Macronutrient Metabolism-Proteins

What are some of the advantages of peptide absorption?

-The majority of amino acids are absorbed as peptides -The ability to administer peptides directly into the blood as in parenteral nutrition is of nutritional significance since some amino acids are insoluble and unstable in their free form. Administration in peptide form allows nutrients to be provided in situations were traditional free amino acid parenteral mixtures are ineffective.

What is the RDA for protein for adults?

0.8 g/kg

Describe the four types of protein structure and organization.

1. Primary: Sequence of amino acids 2. Secondary: 3 types-helix, conformation, Random coil 3. Tertiary: Structure-Linear, Globular, Spherical. Ex. myoglobin. 4. Quarternary: Two or more chains that are all tangled up and folded up, associated together Resulting proteins are usually called oligomers. Ex. hemoglobin

List and define the functional categories of proteins. Give an example of each.

10. Other Roles: Glycoproteins: attached to CHO Proteoglycans: subclass of glycoproteins: chondroitin sulfate

List and define the functional categories of proteins. Give an example of each.

2. Messengers, i.e., Hormones

List and define the functional categories of proteins. Give an example of each.

3. Structural Proteins: Actin Myosin Contractile fibrous

List and define the functional categories of proteins. Give an example of each.

4. Buffers: Can accept or donate hydrogen ions

List and define the functional categories of proteins. Give an example of each.

5. Fluid Balance: Main protein in blood is albumin Attract water and keep it in the blood Low albumin can result in ascites and edema

Incomplete protein

A dietary protein source that is missing or contains insufficient amounts of one or more indispensible amino acids needed for protein synthesis in the body.

Ammonium ion

A positively charged polyatomic ion with the chemical formula NH+4. It is formed by the protonation of ammonia (NH3). Ammonium is also a general name for positively charged or protonated substituted amines and quaternary ammonium cations (NR+4), where one or more hydrogen atoms are replaced by organic groups (indicated by R).

Complete protein

A protein that contains all the essential amino acids in the approximate amounts needed by humans.

Carnitine

A quaternary ammonium compound that is present especially in vertebrate muscle, is involved in the transfer of fatty acids across mitochondrial membranes, and in humans is obtained from food (as meat or milk) or is synthesized from a lysine derivative.

What is the difference between creatine and creatinine?

Creatinine is a break-down product of creatine phosphate in muscle, and is usually produced at a fairly constant rate by the body

The digestable indispensible amino acid score (DIAAS) is a newer method to assess protein quality. How different is this new method from the protein digestibility corrected amino acid score (PDCAAS)?

DIAAS measures amino acid digestibility in the ileum where PDCAAS measures amino acid digestibility in the colon.

How is hydrochloric acid involved in protein digestion?

Denatures the protein

What is (are) the limiting amino acid(s) in grains vs legumes.

Grains: lysine, threonine (sometimes) and tryptophan (sometimes) Legumes: Methionine (sulfur-containing amino acids)

a-keto acid

One of two ketone derivatives of glutaric acid. Its anion, α-ketoglutarate is an important biological compound. It is the keto acid produced by deamination of glutamate, and is an intermediate in the Krebs cycle.

Describe the mechanisms for amino acid and peptide absorption.

Site of Absorption Most products of digestion are absorbed in proximal small intestine, mostly duodenum and jejunum Absorption Mechanisms Almost all cells have a.a. transporters

Describe the process of amino acid catabolism.

Starts with transamination and deamination Transamination: Nitrogen is being transferred to another compound Amino group is being removed from one a.a. and putting it on a skeleton to make a new a.a. Can be reversed AST and ALT come from the liver Deamination: Complete removal of the amino group without transferring it to another carbon skeleton Often associated with breaking an a.a. for energy

Creatine

is a nitrogenous organic acid that occurs naturally in vertebrates. Its main role is to facilitate recycling of adenosine triphosphate (ATP), the energy currency of the cell, primarily in muscle and brain tissue. This is achieved by recycling adenosine diphosphate (ADP) to ATP via donation of phosphate groups. Creatine also acts as a pH buffer in tissues.

What is mTOR and what role does it play in relation to protein synthesis?

mTOR is mechanistic target of rapamycin. mTOR links with other proteins and serves as a core component of two distinct protein complexes, mTOR complex 1 and mTOR complex 2, which regulate different cellular processes. As a core component of both complexes, mTOR functions as a serine/threonine protein kinase that regulates protein synthesis.

How is the protein information on food labels regulated?

-Amount protein in grams -%DV if food intended for children ≤ 4 yrs -PDCAAS used to calculate %DV for ≥ 1 yr -PER used to calculate % DV for infant formula/baby food -Casein used a reference protein

What determines whether an amino acid is essential (indispensable) or non-essential (dispensable)?

-Essential (Indispensable) Human body cannot synthesize from other a.a. or hydrogen or carbon. Must be in the diet. -Nonessential (Dispensable) -Conditionally Essential Depends on conditions. Stress mode may need a lot of a particular a.a., then that a.a. becomes essential.

What are the sources of protein for the body?

-Exogenous: Comes from food Meat, eggs, dairy, beans, legumes, almost all plant products have some protein except for fruit (.5g/serving) -Endogenous: Breakdown of muscles Digestive enzymes Intestinal cells from cellular turnover

How do amino acids enter other cells of the body (e.g. liver, renal, red blood cells...)?

-Liver cells (hepatocytes): Liver monitors a.a. concentration and metabolizes a lot of them to signal body to create amino acids if the body needs more. -Renal Cells, Erythrocytes, Neurons: y-glutamyl cycle: different than other transport systems because it uses different compounds

Describe several ways that amino acids can be classified.

-Net electrical charge in an aqueous solution; can have a positive, negative, or neutral charge -Polarity: Based on functional groups and whether they can form H bonds with other compounds -Essentiality: Essential (Indispensable) Nonessential (Dispensable) Conditionally Essential

Describe the digestion of protein including the enzymes in each section of the GI tract, it's zymogen and activator.

-Stomach: Pepsin: secreted in an inactive form (zymogen) pepsinogen; HCl activates pepsin, which works on the protein -Small Intestine→Pancreatic Juice Zymogens Trypsinogen trypsin by enteropeptidase, then activated trypsin converts rest of trypsionogen. Trypsin activates the others: Chymotrypsinogen Procarboxypeptidase A & B Proelastase Collagenase -Endopeptidases: work on the bonds on the inside of the chain Trypsin: Chymotrypsin Elastase (from proelastase) Collagenase -Exopeptidases: Exopeptidases work on the bonds near the ends (outside) Carboxypeptidase A: acidic a.a. Carboxypeptidase B: basic a.a. -Other peptidases Produced along brush border of small intestine Aminopeptidases: work on near the amino end of the chain (NH end) Dipeptidylamionpeptidases: work on the end Tripeptidases: work on tripeptides

List and define the functional categories of proteins. Give an example of each.

1. Catalyst (Enzymes) Active site The substrate gets converted to the product Cofactors and Coenzymes Assist Some enzymes have to have cofactors or coenzymes to function Coenzymes are normally B vitamins Cofactors are usually minerals Functions Speed up digestion reactions Involved in energy production Blood coagulation

List and define the functional categories of proteins. Give an example of each.

6. Immunoproteins: Immunoglobulins and antibodies

List and define the functional categories of proteins. Give an example of each.

7. Transporters: Albumin Transferrin Lipoproteins Retinol-binding protein-transport vitamin A

List and define the functional categories of proteins. Give an example of each.

8. Acute Phase Responders: Respond to acute, critical illnesses to stimulate the immune system and promote healing CRP, fibronectin, orosomucoid, haptoglobin, serum amyloid A, ceruloplasmin, metallothionein

List and define the functional categories of proteins. Give an example of each.

9. Heat Shock Proteins: Synthesized in the presence of heat or oxidative stress. May protect cell by directing protein folding and unfolding to maintain and repair the cell

Describe the general structure (parts) of an amino acid.

A central carbon (C), at least one amino group (-NH2), at least one carboxy group (-COOH), and a side chain (R group) that makes each amino acid unique.

What constitutes a complete versus an incomplete protein?

A complete protein has all indispensible amino acids in the approximate amounts needed by humans. An incomplete protein have too little of one or more indispensible amino acids.

Peptide Bond

A covalent chemical bond linking two consecutive amino acid monomers along a peptide or protein chain.

Urea cycle

A cycle of biochemical reactions that produces urea ((NH2)2CO) from ammonia (NH3). The urea cycle converts highly toxic ammonia to urea for excretion

How does the body "mediate" (control) protein turnover?

Amino acid concentrations within cells serve as sensors and modulate intracellular signaling pathways. mTOR integrates signals from insulin and leucine to enhance protein synthesis. Inhibition of mTORC1 along with the presence of other compounds/events stimulates degradation. Cellular protein degradation increases when cellular quantities of amino acids are limited or imbalanced. This alters the binding of transcription factors to promoter regions on selected genes and inhibit the production of proteins involved in protein synthesis.

Describe various uses of the different classifications of amino acids: aromatic, sulfur-containing, branched chain, others.

Aromatic amino acids: Phenylalanine and tyrosine: partially glucogenic because they are degraded to fumarate. Also catalyzed to acetoacetate and thus are partially ketogenic. Sulfur-containing: Methionine: glucogenic

Give examples of amino acids that can be converted to another amino acid as well as some of the other important body compounds that are synthesized from each classification and any particular genetic disorders of amino acid metabolism.

Aromatic: Phe>>>Tyr Tyr>>>L-dopa & catecholamines OR Tyr + iodine >>> thyroid hormones OR Tyr >>>Melanin OR Tyr>>>>Fumarate (Krebs) or Acetoacetate (Ketones) Tryptophan Partially glucogenic and ketogenic Try>>>serotonin >>>melatonin (hormone) Try>>> Niacin (B3)>>>NAD+ Genetic Defects α-ketoadipic aciduria Glutaric aciduria type I Both result in seizures, acidosis, and motor & developmental delays Sulfur-Containing: Met>>>cysteine & taurine Met>>>S-adenosyl methionine (SAM) Carnitine: fatty acid oxidation Creatine Epinephrine Purines Nicotinamide Methylation of DNA Disorders of methionine metabolism Hypermethionemia Homocystinuria

What is the usual "reference protein" used for evaluating protein quality?

Casein

What are some clinical characteristics of marasmus?

Chronic insufficient protein and energy intake Depleted skeletal/somatic protein and adipose Visceral proteins usually WNL or slightly below Will also have vitamin and mineral deficiencies Lab values may be normal as the body adjusts

Explain the concept of complementary proteins or "mutual supplementation."

Combining proteins with amino acid patterns that complement one another. Amino acids tend to be better absorbed when the complementary proteins are consumed together

Glutathione

Composted of three amino acids - cysteine, glycine, and glutamate - glutathione can be found in virtually every cell of the human body. ... A primary function of glutathione is to alleviate this oxidative stress.

Conditionally essential amino acid

Conditional amino acids are usually not essential, except in times of illness and stress. Conditional amino acids include: arginine, cysteine, glutamine, tyrosine, glycine, ornithine, proline, and serine.

Explain the roles of various hormones involved in promoting and inhibiting protein synthesis.

During prolonged periods in which food is not eaten, protein synthesis still occurs, but at a much lower rate, and protein degradation predominates. The degrative processes are stimulated by epinephrine and cortisol release and by the higher glucagon-to-insulin ratio in the blood. This diminishes insulin's ability to inhibit protein degradation and overall rate of protein synthesis. During post-absorptive periods, the glucagon-to-insulin ratio favoring glucagon stimulates the hepatic synthesis of some proteins, as enzymes for gluconeogenesis and ureagenesis. Higher blood cortisol concentrations further promote muscle protein catabolism and hepatic use of the amino acids for gluconeogenesis and ureagenesis. Insulin is secreted in response to a rise in incretins (glucose-dependent insulinotropic peptide and glucagon-like peptide 1 released in response to glucose in the digestive tract), a rise in blood glucose, and a rise in some blood amino acid concentrations generally increase protein synthesis and decreases protein degradation. This occurs to a greater extent if both CHO and protein-containing foods are coingested versus ingestion of either CHO or protein alone. Insulin, upon binding to its receptors in cell membranes, exhibits multiple actions to promote protein synthesis. Insulin -synthesis Glucagon - catabolism Epinephrine - catabolism Glucocorticoids - catabolism Growth hormone - net synthesis

What are some of the products of the metabolism of these carbon skeletons?

Energy production: the complete oxidation of amino acids generates energy, along with water, CO2/HCO3-, and ammonia/ammonium ions. Amino acids are used for energy production when the diet is inadequate in energy. Glucose Production (gluconeogenesis): occurs primarily in the liver, but also in the kidneys and small intestine. The carbon skeletons of several amino acids can be used to synthesize glucose. )(oxaloacetate comes from the carbon skeleton of aspartate and pyruvate comes from the skeleton of alanine, asparagine may also be converted to oxaloacetate, and glycine, serine, cysteine, tryptophan, and threonine can be converted to pyruvate for glucose production. Valine and methionine are also glucogenic) Ketone body production: catabolism of the amino acid must generate acetyl-CoA or acetoacetate, which are used for the formation of ketone bodies. (phenylalainine, isoleucine is partially glucogenic, yielding succinyl-CoA, but also ketogenic, yielding acetyl-CoA; threonine and tryptophan are also partially glucogenic yielding succinyl-CoA or pyruvate depending on its pathway of degradation, and partially ketogenic to acetyl-CoA. Leucine and lysine are the only totally ketogenic amino acids) Cholesterol production: the oxidation of several amino acids yield acetyl-CoA which can be metabolized to produce cholesterol (isoleucine, leucine, lysine, tryptophan, and threonine) Fatty acid production: in times of excess energy and protein intakes coupled with adequate CHO intake, the carbon skeleton of amino acids may be used to synthesize fatty acids. (leucine can be used to synthesize fatty acids in adipose tissue.)

What is meant by glucogenic or ketogenic amino acid?

Glucogenic amino acids yield pyruvate or intermediates of the TCA cycle when oxidized, ketogenic amino acid catabolism yields acetyl-CoA or acetoacetate

What is the primary amino acid used by the enterocytes?

Glutamine

Describe the interorgan flow of amino acids with focus on glutamine, alanine and the branch-chain amino acids.

Glutamine is metabolized in the intestinal cells and used as an intermediate Prevent atrophy, promote growth and proliferation of intestinal cells Glutamate: comes from glutamine metabolism (glutamine with one amino group removed) or from the diet. Can be used to a.a. Alanine, which can travel to liver and be converted to glucose Synthesizes ornithine for the urea cycle or can go to the kidney to create another a.a. in the kidney Stress requires a lot of glutamine to function properly, some enteral formulas have been fortified with glutamine to prevent intestinal atrophy Alanine can transfer amino groups (transanimation) from its amino group to a different carbon skeleton and become a carbon skeleton itself Gluconeogenesis in the glucose-alanine cycle/alanine-glucose cycle Branched-chain: Catabolized to Kreb's cycle intermediates Provide energy Can contribute to glucose or ketones Can contribute to cholesterol synthesis Leucine can supply more ATP than glucose

What are some nutritionally significant nitrogen containing nonprotein compounds and their functions?

Glutathione: major antioxidant with the ability to scavenge free radicals, thereby protecting critical cell components against oxidation. Carnitine: needed for the transport of fatty acids, especially long-chain fatty acids, across the inner mitochondrial membrane for oxidation. Also needed for ketone catabolism for energy. Also forms acylcarnitines from short-chain acyl-CoAs, which may serve to buffer the free CoA pool. Creatine: Key component of energy compound creatine phosphate. Functions as a storehouse for high energy phosphate, which replenishes ATP in a muscle that is rapidly contracting. Carnosine: acts as both a buffer and an antioxidant within muscle cells; it may also reduce calcium needs for muscle contractility. Choline: most is used to synthesize phopatidylcholine and sphingomyelin, major components of cell membranes. Also used in the formation of platelet aggregating factor and for the neurotransmitter acetylcholine. Purine and pyrimidine bases: needed along with a five-carbon sugar and phosphoric acid for the synthesis of DNA and RNA

How was the AI for protein for infants determined?

Infants up to 6 months Different AIs for age and gender. AI was derived from data from infants fed human milk as the primary nutrient source for the first 6 months

What are the two major molecules that enhance mTOR activity?

Insulin and leucine

What determines (or contributes to) each of the structures?

Its functional role

What is the result of sufficient energy intake and insufficient protein intake?

Kwashiorkor

What is the name of the disease, also known as wasting, that would confirm a malnutrition diagnosis?

Marasmus

What are some of the clinical and laboratory signs of these deficiencies?

Marasmus: Will have vitamin and mineral deficiencies Lab values may be normal because their bodies have adjusted Visceral proteins are reflected in albumin and total protein Kwashiorkor: Visceral proteins will be low, albumin will be very low probably because of some infection

Describe the deficiency syndromes associated with protein deficiency.

Marasmus: Chronic insufficient protein and energy intake Depleted skeletal/somatic protein and adipose Viseral proteins usually WNL or slightly below Kwashiorkor: Insufficient protein intake in presence of adequate energy intake Diminished viseral protein status Edema Ascites

How do amino acids enter the circulation?

Most products of digestion are absorbed in proximal small intestine, mostly duodenum and jejunum

Describe the changes that occur in protein content (body mass) with aging.

Muscle accounts for majority of body protein & peaks by gender 44.8% ♂ (20 yrs) 36% ♀ (18 yrs) Lean body mass decreases w/age & gender (sarcopenia) ♀ faster than ♂ Loss of bone mass and atrophy of organs

What are some of the limitations of each procedure?

PDCAAS: Includes not only nitrogen from the test protein but also from endogenous proteins such as from digestive secretions and cells. BV: the equation fails to account for losses of nitrogen through insensible routes such as the hair and nails. NPU: more accurate on animals than on humans

What type of covalent bond constitutes the polypeptide backbone of a primary protein structure?

Peptide bond

List the essential amino acids.

Phenylalanine Valine Threonine Methionine Tryptophan Histidine Isoleucine Leucine Lysine

How is dietary protein quality categorized?

Quality is determined by two factors: indispensable/essential a.a. composition; digestibility If it meets one or the other, it's not as high quality as both together Animal foods meet both most often: eggs are typically the reference food to determine protein quality Soy is also considered a high quality protein Gelatin is not a complete protein and is not a high quality protein.

Describe some of the controversy surrounding excessive protein intakes.

Potential: -Dehydration: prevent with adequate fluid -Kidney damage: not proven in healthy people -Bone damage: conflicting findings -Catabolic effects from acid generation -Anabolic effects (in older adults) from synthesis of bone proteins, or stimulation of insulin-like growth hormone I; or concurrent consumption of increased Ca & PO4

Describe the various procedures used to evaluate protein quality.

Protein Digestibility Corrected Amino Acid Score (PDCAAS): Accounts for limiting AA + digestibility of a protein Divide mg limiting AA in test food by mg limiting AA in ref food and multiply by digestibility of test food (%) Foods w/PDCAAS =100%: casein, egg white, ground beef, tuna This method measures digestibility in the colon. Digestible Indispensible Amino Acid Score (DIAAS): newer method to assess protein quality. Considers the amount, profile, and digestibility of the indispensible amino acids in protein-containing foods. Compares the amount of digesting indispensible amino acid in 1g of a dietary test protein to the amount of the same indispensible amino acid in 1g of reference protein. This method measures the digestibility of amino acids in the ileum. Protein Efficiency Ratio (PER): Body wt gained on test protein/g protein consumed (growing animals) Method used for infant formulas and baby foods Reported on label Oldest of the testing methods Chemical or amino acid score: Determination of indispensable amino acid composition of a food Compared to reference amino acids in egg protein Biological value (BV): a measure of how much nitrogen is retained in the body for maintenance and growth rather than absorbed. Foods with high BV are those that provide the amino acids in amounts consistent with body amino acid needs. Net Protein Utilization (NPU): similar to nitrogen-balance studies. Measures retention of food nitrogen consumed rather than retention of food nitrogen absorbed. Net Dietary Protein Calories Percentage (NDpCal%): can be helpful in evaluation of human diets in which the protein-to-calorie ratio varies greatly.

What is protein turnover?

Protein synthesis and protein degradation

When is protein synthesis highest?

Right after a meal

What makes each amino acid unique?

The R group

Limiting amino acid

The amino acid within a protein with the lowest amino acid or chemical score

Describe the metabolism of the carbon skeleton from amino acid catabolism.

The carbon skeleton is the remaining part once an amino group is removed from an amino acid. Carbon skeletons can be further metabolized with the potential for multiple uses in the cell, depending on the original amino acid from which they were derived and the body's physiological and nutritional state.

Carbon skeleton

The carbon skeleton is the α-keto acids remaining after removal of ammonia from amino acids.

Describe the disposal of the amino group from amino acid catabolism.

The liver is the main site of disposal and has two systems for disposing of Ammonia: Ureagenesis = primary; requires ATP Glutamine synthesis = backup system

Catabolism

The process by which organic molecules are broken down

Deamination

The removal of an amino group from an amino acid

Anabolism

The synthesis of complex molecules in living organisms from simpler ones together with the storage of energy; constructive metabolism.

Describe the concept of "limiting amino acid."

The term limiting amino acid is used to describe the indispensible amino acid that is present in the lowest quantity in food.

Transamination

The transfer of an amino group from one molecule to another, especially from an amino acid to a keto acid.

What are some of the nitrogen-containing waste products used in evaluating protein quality with some procedures?

feces