).

Polyunsaturated fatty acids (PUFA), SREBP-1 and leptin

• PUFAs affect SREBP-1 expression (post-transcription level).
• PUFAs influence SREBP-1 mRNA levels and don't directly reduce leptin mRNA levels but reduction in mature SREBP-1 impacts leptin expression.
• Dietary fatty acid composition can change plasma leptin levels (decreased leptin expression).

Effect of Protein on Gene Expression

• Protein is essential for growth, immunity, and body function.
• Protein function affects gene expression at the macro (bodily functions) and micro (gene level) levels.
• Both protein quality and quantity influence gene expression.
• Intrauterine protein deficiency impacts organs of the newborn.

Insulin Secretion

• Low protein diets reduce pancreatic b-cell mass and insulin secretion response through factors (PKA) and digestive hormones.
• Low protein intake affects insulin biosynthesis related genes.
• Nutritional status significantly impacts genes encoding the insulin-like growth factor system.
• Dietary protein intake connects to decreased cholesterol levels.
• Prolonged low-protein diets reduce essential amino acid plasma levels (ex: leucine and methionine).

Effect of Vitamins on Gene Expression

• Vitamins are crucial micronutrients.
• Mostly, all vitamins are involved in gene expression for the prevention of oxidation of DNA and lipid, and to promote the synthesis of essential proteins/enzymes.
• Vitamin deficiencies impact DNA damage and oxidation.
• Vitamins impact PEPCK and IGF (insulin-like growth factor) gene expression while Biotin is involved in various essential protein synthesis.

Disease Control

• Chronic diseases involve numerous factors acting over time
• (ex: genes, SNPs, environmental factors, behaviors)
• Small effects of genes over time impact on complex disease identification.
• Around 1000 genes cause diseases. Most chronic diseases involve complex interactions between genes and environment.
• Nutrients could influence genes with heightened sensitivity.

Nutrients and Toxicity

• Nutrients, analogous to toxic substances in feed, impact gene expression, possibly exceeding gene level to overcome toxicity effects.
• Nutritional genomics, integrated with genetic data, helps identify individuals at risk/prone to cancer.
• Genome health/nutrigenomics concept deals with how nutritional deficiencies/excess affect genome mutations.

Explore the fascinating field of Biochemistry of Nutrition with a focus on nutrigenomics. This quiz will examine how nutrition impacts gene expression and connects diet to health outcomes. Delve into the differences between nutrigenetics and nutrigenomics while understanding genetic polymorphisms and their influence on health.