Protein

Describe a situation where a person would be in positive nitrogen balance. Describe a situation when someone would be in negative nitrogen balance.

-N balance: when the body is excreting more N than its retaining (the body is breaking down more protein than it is making) such during inadequate protein/energy intake, starvation, fasting, trauma, burns illness/infection +N balance: when the body is retaining more N than it is excreting (synthesizing more protein than excreting) such as in actively growing children/infants and during pregnancy

Describe the physiological importance of protein breakdown

1. Rapid removal of critical regulatory hormones (recycle proteins when they are no longer useful/ have provided their purpose --ex: transcription factors) 2. adaptation to new physiologial conditions (deactivate/activate enzymes as needed to adapt---ex: when we fast, glucose decreases= we want the body to stop storing glucose as glycogen and instead we want it to make glucose/gluconeogenesis) 3. quality control (eliminate damaged proteins) 4. immune function (be able to recognize antigens within the body & breakdown those proteins)

List at least 5 examples of protein function

1. Structure 2. Enzymes 3. Hormones 4. Antibodies 5. Fluid Balance 6. Acid-base balance 7. Channels and pumps 8. Transport

Describe the systems responsible for protein degradation

1. Ubiquitin Proteosomal Pathway: a process a protein undergoes before it gets broken down where many ubiquitin molecules attach to the AA that needs to be broken down---- old, worn out proteins get tagged with ubiquitin protein which sends a signal for them to be sent through the proteosomes to allow enzymes to digest the AA and use its parts to build other proteins ---this system allows the body to know to only degrade the damaged proteins and not all proteins 2. Lysosomal System Lysosomes act like a cellular garbage digestive system to degrade proteins--- 1. endocytosis of protein 2. endocytosed protein fuses with lysosome 3. lysosomal enzymes digest the protein 4. AA are released into cytosol to be reused

· Explain various fates of absorbed AA

1. get incorporated into protein 2. are used to synthesize other non-protein containing compounds (neurotransmitters, creatine etc) 3. the amino group can be transaminated into another amino acid (carbon skeleton used for energy, fat, ketones, glucose---transamination is a way to deal with the N if its not being used to make protein)

Discuss BCAA and protein synthesis in the body

BCAA stimulate protein synthesis and has been shown to accelerate protein synthesis in rat studies: Leucine specifically is the primary driver of protein synthesis= high concentrations of leucine will stimulate protein synthesis by activating mTOR (pathway to increase protein synthesis) and inhibit protein degradation in skeletal muscle

What are BCAAs? How are they metabolized?

BCAA=branched chain amino acids (leucine, isoleucine, and valine) function to provide anabolic signaling to promote protein synthesis BCAAs are the first AA to be broken down for gluconeogenesis Metabolism: 1. Branched chain amino acid transferase removes amino group from BCAA and the alpha ketogluterate will accept the amino acid to become glutamate 2. branched chain ketoacids get acted on by branched chain alpha keto acid dehydrogenase 3. valine produces succinyl CoA (glucogenic) leucine produces acetyl CoA (ketogenic) isoleucine can be used in multiple pathways (ketogenic * glucogenic) ........?

Explain why the urea cycle activity would be elevated during a short term fast

Because there will be an increase in deamination of AA to use as energy for gluconeogenesis The body is doing gluconeogenesis to monitor glucose during times of not eating. When there is no glucose, protein and AA will be used to make glucose (deamination)----the breakdown of protein for gluconeogenesis will increase nitrogen which needs to be excreted. The nitrogen will get excreted via the urea cycle, so the urea cycle activity will increase

Explain how dietary proteins are digested.

Digestion starts in the stomach but the majority of digestion occurs in the small intestine: 1. gastric cells release gastrin causing the release of gastric juices 2. HCl in gastric juices denatures the protein and converts pepsinogen to pepsin which begins to digest the proteins by hydrolyzing peptide bonds (denaturing the protein exposes the peptide bonds making it easier for enzymes to reach them) 3. Partially digested proteins enter the small intestine and cause the release of the hormone secretin and CCK 4. Secretin and CCK stimulate the pancreas to release enzymes (proteases) and bicarb into the intestine. (bicarb neutralizes the chyme) 5. Pancreatic enzymes (proteases) are converted to active enzymes. The active enzymes digest polypeptides into tripeptides, dipeptides and free AA 6. intestinal enzymes in the lumen of the small intestine and within mucosal cells complete protein digestion

T/F creatine cannot be synthesized in the body and has to be obtained through the diet

False

T/F The lysosomal pathway is the only route that cells possess to degrade proteins

False---ubiquination system

How do proteins function as hormones?

Function as chemical messengers and signals. Proteins regulate metabolic body processes such as promoting enzyme activity. *Some, but not all, hormones are made of protein Examples of hormones that are proteins are insulin,glucagon, and sex hormones Remember, injected insulin will bypass the gut= bypass protein breakdown, if it went to the gut it would breakdown (bc its a protein) and lose its function

So what happens when you have liver disease? What builds up? What about when you have kidney disease?

In liver disease, ammonia cannot be converted to urea for excretion so it accumulates Additional sources of ammonia come from the degradation of bacteria and blood from GI bleeds in the case of varices When you have kidney disease the ammonia is able to be converted to urea but the kidneys cannot effectively excrete urea so it accumulates (high BUN)

How are amino acids altered in liver disease?

In patients with HE, the ratio of BCAA: AAA is altered to where BCAA is decreased and AAA is increased

Should patients with metabolic encephalopathy be given BCAA formulas? Why or why not?

In patients with HE, the ratio of BCAA: AAA is altered to where BCAA is decreased and AAA is increased However, HE is no longer treated with BCAA supplementation because most patients can tolerate a mixed protein diet and the evidence supporting BCAA enriched formulas is not associated with significant improvements or survival benefits in pts with HE

Briefly describe the ubiquitin-proteasomal system. What is it used for?

It is a system consisting of a series of enzymatic rxns to breakdown proteins functions: 1. rapid removal of proteins (degradation of specific proteins) 2. regulation of gene transcription 3. quality control mechanism (eliminates damaged proteins) 4. the immune system ( 5. source of AA (provide building blocks for gluconeogenesis, new protein synthesis, energy production in times of inadequate kcal intake/catabolic stress)

Kwashiorkor vs Marasmus

Kwashiorkor: is a type of malnutrition characterized by severe protein deficiency. It causes fluid retention and a swollen, distended abdomen. Kwashiorkor most commonly affects children, particularly in developing countries with high levels of poverty and food insecurity (lack of protein/essential nutrients. Marasmus: is a severe form of protein-energy undernutrition. It results from an overall lack of calories. Marasmus is a deficiency of all macronutrients: carbohydrates, fats, and protein **The main difference between them is that kwashiorkor is predominantly a protein deficiency, while marasmus is a deficiency of all macronutrients — protein, carbohydrates and fats

Essential vs nonessential AA vs conditionally essential. In what scenario(s) would a nonessential AA be considered a conditionally essential AA?

Non-essential AA= the body can make sufficient quantities needed on its own (the body has precursors to create the AA) Essential AA= must be supplied by the diet because the body cannot make them on its own Conditionally Essential AA= AA that are normally non essential but become essential under certain circumstances such as: 1. improper organ function ex: in premature infants, liver disease (impairs methionine and phenylalanine metabolism) 2. inborn errors of AA metabolism ex: PKU, a genetic condition where phenylalanine cannot be properly metabolized leading to tyrosine(the precursor to phenylalanine) to become an essential amino acid

PKU, dietary implications

PKU is a genetic condition where phenylalanine cannot be properly metabolized leading to tyrosine(the precursor to phenylalanine) to become an essential amino acid. If untreated, PKU causes neurologic problems such as seizures and hyperactivity, among other problems. Phenylalanine hydroxylase, the enzyme that converts phenylalanine to tyrosine, exhibits little to no activity in people with the inborn error of metabolism known as classic phenylketonuria (PKU). Without adequate hydroxylase activity, tyrosine is not synthesized in the body and must be provided completely by the diet The disorder is treated with a phenylalanine-restricted diet, which means that the ingestion of natural protein containing foods must be extremely limited, and tyrosine must be added to the diet because it cannot be made in the body. In addition, labels on products that contain aspartame (brand name Equal®) must have a warning indicating that the product contains phenylalanine and thus its use must be restricted by those with PKU

What enzymes are involved in protein digestion?

Pepsin (stomach) Trypsin (sm intestine) Chymotrypsin (sm intestine) carboxypeptidase (sm intestine) amino peptidase (sm intestine)

Describe the role of the urea cycle and the cycle's common intermediates with the TCA cycle.

The urea cycle converts ammonia to urea for excretion

Describe urea cycle

The urea cycle is a process that converts toxic ammonia to urea so it can be excreted Once urea is formed, a majority of it travels in the blood to the kidneys for excretion in the urine and a smaller portion of urea will be secreted from the blood to the intestinal lumen where bacteria will degrade it and create more ammonia *the last step of deamination of glutamate is the first step of the urea cycle

How do BCAAs impact protein synthesis?

They promote protein synthesis

How do proteins function in transport?

They provide a means for carrying substances such as vitamins, minerals and other nutrients An example of proteins that acts as transporters 1. lipoprotein which transports cholesterol and TG in the blood 2. Albumin

Explain the process of transamination. What is the purpose of transamination?

Transamination is a chemical rxn where the nitrogen from 1 AA is transferred to another compound: 1. the AA reacts with alpha ketoacid (carbon skeleton) 2. the AA loses its nitrogen and the alpha ketoacid gains the nitrogen 3. a new AA is formed The purpose of transamination is to convert essential AA to non-essential AA The amino group is typically transferred to alpha keto gluterate to make glutamate

Transamination vs Deamination

Transamination: a process where the nitrogen from an AA is transferred to another compound Deamination: involves the removal of the amino acid group without any transfer to another compound (remember, if we remove the amino group, you then need to dispose of the nitrogen in the urea cycle) After an AA is deamination, the end products are carbon skeletons

T/F infection and/or trauma increases glutamine use by the cells in the body

True

Define 'conditionally essential' amino acids and give an example

Tyrosine in PKU becomes conditionally essential meaning that the body does not have the enzyme needed to convert phenylalanine to tyrosine = tyrosine cannot be produced by the body and must therefore be obtained from the diet

What is meant by the terms 'glucogenic' and ketogenic' amino acids What determines whether amino acids are considered glucogenic or ketogenic?

When amino acids get deaminated (amino group is removed), the end products are carbon skeletons (alpha keto acid) which can be used in a variety of ways. The terms glucogenic and ketogenic are ways to use the carbon skeleton Glucogenic AA carbon skeletons are degraded to pyruvate or an intermediate of the krebs cycle and get used to produce new glucose (used in gluconeogenesis and subsequent glycogen formation) Ketogenic AA are degraded to acetyl CoA or acetoacetate and can be used to form ketone bodies, FA synthesis or used to make ATP via TCA cycle--they CANNOT be used in gluconeogenesis (ex leucine and lysine)

How do proteins function in acid-base balance?

acting as buffers (donate H+ when pH is high and accept H+ when PH is too low) Although proteins play a role in acid-base balance, remember that proteins are not the main controllers of acid base balance (kidneys/lungs play more of a role)

Where does the Urea cycle happen?

begins in the mitochondria of the liver and ends in the cytoplasm of the hepatocyte

How do proteins function as enzymes?

catalyze metabolic reactions- synthesize and breakdown compounds ** ALL enzymes are proteins

T/F the general structure of an amino acid contains a central carbon atom, an amino group, a methyl group and a variable side chain

flase, it contains a carboxylic acid group not a methyl group

What products of protein digestion are absorbed into the enterocyte?

free AA dipeptides tripeptides

How do proteins function as antibodies?

immunoproteins (immunoglobulins (Ig) or antibodies (Ab))

Why might BCAAs be added to an enteral/parenteral formula? What population would this formula be targeted to?

in theory, to protect the mm from breakdown in Hypermetabolic patients or patients with Chronic liver disease, liver failure however evidence is not conclusive

How do proteins function in fluid balance?

proteins help attract and keep water inside a particular area and contribute to osmotic pressure. Diminished blood/plasma concentrations of proteins result in a decrease in plasma osmotic pressure. When protein concentrations in the blood are less dense than normal, fluid "leaks" out of the blood and into interstitial spaces and causes edema Albumin is a major protein in regulating fluid balance.

How do proteins function in structure?

provides structure to skeletal mm, bones (collagen), cell membranes, and lipoproteins examples of structural proteins are: 1. acitn and myosin in skeletal muscle 2. collagen, elastin, and keratin

T/F BCAAs are primarily utilized by skeletal muscle and cardiac muscle

true

T/F pepsinogen is converted to pepsin in the stomach and is responsible for protein digestion

true