Metabolism, Part 2 - Exam #1 Flashcards
Protein composition in the body
- 40% skeletal muscle
- 25% organs
- other contained in skin and blood
How are proteins Catalytic Enzymes?
- Speed up rate of reactions that allow life sustaining bodily reactions to occur;
- Some require coenzymes (B-vits) or cofactors (minerals)
What are the types of Catalytic enzymes?
- Hydrolases – cleave compounds
- Isomerases – transfer atoms in a molecule
- Ligases – (syntheses) join compounds
- Oxidoreductases – transfer electrons
- Transferases – move functional groups
How are proteins Messengers?
Hormones (insulin, glucagon)
How are proteins used Structurally?
contractile, fibrous, globular
How are proteins Immunoprotectors?
- Both innate and adaptive immunity;
- Immunoproteins (AKA immunoglobulins or antibodies) ;
- IgG, IgA, IgM, IgE, and IgD
- Immune Response → Bind to antigens creating an immunoprotein-antigen complex that will be destroyed by reactions with complement proteins or cytokines; destruction also can occur by macrophages and neutrophils through phagocytosis
How are proteins Transporters?
- Carry substances in the blood, in and out of cell through membranes, and within cells;
- Albumin;
- Transthyretin (prealbumin) = complexes with retinal binding protein to transport retinol (Vit. A);
- Transferrin = iron transport;
- Ceruloplasmin = copper transport;
- Lipoproteins - lipid transport;
- Hemoglobin = oxygen/CO2 transport
How are proteins Buffers?
- Acid-base regulation;
- pH too LOW – amino acids ACCEPT hydrogens so pH of solution will increase
- pH too HIGH – amino acids DONATE hydrogens so pH of solution will decrease
How are proteins Fluid Balancers?
- Balance osmotic pressure of blood and tissue by H2O attraction;
- Prevents edema and concentration of fluid within the tissues and maintains it in circulation (Albumin)
What are Conjugated Proteins?
- Protein that functions in interaction with other chemical groups attached by covalent bonds or by weak interactions;
- EX: Glycoproteins
What are Glycoproteins?
- Proteins that contain an oligosaccharides (glycan chain) covalently attached to the polypeptide side-chain through the process of Glycosylation;
- Can be a variety of sugars and proteins;
- Carb as the nonprotein component;
- Typically branched and uncharged
What is Glycosylation that forms glycoproteins?
- Carbohydrate is attached to a hydroxyl or other functional group of another molecule - protein for glycoproteins;
- N-glycosylation – attached at the Amide Nitrogen of the polypeptide side chain
- O-glycosylation – attached at the Hydroxyl Oxygen of the polypeptide side chain
What are Proteoglcyans?
- Class of Glycoproteins with extra carbs;
- Heavily glycosylated proteins;
- Core proteins with many glycosaminoglycan chains;
- High molecular weight;
- Skin, bone, cartilage (connective tissues)
What are Glycosaminoglycans (GAGs) or mycopolysaccharides ?
- Forms of Proteoglycans;
- Long unbranched polysaccharides with repeating disaccharides
What is Primary Protein Structure?
-Sequence of amino acids covalently bound together
What is Secondary Protein Structure?
– 3-D form achieved through HYDROGEN BONDING between amide groups;
- Alpha-helix;
- Beta-conformation or Beta-Pleated Sheet;
- Random coils (least stable)
What is Tertiary Protein Structure?
- Linear, globular, or spherical;
- Affects the shape and function of the type of protein;
- Forms SINGLE polypeptide chains;
- Hydrophobic AA’s cluster toward center;
- Electrostatic (ionic) interactions between the amino acid SIDE CHAINS;
- Strong covalent bonds between Cysteine residues (disulfide bridges)
What is Quaternary Protein Structure?
–Interaction between 2 or more polypeptide chains;
- Oligopolymers (a few monomer units);
- Form multi-unit complexes of polypeptide subunits
- EX: Hemoglobin
What is basic structure of an Amino Acids?
Central Carbon
+ 1 amino (NH2)
+ 1 carboxyl (COOH)
+ R-group side chain (Amino acid specific)
AA’s with Aliphatic Side Chains (non-aromatic)
- Glycine
- Alanine
- Valine
- Leucine
- Isoleucine
AA’s with Hydrolytic Groups (-OH)
- Serine
- Threonine
AA’s with Sulfur Atoms
- Cysteine
- Methionine
AA’s with Acidic groups or their Amides
- Aspartic Acid
- Glutamic Acid
- Asparagine
- Glutamine (may be important for gut health)
AA’s with Basic Groups
- Arginine
- Lysine
- Histidine
AA’s with Aromatic Groups
- Phenylalanine;
- Tyrosine;
- Tryptophan
How else can Amino acids be classified?
- Charge = neutral, negative, positive;
- Polarization = polar neutral, polar charged, non polar neutral, relatively nonpolar
What are Zwitterions?
Overall neutral charge due to the presence of a positive and a negative charge in the molecule
What are NONSESSENTIAL AA’s?
DO NOT need to be consumed, but body can make
What are Conditionally Essential AA’s?
- Must consume an essential AA’s to in order to make those conditionally essential;
- MUST consume during times of GROWTH;
- Or when cannot consume the precursor essential amino acid
What are Essential/Indispensable AA’s?
- MUST consume in the diet; body CANNOT make;
- Phenylalanine (essential) will be used to make Tyrosine (conditionally essential)
- Methionine (essential) will be used to make Cysteine (conditionally essential)
What is the problem associated with PKU?
- CANNOT consume Phenylalanine in the diet, so therefore cannot make Tyrosine;
- So must consume Tyrosine = now becomes essential
What is the basis for Amino Acid SYNTHESIS?
- Focuses on the NONESSENTIAL (the ones the body makes), but if you consume them in high quality protein, your body will not waste the energy to make them;
- Occurs through Transamination
What is needed for Amino Acid synthesis?
-Need the ESSENTIAL Alpha-amino acids’ precursor carbon skeleton (minus the amino group to make a new AA) to synthesize the NONESSENTIAL Amino Acids
What is Transamination?
- The removal of the amino group from the carbon skeleton of the essential and then transfer of the needed amino group to make the new AA;
- EX: Glutamate is produced through transamination of alpha-ketoglutarate and an alpha-amino acid;
What are the 4 truly essential Amino Acids?
- Lysine, Threonine, and maybe Histidine and Tryptophan are truly essential;
- CANNOT be synthesized from precursor carbon-skeletons in the body and must be consumed preformed in the diet;
- Carbon skeletons CANNOT be transaminated
What are Exogenous sources of Protein?
-Sources of proteins are provided in the DIET through animal products (except purified fats) and certain plant products (grains/grain products, legumes, vegetables)
What are Endogenous sources of Protein?
-Sources of proteins are broken down from WITHIN the body → Desquamated
What is the role of enzymes in the utilization of proteins?
- Catalyze the catabolism and digestion of proteins;
- FREE amino acids are then absorbed and utilized by the body for anabolic processes or for energy in times of gluconeogenesis
What is the mechanism for Transamination for amino acid synthesis?
- Alpha-keto acid + Alpha-Amino acid;
- Transaminate (transfer) the AMINO group from the alpha-amino acid to the alpha-keto acid;
- Catalyzed by Aminotransferases
What protein digestion occurs in the MOUTH and ESOPHAGUS?
None, no enzymes present
What proteins digestion occurs in the STOMACH?
- Gastrin (peptide-hormone) released into blood stimulating gastric juices
- HCl denatures proteins and converts pepsinogen to pepsin (active; from parietal cells)
- Pepsin from stomach chief cells hydrolyzes peptide bonds
What protein digestion takes place in the SMALL INTESTINE?
- Partially digested proteins stimulate release of secretin and CCK (hormones)
- Pro-enzymes and bicarbonate (acid neutralizer) are released due to hormones presence
- Pro-enzymes are converted to active enzymes digesting proteins to tri- and dipeptides and free amino acids
What Pancreatic Enzymes play a role in protein digestion?
- Trypsinogen → trypsin (small peptides, some free);
- Chymotrypsinogen → chymotrypsin (small peptides, some free);
- Procarboxypeptidases A & B → carboxypeptidases (free amines);
- Proelastase;
- Collagenase
What are the Brush Border peptidases that aid protein digestion?
- Aminopeptidases, dipeptdylaminopeptidases, tripeptidases
- Tripeptides hydrolyzed or absorbed at brush border
How are peptides/amino acids absorbed in the Brush Border?
- Amino acids transport requires CARRIERS (active or passive)
- EX: Sodium (Na+) dependent transport into cell
How is peptide transport carried out by PEPT1?
- Peptide transport into cells carried out by PEPT1 and the co-movement of protons (H+)
- H+ are pumped back into the lumen in exchange for Na+
- Na+, K+ ATPase pumps Na+ out fo the cell in exchange for K+ to cross the membrane
- Then broken to amino acids
How is there competition for protein carriers?
- There is an overlap and competition for certain carriers between amino acids;
- Not all amino acids have a specific carrier but they are shared;
- Can create deficiency problems if the AA with the higher affinity if consumed in higher amounts
What happens to all Water-Soluble Substances?
- ALL WATER-SOLUBLE substances are transported/diffuse into the portal blood and go to liver;
- This includes amino acids and short-chain fatty acids;
- (Other LIPIDS become chylomicrons and enter the LYMPH)
What is the Lymph?
- Clear fluid that is basically recycled blood plasma;
- Moves directionally toward the heart
What are the Nitrogen-containing NONPROTEIN compounds?
- Glutathione - antioxidant, reacts with H2O2, AA transport, conversion of prostaglandin H2 to D2 & E2
- Carnitine - FA transport
- Creatine - part of phosphocreatine (high-energy compound)
- Carnosine - may be antioxidant
- Choline - methyl donor, part of acetylcholine & lecithin & sphingomyelin
What are Pyrimidines?
Main component of DNA and RNA nucleotide bases;
- 6-membered rings containing N in positions 1 & 3
- Uracil, cytosine & thymidine
- Cytosine → DNA and RNA
- Thymidine → ONLY DNA (=Uracil → RNA)
What are Purines?
Main component of DNA and RNA nuleoctide bases
- 2 fused rings, N in positions 1, 3, 7, 9
- Adenine & guanine → Found in DNA and RNDA
What are the main protein SYNTHESIS hormones?
- ANABOLIC
- Insulin and growth hormone
What are the main protein DEGRADATION hormones?
- CATABOLIC
- Glucagon and stress hormone
What is Deamination?
REMOVAL of amino group
What is Transamination?
TRANSFER of amino group from one AA to AA carbon skeleton or α-keto acid → Catalyzed by aminotransferases
What is the purpose of the Urea Cycle?
- Disposal of ammonia;
- Occurs in the Liver, Urea sent to blood, excreted by the kidney;
- Overall: Amino acids degraded and Arginine synthesized
What is the source of NITROGEN in Urea?
Glutamate
What is the Mechanism of the Urea Cycle?
- NH3, basically from glutamate, combines with CO2 or HCO3- to form carbamoyl phosphate
- Carbamoyl phosphate reacts with ornithine transcarbamoylase (OTC) to form citruline
- Aspartate reacts with citruline to form argininosuccinate
- Arginosuccinate is SPLIT to form fumarate & arginine
- Urea is formed and ornithine is re-formed from cleavage of arginine
How does the TCA and Urea Cycle interact?
-Glutamate combines with products from the point of OAA (TCA cycle) and released CO2 to make Aspartate which then enters the Urea Cycle
What is the normal serum concentration of ammonium?
-20–40μM;
-Increase of serum ammonium to 400μM causes alkalosis and neurotoxicity.
(Alkalosis – reduction of hydrogen ion concentration in arterial blood plasma (pH ~ 7.45) )
What are Aminotransferases?
- Carry out transamination;
- EXCEPT for except threonine and lysine and maybe tryptophan and histidine (TRULY ESSENTIALS)
How is Glutamate degraded to Ammonia?
- Catalyzed by liver glutamate dehydrogenase through oxidative deamination;
- Generates Ammonia and Alpha-Ketoglutarate;
- Produced Ammonia is then used in the Urea Cycle the excreted in urine as NH4+ (Urine pH = 4-8)
How is Glutamate degraded to Glutamine?
-Carried out by glutamine synthase and sent to kidneys where it is sequentially deaminated by glutaminase and then kidney glutamate dehydrogenase
What is Glutamine?
- Major circulatory amino acid;
- Transports ammonia throughout the body (mostly peripheral tissue to kidneys)
- Ammonia when CARRIED in peripheral tissues with does NOT cause alkalosis → non-ionizable form;
- Only free ammonia causes toxicity
What is the role of the LIVER in Glutamate degradation?
- Contains glutamine synthetase (make) an glutaminase (break) in different areas;
- Liver is not a net producer or consumer of Glutamine, but gathers free ammonia NOT in urea
- Duality of enzymes controls how much ammonia is in urea or carried in glutamine
- Urea cycle enzymes are located with glutaminase (break) → leads to excretion
What is the purpose of Urea and Glutamine?
Rid of excess AMINOS → KIDNEY EXCRETION
What happens to the amino group from lysine, threonine, tryptophan and histidine?:
- Intermediates of their metabolism (NOT by TRANSAMINATION) can then be converted to glutamates, which will then ultimately undergo transamination to ammonia and turn into urea and the excess aminos excreted;
- Threonine = to Glycine then transaminated;
- Lysine;
- Tryptophan;
- Histdine = through glutamate to urea or glutamine
What is produced by the metabolism of the carbon skeleton or alpha-keto acid from protein catabolism?
- Energy
- Glucose and ketones
- Cholesterol
- Fatty acids
What are the Branched Chain Fatty Acids?
- Leucine, Isoleucine, and Valine;
- Catabolized/oxidized to corresponding alpha-keto acids for fuel in the extrahepatic tissues of the muscle, adipose, kidney and brain;
- These tissues contain aminotransferases NOT in the liver;
- Increased metabolism of BCAA’s during exercise for energy!
How are BCAA’s catabolized in extrahepatic tissues>
First two enzymes are the same for all 3 =
- Branched-chain aminotransferase then,
- Branched-chain alpha-keto acid dehydrogenase complex (analogous to pyruvate and alpha-ketoglutarate complexes and requires the same 5 cofactors);
- These are then followed by Acyl-CoA derivatives
How is Leucine (BCAA) degraded for energy?
- Acetoacetyl-CoA → (Acetyl-CoA → TCA ) OR Ketone Bodies
- Acetyl-CoA → TCA
How is Isoleucine (BCAA) degraded for energy?
- Acetyl-CoA → TCA
- Succinyl-CoA → TCA
How id Valine (BCAA) degraded for energy?
→ Succinyl-CoA → TCA
What is the Glucose-Alanine cycle?
- Alanine (amino acid) carries ammonia and carbon skeleton of pyruvate from MUSCLE PROTEIN BREAKDOWN to the LIVER
- Ammonia → Excreted;
- Pyruvate → Glucose → Energy goes back to the muscle
What is the mechanism of the Glucose-Alanine cycle?
- Pyruvate from glycolysis in muscle takes NH4+ from glutamate to make Alanine (alanine aminotransferase);
- Alanine travels through the blood to the liver;
- Liver (alanine animotransferase) removes NH4+ from Alanine and combines it with Alpha-ketoglutarate;
- Regenerates Pyruvate (back to gluconeogenesis) and Glutamate;
- Glutamate goes to urea cycle and excretes NH4+
Amino Acids (dietary or endogenous protein) can be used to MAKE ….
- Biogenic amines
- Peptide hormones
- Plasma proteins
- Structural Proteins
- Enzymes
- Immunoproteins
- Transport proteins
What are amino acids composed of?
Amino Group + Carbon Skeleton (alpha-keto acid)
What happens to extra amino groups?
Amino group → Urea Ammonia → Excretion by kidney (most) or intestine (trace)
What can the carbon skeleton be used for?
- Energy + CO2 or,
- Glucose/ketones or,
- Fatty acids
How can tissue proteins go through CATABOLISM?
-Cellular proteins can be degraded by either …
=Lysosomal
=Proteasomal
=Calcium/calcium-activated proteolytic degradation;
-Yields Amino Acids to synthesize other bodily compounds
What are High Quality/Complete Proteins?
Supplies ALL the essential amino acids in adequate amounts
EX: Animal products
What are Low Quality/Incomplete Proteins?
-Low in one or more of the essential amino acids and require complementation to adequately supply the diet of needed amino acids;
-Missing/low content amino acid is know as the “Limiting Amino Acid”
-EX: Wheat, rice, other grains → Low in Lysine, threonine (some) and tryptophan (some)
-EX: Legumes → Low in Methionine
=Grain + Legume = Complement Complete Protein Source
What is Protein QUALITY based on?
- Nitrogen balance or status
- Chemical or Amino Acid Score
- Protein digestibility corrected amino acid score
What is the RDA for protein?
- RDA Adults = 0.8 k/kg → Based on ESSENTIAL Amino Acids
- NO difference in RDA for athletes
- No UL currently sited for protein intake
- AMDR = 10-35% of total kcal intake
What is Kwashiorkor?
Adequate kcals, but NOT enough PROTEIN → Edema (water retention) due to lack of blood proteins balancing osmotic pressure in tissues
What is Marasmus?
Wasting, emaciation from chronic insufficiency of kcals AND protein
What is Nutritional Genomics (Nutrigenomics)?
“the field of study concerned with complex interaction among genes and environmental factors”;
Fueled by research such as the Human Genome Project
What is Nutrigenetics?
- “concerned with the effects of gene variations (also called gene variants) on the organism’s functional ability, specifically its ability to digest, absorb, and use food to sustain life”;
- Genes AFFECTING foods;
What is Nutrigenomics?
- “concerned with how bioactive components within food affect gene expression and function;
- Food AFFECTING genes
What is Pharmacogenomics?
- Studying dealing with how genes interact with pharmaceutical drugs;
- More advanced and easier to research due to controlled composition of the drugs
What might be an effect of various alleles on drug use?
-People potentially catabolize drugs at different rates, therefore changing the dose that they would require
What do various alleles have on Vitamin K Epoxide Reductase Complex and coagulation?
- Vitamin K Epoxide Reductase Complex subunit 1 (VKORC1) enzyme recycles reduced Vitamin K and promotes blood clotting through its association with Vitamin K-dependent coagulation factors;
- Different alleles between people might cause them to require higher or lower doses of anticoagulants to act on VKORC1 to prevent clots
What are the Advantages of Pharmacogeneomics?
- Prior research in drugs and metabolism
- Usually only a single, purified compound with a defined chemical make-up
What is the main disadvantage of Nutrigenomics?
-Foods contain so many various compounds in such varying amounts its hard to be totally sure of an outcome
What is mostly studied in Nutrigenetics?
-single gene disorders – INBORN errors of metabolism caused by a mutation (different allele in the gene) with different degrees of rarity
What are Single Nucleotide Polymorphisms (SNPs)?
- Single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population;
- Changes the function or causes loss of protein function;
- -Some mutations or subtle variations only slightly effect protein function and only may increase/decrease potential risk of disease;
- Sometimes might even pose a benefit
- EX: PKU;
- EX: Familial dyslipidemias
What are most diseases?
- Multifactorial = meaning a combo of gene changes are the cause
- EX: Obesity – usually seen as multifactorial, but some studies have shown people who don’t make leptin or have a defective receptor, melanocortin-4
What are Nutrition/Lifestyle changes NOT likely to have an effect on?
- Highly penetrant SINGLE GENE disorders especially the homozygous individuals;
- Heterozygous would be more responsive
How do GENES factor into disease risk?
may give you greater/lesser risk of disease development
How does Diet/Lifestyle factor into disease risk?
nutrition and lifestyle choices greatly affect your risk of disease and can also factor into or act on the tendency found within the inherited genes in developing nutrition-related diseases
What is the Folate genetic variation for SNP 667>T?
- Genetic variation = SNP 677C>T in the gene for 5,10-methylenetetrahydrofolate reductase (MTHFR)
- Frequency of T-homozygosity = 1% or less among Blacks to 20% or more among Italians and Hispanics
- Result of variation = WITH SNP have problems when consume less than adequate folate and might actually REQUIRE MORE
- Disease risks = colon cancer, fetal neural tube defects, and CVD
What effect can genome variation have on nutrient utilization?
- Variant in genome can alter how the nutrient is handled and can affect the requirement or increase/decrease sensitivity;
- Folate example
What are the protein genes associated with lipids receptors?
- APOE (apoprotein E) = IDLs
- APOA1 (apoprotein A1) = HDL
- CETP (cholesterol ester transport protein)
What are the common allele variations for APOE?
–E2, E3, E4 Possible Genotypes = each gives a different response to diet/lifestyle changes •E2/E2, E2/E3, E2/E4 •E3/E3, E3/E4 •E4/E4
For APOE, those with at least ONE E4…
- Highest basal levels of lipids and respond BEST to low fat diets to lower lipid levels;
- But DON’T respond to soluble fiber to lower or exercise to higher HDLs
- Fish Oil Supps. = increase serum cholesterol
- Alcohol and Smoking = increases LDL and increases carotid artery intima-media thickening which enhances risk of atherosclerosis (around age 40)
For APOE, those with ONE or MORE E2…
- Low LDL cholesterols, but high triglycerides and respond to soluble fibers, fish oil, and exercise to increase HDL;
- But DO NOT responds to low fat diets
For APOA1, what variant change in women due to diet intervention?
- 75G>A ;
- Women with 2 G alleles HDL levels drop with increased polyunsaturated fat intake → better response to monounsaturated
- Women with A allele (2 is best) increase HDL with increase polyunsaturated intake and EVEN BETTER with mono-’s than those with G
What changes does Nutrigenetics deal with?
deals with DNA differences that cause changes in the protein made that alters nutrition requirements
What other field does Nutrigenomics overlap?
-Enters the field of epigenetic and short-term gene regulation or expression as brought about by nutrient intake
How can knowing a person’s genotype aid nutrition intervention?
- Knowing a particular persons genotype and the mechanism of the nutrient affect could yield much more effective and specific nutritional interventions!
- EX: Omega-3 fatty acids can reduce inflammation through genes → Meaning knowing the genotype can have diet
What is Epigenetics?
- Changes in gene expression that does NOT involve any change in the actual DNA sequence;
- Information is passed through generations, but without being encoded;
- Expression passes from parent to daughter cells during cell division, and sometimes parent to offspring
How do Epigenetic changes occur?
Changes in expression due to covalent modification of histones and/or the location of histone variants
What are Histones?
- Highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes;
- The chief protein components of chromatin, acting as spools around which DNA winds, and play a role in gene regulation;
- Condenses the long strands of DNA
Does the in utero environment contribute to adult health?
- In utero (in the womb) environment has shown a great contributor to health and susceptibility in a adulthood
- EX: Deprivation in the womb, might lend someone to obesity and T2DM due to overindulgence to counter having one been deprived
What are Paramutations?
- Gene expression passed from cell to daughter cell, but NOT parents to child
- EX: X-inactivation and imprinting – Only ONE allele of two being expressed
What is DNA methylation?
- Adds a methyl to the Cytosine/Adenine DNA nucleotide;
- When methylated strands of DNA are replicated, initially they are produced unmethylated.;
- But, DNMT1 DNA methylase will specifically methylate the new strand and maintain the DNA methylation expressed in the daughter sequences;
- DNMT! makes methylation irreversible! and alters gene expression
What is Histone Modification?
- Epigenetic gene variation;
- SHORT-TERM, not inherited, and regulate gene expression
What might control Epigenetic memory?
- Might be dependent upon polycomb groups of proteins;
- Humans have at least two polycomb-group repressive complexes = PRC1 and PRC2;
- They methylate H3K27 in target genes.
How do Polycomb -groups control histones and gene expression?
have the ability to remodel chromatin and so that epigenetic silencing will occur and turn off gene expression
What are the variants of Histones?
- H3, H2A and H2B;
- Active, expressed genes have histones H3 and H2A replaced by variants H3.3 and H2AZ
What is HFD?
-Histone-fold domain = structural area common to all core histones
How are histones modified?
- TYPICALLY single and specific, but some sites will undergo more than one type;
- Individual function is associated with these changes;
- N-terminal tails of H3 and H4 have many sites of modification
What are the types of modifications for the N-terminal of H3 and and H4?
- Methylation
- Acetylation
- Phosphorylation
- EX: ACETYLATION of H3 and H4 = ACTIVE chromatin while METHYLATION = INACTIVE chromatin;
- EX: Arg residue methylation and Ser phosphorylation
What is the histone modifciation nomenclature?
- TYPE of HISTONE, one-letter AA code, and position of the residue counting from the N-terminal
- Ac – acetylation
- Me – methylation
- Ph – phosphorylation
- Ub – ubiquitylation
- Su – sumolaytion
What are the functions of Euchromatin and Heterochromatin?
- gene expression, gene repression and DNA transcription;
- different types of histone modifications occur at the different states
What is Euchromatin?
-Nucleosomes are loosely packed w/ nucleosome-free regions that can bind regulatory proteins; Active; replicate in the early stages of the cell cycle
What is Heterochromatin?
-Nucleosomes are densely packed and associated with heterochromatin protein 1 (HP1); “gene poor” w/ much repetitious DNA and replicates in late S phase of cell cycle (gene-poor = non-coding regions)
What are some nutrients required for gene expression?
- Resistant Starch → Butyrate
- Folate and choline → Methyl group transfers
- Vitamins A and D (and many others) → Bind to binding proteins that function as transcription factors
What is Transcription of proteins?
DNA → mRNA;
-mRNA – coding RNA, meaning it is TRANSCRIBED into protein
What are miRNA and siRNA?
NON-CODING RNAs that compose RNA interference or RNAi
What is miRNA?
(microRNA) which functions in transcriptional and post-transcriptional regulation of gene expression;
- Function via base-pairing with complementary sequences within mRNA molecules
- Results in gene SILENCING via translational repression or target degradation
What is siRNA?
(silencing RNA) acts in the RNA interference (RNAi) pathway;
-Interferes with the expression of specific genes with complementary nucleotide sequence
What is Translation of proteins?
mRNA → Protein
What is Post-translation modification>
Protein → Modified Protein
How can miRNA prevent translation of proteins?
- Directly – by hybridizing to it mRNA
- Indirectly – by hybridizing to mRNA for transcription factors for one or more earlier transcription of the final protein
- Inhibitor – miRNA promotes inhibition of an inhibitor by preventing its mRNA from being translated to protein
What are the steps of gene expression that can be regulated?
- Open DNA so transcription “machinery” can reach the gene to be transcribed
- Transcription of transcription factors, other activators, and repressors/inhibitors
- Reading the gene
- Transcribing the gene
- Make mRNA
- miRNA prevents mRNA genes directly or indirectly; or promotes inhibition of an inhibitor
- Regulate ribosomal function and tRNA
- Regulate post-translational modification
What is the potential for nutritional genomics?
- Bioactive foods components;
- Functional foods;
- Dietary supps. for specified genotypes
