Protein synthesis, nutrition and genetics

FNN200

Process fo creating polypeptides

• start with DNA

• Transcription into RNA

• translation using a ribosome in the nucleus to turn the mRNA into a polypeptide chain 

• errors in this will result in the wrong protein being made

Gene expression regulation

• each stage is carefully regulated and not all genes are expressed in all cells at all times

  • tissue specific control of expression

• All cells have the same DNA but differences come from what part of it is expressed

Factors that affect gene expression and protein synthesis

• limiting amino acids

  • protein quality

  • specific AAs (Leucine for muscles)

• Energy state of the body

  • feeding/fasting

  • growth/pregnancy

  • illness

  • exercise

  • hormones (insulin → anabolic, glucagon + epi + cortisol → catabolic)

• Diet

  • vitamins and minterals can impact transcription and translation 

  • macronutritns bind DNA binding elements

• Errors in DNA

  • Inborn errors of metabolism

  • single gene disorders 

• Genetic alterations 

  • Epigenetic changes

  • Single-nucleotide polymorphisms (SNPs)

Diet and genes

• both regulate one another

• nutrients regulate gene expression 

• genetic variation changes the response to nutrients 

Lipid regulation of gene expression 

• PPAR

• Fatty acid compounds activate receptors 

  • also Eicosanoids 

• Target genes: 

  • lipid and glucose metabolism 

• Activation of the PPAR complex directly activates the genes 

Carbohydrate regulation of gene expression

• Regulate transcription of lipogenic genes through ChREBP

  • Via glucose 

• Forms a phosphatase that removes a phosphate and throguh this acts on genes

• Target:

  • alters the expression of genes involved in glucose and lipid metabolism

ChREBP

• carbohydrate response element binding protein 

Epigenetics from video

• molecules activate and deactivate genes 

• Proteins determine cell behaviour 

• chemical tags on genes turn them on or off

  • methyl off 

• cell division in some and some is deactivated 

Genome

• contains all information necessary to create cells we are composed of 

• permanent and identical between cells 

Epigenome

• second genome

• set of chemical switches that interact with DNA and affect how genes are expressed 

• do not change the DNA sequence 

  • is reversible 

• can be transfered throguh generations

Epigenetics meaning

• above the genome 

Methylation

• represses gene expression

• addition of methyl group blocks transcription 

  • without this there is no translation and therefore no protein synthesis 

Histones

• proteins around which DNA coils

Histone methylation 

• inhibits transcription

Histone acetylation

• unwinds the DNA → increases transcription

Histone de-acetylation

• removes acetyl groups causing DNA to wind more tight and supresses the genes

Epigenetic modification can be stable and inherited

• Nutrition, smoking, sedentary, alcohol, ionizing, stress 

• can lead to inherited metabolic disorders

Epigenetics and aging 

• changes occur in the lifespan which affect disease susceptibility 

• Not fully deterministic 

• you can change through life 

Examples of epigenetic changes

• exercise training changes epigenome of skeletal muscle 

• increases methylation of specific genes whcih are associated with inflammatory processes 

• Decreased methylation of genes involved in mitochondrial biogenesis 

  • more gene expressed → more glut4 → more training = more glut 4 

Study about conception 

• cold induced epigenetic programming of sperm producing more brown adipose in offspring 

  • how does conception month change adipose tissues 

• Looked at when babies were conceived if it was cold or warm

• those with cold had more brown fat than those who were concieved in warm

Mice study on temperature of conception

• in cold temperatures 

  • more active BAT 

  • epigenetic changes in the sperm of the father so it was happenign independently of the mother 

  • more resistant to obesity 

Main takaways about brown adipose and sperm study

• Epigenetic changes from parents environmental exposures can be inherited 

• could affect health outcomes such as risk of metabolic disease and obesity

• unsure if it would impact multiple generations in humans 

Diseases and epigenetics

• Environmental

  • cells epigenetic markers can change throguh environmental exposures and DNA may repaid genes or have incorrect mylenation 

  • lead to altered phenotype 

• Genetic

  • DNA sequence in variation

  • many cancers have genetic mutations which cause the cancer but this can also be impacted by the environment

Personlaized medicine

• personalized treatments based on individuals unique DNA profile 

  • personalized chemo based on DNA profile of the tumor 

• may not be the same for all individuals 

Nutrigenetics

• study of how genetic variability between people affects individual metabolism of nutrients and subsequent health outcomes 

• How genes respond to food 

  • preferences 

  • variants in some genes change how people respond to glucose increasing how much sweets they eat 

Nutrigenomics

• how food affects how your genes behave

• nutrients bind to transcription factors and affect protein synthesis

• Epigenetics

  • not changing sequence just what is expressed

Modifier genes

• small genetic variations that changehow we respond to dietary factors 

• differ from mutations in genes directly associated with a disease 

• SNPs that actually show effects in the body 

INdividual responses to nutrients

• if you have 3 genotypes 

• a dietary factor leading to health outcomes may have 

  • increase in genotype A 

  • decrease in genotype B or

  • No effect in genotype c 

• leads to differences in study results because of different dietary impacts 

Coffee and Cardiovascular disease

• different genotypes lead to different responses 

• those who have a faster metabolism are more likely to have decreased risk of CVD from coffee

• people with the genotype for faster metabolism probably have an increased risk of CVD from coffee 

Genetic variation responsible for the coffee CVD

• CYP1A2

• this gene changes how fast you metabolize coffee based on different snps 

Personalized nutrition

• tailorign dietary advice and interventions to accommodate an individuals unique factors like genetics, health condition, lifestyle patterns, personal preferences 

  • looking at individual specifics