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Human Nutrition Flashcards

Human Nutrition

Essential and Nonessential Amino Acids

  • Essential Amino Acids: These must be obtained from the diet.
    • Histidine
    • Isoleucine
    • Leucine
    • Lysine
    • Methionine
    • Phenylalanine
    • Threonine
    • Tryptophan
    • Valine
  • Nonessential Amino Acids: The body can synthesize these.
    • Alanine
    • Arginine
    • Asparagine
    • Aspartic acid
    • Cysteine
    • Glutamic acid
    • Glutamine
    • Glycine
    • Proline
    • Serine
    • Tyrosine
  • Branched Chain Amino Acids (BCAA): Isoleucine, leucine, and valine.
  • Vegans and vegetarians need to be particularly mindful of obtaining all essential amino acids through their diet.

Digestion of Proteins

  • Proteins are broken down into smaller compounds for absorption.
  • Digestion primarily occurs in the stomach and small intestine.
  • Minimal digestion in the mouth and esophagus.

Stomach

  • Parietal cells secrete HCl, maintaining an acidic environment for proteolytic enzymes.
  • Pepsinogen (inactive enzyme) is converted to pepsin (active enzyme) in the presence of HCl. Pepsinogen is a pro-enzyme, also called a zymogen.
  • HCl denatures proteins, exposing them to proteases.
  • Pepsin cleaves peptide bonds adjacent to the carboxy end of amino acids like leucine, methionine, aromatic amino acids (phenylalanine, tryptophan, tyrosine), glutamate, and aspartate.
  • Pepsin accounts for approximately 10-20% of protein digestion, producing free amino acids, oligopeptides, and large peptides.

Small Intestine

  • Chyme entering the duodenum stimulates the release of secretin and CCK from mucosal endocrine cells.
  • These hormones stimulate the pancreas to secrete alkaline pancreatic juice, bicarbonate, electrolytes, water, and zymogens (inactive enzymes).
  • Brunner's glands release mucus-rich secretions, neutralizing chyme acidity and preparing the environment for further digestion.

Pancreatic Zymogens

  • Trypsinogen
  • Chymotrypsinogen
  • Procarboxypeptidases A and B
  • Trypsinogen activation occurs only in the small intestine to prevent organ damage.
  • The pancreas produces a trypsin inhibitor for protection.
  • Enterocytes secrete enteropeptidase (formerly enterokinase), converting trypsinogen into trypsin.
  • Trypsin then activates chymotrypsinogen into chymotrypsin and procarboxypeptidases into carboxypeptidases.
  • This cascade ensures protease activation occurs only in the small intestine.

Enzyme Specificity

  • Trypsin cleaves peptide bonds at the carboxy end of basic amino acids (lysine and arginine).
  • Chymotrypsin targets peptide bonds at the carboxy end of aromatic amino acids (phenylalanine, tyrosine, tryptophan) and those adjacent to methionine, asparagine, and histidine.
  • Carboxypeptidases are zinc-dependent proteases.
    • Carboxypeptidase A hydrolyzes peptides with C-terminal aromatic or aliphatic neutral amino acids.
    • Carboxypeptidase B cleaves basic amino acids from the C-terminal end.
  • Enteropeptidase:
    Trypsinogen \rightarrow Trypsin
  • Trypsin:
    Chymotrypsinogen \rightarrow Chymotrypsin
  • Trypsin
    Procarboxypeptidases \rightarrow Carboxypeptidases

Enterocyte Peptidases

  • Enterocytes produce aminopeptidases, dipeptidylaminopeptidases, and tripeptidases.
  • Aminopeptidases cleave amino acids from the amino (N)-terminal end of oligopeptides.
  • Dipeptidyl aminopeptidases are magnesium-dependent and cleave dipeptides.
  • Tripeptidases hydrolyze tripeptides into dipeptides and a free amino acid.
  • Some tripeptides (e.g., triglycine and proline-containing peptides) are absorbed intact by enterocytes and then hydrolyzed intracellularly.

Absorption of Peptides and Amino Acids

  • Most amino acids are absorbed in the duodenum and upper jejunum, but absorption can occur throughout the small intestine.
  • Enterocytes have carriers/transporters for amino acids to cross the brush border and basolateral membranes.

Amino Acid Transport Systems

  • Transporters vary in mechanism: passive (exchangers or uniporters) and active (driven by transmembrane gradients).
  • Most amino acids are carried across the brush border membrane via sodium-dependent transporters.
  • Sodium first binds to the carrier, increasing its affinity for amino acids, or vice versa.
  • The sodium-amino-acid-transporter complex undergoes a conformational change, delivering sodium and amino acids into the enterocyte cytosol.
  • The Na^+/K^+-ATPase pump then moves sodium out of the cell.

Factors Affecting Affinity

  • Hydrocarbon side chain size and net electrical charge affect carrier affinity.
  • Larger side chains have higher affinity.
  • BCAAs (valine, leucine, isoleucine) and methionine are absorbed fastest.
  • Essential amino acids are absorbed faster than non-essential ones.
  • Neutral amino acids are absorbed faster than basic or acidic amino acids. Glutamate and aspartate (acidic, non-essential) are absorbed slowest.
  • Competition for transporters can occur; large amounts of one amino acid may affect the absorption of others.
  • Imbalances due to supplements can disrupt normal intracellular amino acid supply and negatively affect protein synthesis.
  • Amino acid supplements can be expensive and cause gastrointestinal problems.

Peptide Transport

  • Peptides are transported more rapidly than free amino acids.
  • Di- and tripeptides are transported via the peptide transporter 1 (PEPT1) system, involving movement across the brush border membrane with protons (H^+).
  • This causes depolarization of the apical membrane and influx of di- and tripeptides and H^+ into the enterocyte, lowering intracellular pH.
  • H^+ is pumped back out in exchange for Na^+ to prevent further acidification.
  • The Na^+/K^+-ATPase pump maintains the ionic gradient.
  • Inside the enterocyte, peptides are hydrolyzed by cytosolic peptidases into free amino acids, but some may escape and enter the bloodstream intact.
  • Intact peptides in the bloodstream can cause illnesses like inflammatory bowel disease or celiac disease.

Transport to Bloodstream

  • Amino acids must be transported across the basolateral membrane of enterocytes into the interstitial fluid.
  • This is accomplished by sodium-dependent amino acid transporters.
  • Amino acids enter the blood through capillaries draining to the portal vein towards the liver.
  • Extra-intestinal tissues uptake amino acids via similar transporters.
  • The sodium-dependent N system is prominent in the liver.
  • The liver monitors absorbed amino acids and adjusts metabolism accordingly.
  • After a meal, the liver takes up 50-65% of amino acids (mostly non-essential) from the portal vein for its metabolism.
  • BCAAs are spared by the liver and used by other tissues like skeletal muscles, kidneys, and the heart.
  • The liver derives up to 50% of its energy from amino acid oxidation, largely for gluconeogenesis or urea synthesis.
  • In the fasted state, the liver produces glucose from non-carbohydrate sources (gluconeogenesis), with amino acids as a major substrate.
  • Glucagon and glucocorticoids promote hepatic gluconeogenesis and are increased during fasting, infection, and trauma.
  • Glucocorticoids promote proteolysis (protein breakdown) in peripheral tissues, providing amino acids for hepatic glucose production.
  • Insulin suppresses hepatic gluconeogenic enzyme expression and promotes protein synthesis.

Protein Synthesis

  • Amino acid uptake by peripheral tissues is proportional to the demand for protein synthesis.
  • DNA in the nucleus contains the information for protein synthesis.
  • Selected amino acids are used to synthesize other nitrogen-containing compounds, biogenic amines, hormones, and neurotransmitters.
  • In the fed state, insulin increases and stimulates amino acid transporters (system A, ASC, and N) in the liver, muscle, and other tissues.
  • Insulin promotes amino acid uptake and inhibits degradation, favoring protein synthesis.

Process of Protein Synthesis

  • The gene encoding for a specific protein is transcribed into messenger RNA (mRNA) in the nucleus.
  • mRNA leaves the nucleus to be translated into a protein in the cytoplasm.
  • Ribosomes translate mRNA into protein in three phases: initiation, elongation, and termination.
Initiation
  • Assembly of the ribosomal complex (ribosomal RNA, rRNA) occurs, bringing ribosome subunits together at the start codon on the mRNA.
  • This process is catalyzed by initiation factors.
Elongation
  • Codons (three-nucleotide sequences) on the mRNA are read by the ribosomal complex.
  • Transfer RNA (tRNA) gathers amino acids in the cytoplasm and carries them to the ribosome.
  • Amino acids are linked together through peptide bonds to form a polypeptide chain.
Termination
  • A stop codon (three-nucleotide sequence with no complementary tRNA) reaches the ribosomal complex, halting translation.
  • The newly formed protein dissociates and undergoes further modifications to attain its biologically active form.

Nutritional Perspective

  • Protein synthesis is tightly regulated by hormones and other factors.
  • Excessive amino acid intake does not necessarily increase protein synthesis unless someone is not acquiring the daily recommended allowance of protein.
  • Cells dictate the rate of protein synthesis in response to local (autocrine and paracrine) or distant (endocrine) factors.
  • Excess amino acids are diverted to other pathways like oxidation, gluconeogenesis, lipid synthesis, ketogenesis, and the formation of nitrogen-containing compounds.

DNA, RNA, and Protein Synthesis

  • DNA -> RNA -> Protein
  • mRNA (Messenger): Carries genetic information from the nucleus to the cytoplasm, where translation occurs on ribosomes.
  • rRNA (Ribosomal): Subcellular structures (RNA complexed with proteins) on which protein synthesis occurs.
  • tRNA (Transfer): Carries amino acids to ribosomes and ensures their incorporation into the growing polypeptide chain.

Exercise and Protein Synthesis

  • Regular exercise, particularly resistance training, causes an anabolic response in skeletal muscles, leading to increased muscle mass.
  • Resistance training increases protein synthesis and muscle mass.
  • There is no compelling evidence that increasing protein intake beyond the RDA enhances the anabolic effect of exercise.

Hormonal Regulation

  • Hormones that promote protein synthesis: insulin, growth hormone, and testosterone.
  • Insulin promotes amino acid uptake in skeletal muscles and reduces protein breakdown.
  • Growth hormone (GH) acts through insulin-like growth factors IGF-1 and IGF-2 and has more obvious effects during growth and development.
  • Testosterone exerts a potent protein-synthesis effect, particularly in skeletal muscles.
  • Synthetic anabolic steroids can improve sports performance but can lead to health problems and are considered illegal drugs.

Catabolic Hormones

  • Cortisol and thyroid hormone triiodothyronine (T_3) induce protein breakdown.
  • Cushing Syndrome (overproduction of cortisol) leads to weak muscles and less dense bones.
  • Hyperthyroidism (excess thyroid hormones) results in increased basal metabolic rate, weight loss, accelerated protein breakdown, and reduced muscle mass.

Muscle Hypertrophy and Atrophy

  • Anabolic factors promote muscle hypertrophy and mass.
  • Catabolic factors promote muscle atrophy.
  • Examples of anabolic factors include insulin, growth hormone, and testosterone.
  • Examples of catabolic factors include cortisol and T_3.

Protein Turnover and Aging

  • There is a constant rate of protein turnover, with the balance between anabolic and catabolic factors determining net protein accretion or loss.
  • In young adults, anabolic factors prevail.
  • After age 50, catabolic factors predominate, leading to a decline in muscle mass at a rate of approximately 1-2% per year.
  • Exercise and adequate protein intake can attenuate this loss.

Protein Requirements for Athletes

  • Athletes may require more protein than sedentary people to support tissue repair and growth, increased energy supply, and oxygen-carrying capacity.
  • American College of Sports Medicine, American Dietetic Association, and Dietitians of Canada Joint Position Statement recommendations:
    • Non-vegetarian endurance athletes: 1.2 to 1.4 g/kg BW/day
    • Non-vegetarian strength athletes: 1.2 to 1.7 g/kg BW/day
    • Vegetarian endurance athletes: 1.3 to 1.5 g/kg BW/day
    • Vegetarian strength athletes: 1.3 to 1.8 g/kg BW/day
  • Protein intakes greater than ~1.6 g/kg/day do not further contribute to resistance exercise training-induced gains in fat-free mass.
  • Endogenous sources like mucosal cells provide ~50 g of protein/day, and degradation of digestive enzymes and glycoproteins provides another ~17 g of protein/day.

Protein Supplementation

  • Athletes may not need to supplement if their diet meets their energy needs and includes high-quality protein.

Protein Intake per Meal

  • The maximal rate of protein synthesis is reached in young adults after ingesting ~20-25g of high-quality protein.
  • Protein intake beyond this amount in a single meal is believed to be oxidized for energy or transaminated to form urea and other organic acids.
  • A study by Areta et al. (2013) found the greatest muscle protein synthesis response when subjects consumed 4 servings of 20g of whey protein during the recovery period.
  • Typical protein intake for individuals aiming to potentiate muscle hypertrophy is 2-4 times this amount.

Timing of Protein Intake

  • Muscle protein synthesis (MPS) is suppressed during exercise but increases after exercise.
  • Intense resistance exercise can increase MPS for up to 48-72 hours post-exercise.
  • Ingestion of protein immediately after resistance exercise can increase MPS beyond exercise alone.
  • Increased amounts of amino acids, rather than glucose, enhance post-exercise MPS.
  • Insulin's anticatabolic effect contributes to post-exercise muscle gain, provided protein intake is sufficient.
  • Consumption of ~20-25 g of rapidly absorbed protein (e.g., Whey or bovine milk) containing ~8-10 g of essential amino acids can maximally stimulate MPS after resistance exercise in young healthy individuals.

Source of Protein

  • There has been debate regarding whether animal and plant protein are equally effective in providing essential amino acids.
  • A systematic review found no significant differences between animal versus plant protein with respect to lean mass and muscle strength, but there was a favoring effect of animal protein on percent lean mass.
  • Plant-based proteins may have a less anabolic effect due to lower digestibility, lower essential amino acid content (especially leucine), and deficiencies in sulfur amino acids or lysine.
  • Plant amino acids may be directed toward oxidation rather than muscle protein synthesis.