Protein I Flashcards
Where does protein digestion begin and what occurs?
Begins in the stomach where HCl reduces the pH of the stomach
What does acidification in stomach do for protein digestion?
Low pH favors protein denaturation and activates pepsinogen to pepsin
What is pepsin?
Gastric protease
Endopeptidase - cleaves internal peptide bonds
Secreted as inactive zymogen known as pepsinogen
Stable and active at low pH
Describe pepsin activation
Pepsinogen inactive because active site blocked by conformation structure
Low pH alters pepsinogen conformation
Small peptide is removed via hydrolysis and the active site is unblocked
What reaction can pepsin catalyze?
Autocatalytic reaction where pepsinogen generates active pepsin from itself
What is the function of pepsin?
Cuts proteins into large peptide fragments and contributes to formation of partially digested food (chyme)
Cleaves bonds formed by amino groups of aromatic amino acids and leucine
How does protein digestion continue in the intestinal lumen?
Chyme enters the intestines and stimulates the cells of intestinal mucosa to release the hormones, secretin and cholecystokinin into the blood
What is the function of secretin?
Stimulates the pancreas to release bicarbonate (HCO3) rich fluid which neutralizes the acidic chyme
What is the function of cholecystokinin?
Stimulates release of bile from the gallbladder and release of digestive enzymes from pancreas into the lumen of the small intestine
What are the pancreatic digestive enzymes?
Trypsin
Chymotrypsin
Elastase
Carboxypeptidase A and B
All secreted as inactive zymogens and their activation starts with enteropeptidase
What is enteropeptidase?
Membrane anchored protease, found on surface of mucosal villae.
Converts trypsinogen into active trypsin
What occurs when trypsin is activated?
Cascade of enzyme activation is initiated.
Trypsin autoactivates itself and then activates the rest of the zymogens and liberase chymotrypsin, elastase, and carboxypeptidase A and B
Pancreatic proteases and peptidases then generate a mixture of free amino acids and short peptides
Acute Pancreatitis
Causes - Alcohol, gallstones, infections. Premature activation of trypsin within the pancreas
Symptoms - Abdominal pain, nausea, vomiting, and pancreatic necrosis (advanced)
How are amino acids absorbed?
In the intestinal lumen, free amino acids and small peptides are present and must be transported across intestinal epithelial membrane by carrier transporters that require energy input provided by:
Proton gradient
Sodium electrochemical gradient
What does the proton dependent transporter transport on apical side on intestinal lumen?
Di and Tri peptides -> di and tri peptidases produce free amino acids from the peptides
What does the sodium dependent transporter transport on apical side on intestinal lumen?
Free amino acids
What structure of protein can enter the blood?
Free amino acids
Celiac Disease
Causes:
- Incomplete digestion of gluten
- alpha gliadin triggers inflammation
- loss of villi, flat small intestines
Symptoms: Abdominal cramps and bloating when consuming gluten and nutrient deficiency
Treatment: Gluten free diet
Pt presents with pellagra-like light sensitive rash and neutral amino acid aciduria
Hartnup Disease
Causes:
- Deficiency in sodium dependent transporter of neutral amino acids across the intestine and kidney membranes -> impacts intestinal absorption of amino acids and kidney reabsorption of amino acids
Other symptoms: Lack of tryptophan, precursor of niacin
What is the function of L-system transporters?
Transports large, neutral aromatic aa (Phe, Trp, Tyr)
Independent of sodium symport or ATP hydrolysis
aa released in blood by facilitated diffusion
What is the function of sodium amino acid carrier system (A and ASC)?
Transports amino acids along with sodium
Sodium is pumped by Na-K ATPase from the cell into the blood
What is the amino acid pool?
When dietary protein digestion and absorption, free amino acids enter the portal circulation and are distributed to cells, tissues, and organs via the amino acid pool.
What are characteristics of the amino acids pool?
Size of pool in humans is about 100g
Endogenous amino acids originate from body proteins
Bulk of amino acids are used as precursors for protein synthesis
Rest used as energy fuels for catabolism
Ammonium ions are end products that are excreted by kidneys or converted to nontoxic urea by the liver
What are the essential amino acids? (think Pvt Tim Hall)
Amino acids that we cannot synthesize
Phenylalanine
Valine
Threonine
Tryptophan
Isoleucine
Methionine
Histidine
Arginine - infants
Leucine
Lysine
Why is arginine an essential amino acid?
Healthy adults can make arginine, it is essential for young children
Children cannot make sufficient amount of arginine for needs during periods of growth.
Nitrogen Content
Well balanced diet - nitrogen balance
Positive nitrogen balance - protein synthesis exceeds degradation and occurs during periods of growth
Negative nitrogen balance - protein degradation exceeds synthesis and this occurs during wasting disease or starvation
Equal - steady state