Quiz 6

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What is the purpose of digestion?
To prepare large biomolecules (proteins, lipids, polysaccharides) for absorption and transport
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What is used to degrade large molecules for digestion?
Hydrolytic enzymes (hydrolases)
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What is the mechanism of action for hydrolytic enzymes?
They cleave their substrates by the addition of a molecule of water
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Proenzymes / Zymogens
Inactive precursors of digestive enzymes that are secreted from the pancreas
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What are the 3 steps of turning proenzymes/zymogens into active enzymes?

1. Exist in granules near the cell membrane, in response to certain signals the granules fuse with the cell membrane
2. Contents of the granules are expelled into the lumen of the intestine
3. Activated when a part of the inactive precursor is proteolytically cleaved
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Enteropeptidase / Enterokinase
Enzyme anchored to the epithelial cells of the small intestine, converts inactive trypsinogen into active trypsin

* trypsin then activates other pancreatic proenzymes
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What 3 zymogens does trypsin activate?

1. Chymotrypsin
2. Procarboxypeptidase
3. Proelastase
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How does the zymogen pepsinogen get activated?
Pepsinogen has a small amount of enzyme activity and can activate itself to some degree in an acidic environment, active pepsin activates the remaining pepsinogen
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Proteolytic Enzymes (Proteases)
Enzymes secreted by the stomach and pancreas to digest proteins into amino acids
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Alpha-Amylase
An enzyme in the pancreas and saliva that cleaves polysaccharides into monosaccharides
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Where does digestion first begin?
In the mouth where food is mechanically degraded into a slurry that is more readily attacked by hydrolytic enzymes
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Saliva is secreted by what?
Salivary glands
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Saliva is an aqueous solution that contains what 6 components? What are their 2 main purposes?
Facilitate homogenization of food and lubricate the slurry so it can be swallowed:


1. Na+
2. K+
3. Cl-
4. HCO3-
5. Mucoproteins

To cleave alpha-1,4 glycosidic bonds


6. alpha-amylase
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What produces the highly acidic environment in the stomach? What is the purpose of the environment?
Acid environment of the stomach is generated by H+-K+ ATPase to denature proteins and make them more susceptible to digestion by proteolytic enzymes (like pepsin)
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Excessive acid generation causes what disease? How is it treated?
Can result in gastroesophageal reflux disease (GERD) that can be treated with H+-K+ ATPase inhibitors like omeprazole
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Secretin
A hormone that causes the release of sodium bicarbonate which neutralizes stomach acid
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Cholecystokinin (CCK)
Hormone that stimulates the release of digestive enzymes from the pancreas and secretion of bile salts from the gallbladder
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Movement of food from the stomach to the small intestine stimulates the secretion of what 2 hormones from small intestinal cells?

1. Secretin
2. Cholecystokinin (CCK)
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Oligopeptides
Small fragments of digested proteins
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Peptidases
Enzymes on the surface of intestinal cells that cleave oligopeptides into amino acids and di- and tripeptides that are then conveyed into the intestinal cell by transporters
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Where are many peptidases found?
Bound to the membrane, can also be found inside the cell
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Antiporters
Transporter that releases amino acids from intestinal cells into the blood
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At least how many transporters exist that bring amino acids and di- and tripeptides into intestinal cells?
7
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Celiac Disease / Gluten Enteropathy
Genetically disposed people have an inflammatory response to gluten-derived peptides (wheat, rye, and barley) because they mimic immunostimulators
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How is Celiac Disease characterized?
The inflammation damages the intestinal lining and impairs nutrient absorption which causes weight loss, diarrhea, and anemia
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What is the frequency of Celiac Disease in caucasians?
1 in 250
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Glutens
Storage proteins in plants that provide amino acids and carbon, nitrogen, and sulfur for growth and development
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What are the 2 gluten proteins in wheat?

1. Gliadin
2. Glutenin
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What is the 1 gluten protein in barley and rye?

1. Secalin
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Gluten proteins are rich in what 2 amino acids?

1. Glutamine
2. Proline
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Glutens are resistant to complete digestion by what 2 types of proteases?

1. Pepsin
2. Pancreatic
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Prolamins
Proteins that have high proline amino acid content, gluten is sometimes called prolamins
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Hartnup Disease
A rare defect in the transporter for tryptophan and other nonpolar amino acids; characterized by rashes, ataxia, delayed mental development, and diarrhea
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What is our primary source of carbohydrates?
Starch
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What are the products after alpha-amylase cleaves starch?

1. Disaccharide maltose
2. Trisaccharide maltotriose
3. Limit dextrin
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After alpha-amylase, what 2 enzymes complete the digestion?

1. alpha-glucosidase
2. alpha-dextrinase
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What 3 things do alpha-glucosidase digest?

1. Maltose
2. Maltotriose
3. Any other oligosaccharides that wasn’t digested by amylase
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What does alpha-dextrinase do?
Digests limit dextrin into simple sugars
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Where are alpha-glucosidase and alpha-dextrinase found?
On the surfaces of intestinal cells
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Lactase
Enzyme that digests lactose (galactose+glucose)
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Sucrase
Enzyme that digests sucrose (glucose + fructose)
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What are the 2 transporters that transports monosaccharides into the intestinal epithelial cells? What is the transporter that releases monosaccharides into the bloodstream?
Transport In:


1. Sodium-glucose linked transport (SGLT) - secondary active transport process
2. GLUT5 - diffusion

Transport out:


1. GLUT2 - diffusion
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What monosaccharide(s) do sodium-glucose linked transporters (SGLT) transport into the intestine? How about GLUT5?
SGLT: glucose and galactose

GLUT5: fructose
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What do triacylglycerols form in the stomach?
Lipid droplets
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What is the role of bile salts in lipid digestion?
Bile salts insert into the lipid droplets to make them more accessible to digestion by lipases
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Lipases
Enzymes secreted by the pancreas that convert triacyclglycerols into 2 fatty acids and monoacylglycerol
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How are the digestion products of lipids carried to intestinal epithelium cells for absorption?
Carried as micelles
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Chylomicrons
Lipoprotein transport particles
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Describe the structure of chylomicrons
Approximately 200nm in diameter and composed of 98% triacylglycerols with proteins and phospholipid on the surface
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How are fatty acids and monoacylglycerol transported into intestinal cells?
By membrane proteins like fatty-acid-binding protein (FABP)
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What happens to the lipids once they are inside the intestinal cells?
Fatty-acid-transport proteins (FATP) bring them to cytoplasmic face of smooth endoplasmic reticulum (SER) where triacyclglycerols are reformed from free fatty acids and monoacylglycerol
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Once triacylglycerols are reformed inside the intestinal cell, where do they go?
After transport into the lumen of the SER, the triacylglycerols associate with specific proteins and a small amount of phospholipid and cholesterol to form lipoprotein transport particles
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Where do chylomicrons end up?
Are released into the lymph system and then eventually into the blood so that triacyclglycerols can be absorbed by tissues
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Where will chylomicrons bind?
They bind to membrane-bound lipoprotein lipases
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Where will chylomicrons bind? What happens?
Primarily at adipose tissue and muscle; triacylglycerols are degraded again into free fatty acids and monoacylglycerols for transport into the tissue, are resynthesized, and stored
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Where can chylomicrons be oxidized? What does it provide?
In muscle and other tissues, can be oxidized to provide energy
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Chylomicrons also function in the transport of what 2 things?

1. Fat-soluble vitamins
2. Cholesterol
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Glycocholate
Responsible for the packing and unpacking of the vesicles; acts as a detergent to solubilize fats for absorption and is itself absorbed
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Micelle formation is facilitated by what?
Bile salts
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The structure of glycocholate resembles what?
Cholesterol
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Describe snake venom
A highly modified form of saliva, consists of 50 to 60 different protein and peptide components that differ among species of snake and possibly individuals of the same species
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Rattlesnake venom contains what 3 digestive enzymes?

1. Proteases like collagenase
2. Phospholipases
3. Other connective tissue digestive enzymes like hyaluronidase
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What are the 2 functions phospholipases in snake venom?
Digest cell membranes at the site of the snakebite to cause a loss of cellular components and
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Basement Membranes
A thin sheet of fibrous proteins, including collagen, that underlies the epithelial cells
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What 2 things are degraded by proteolytic enzymes in snake venom? What is the outcome?

1. Basement membranes
2. Components of the extracellular matrix

* Leads to severe tissue damage
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Some proteolytic enzymes in snake venom can stimulate what?
The formation of blood clots and enzymes that digest blood clots; depletes all clotting factors so clots can’t form
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What is a neurotoxic effect snake venom can have on prey?
Can immobilize them
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What are 3 pharmacological uses of snake venom? What species?

1. South african pit viper: hypertension drugs
2. Southeastern pigmy rattlesnake: reduce likelihood of heart attack
3. Copperhead: promising anticancer drug
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What is the function of collagenase in snake venom?
Digests the protein collagen, a major component of connective tissue
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What is the function of hyaluronidase in snake venom?
Digests hyaluronidase, a glycosaminoglycan component of connective tissue
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How do snakes begin digestion?
They inject digestive enzymes into the prospective meal before consumption
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Emulsion
A mixture of lipid droplets and water
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Bile Salts
Amphipathic molecules synthesized from cholesterol in the liver secreted from the gallbladder in response to cholecystokinin
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What do bile salts do?
Enhance emulsification after lipids leave the stomach
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Steatorrhea
When large amounts of fats (as much as 30g per day) are excreted in the feces because of inadequate production of bile salt due to liver disesase
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What is steatorrhea named after?
Stearic acid, a common fatty acid
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Energy meets what 3 fundamental needs

1. Muscle contraction: performance of mechanical work in muscle contraction and cellular movements
2. Active transport of molecules and ions
3. Synthesis of macromolecules and other biomolecules from simple precursors
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Phototrophs
Organisms that obtain energy by capturing sunlight
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Chemotrophs
Organisms that obtain energy through the oxidation of carbon fuels
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Metabolic Pathways
Molecules are degraded or synthesized stepwise in a series of reactions
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ATP can be called (1) and is formed by (2)\`

1. energy currency of life
2. the oxidation of carbon fuels
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What is common to all metabolic pathways despite many reactions occurring inside a cell?
A limited number of reaction types that involve particular intermediates
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Metabolic pathways are (1) regulated.

1. highly
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How are enzymes involved in metabolism organized?
Into large complexes
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Metabolism
A series of linked reactions that convert a specific reactant into a specific product
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Intermediary Metabolism
The entire set of cellular metabolic reactions
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Catabolic Pathways
Combustion of carbon fuels to synthesize ATP or ion gradients
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Anabolic Pathways
Using ATP and reducing power to synthesize large biomolecules
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Amphibolic Pathways
Pathways that can function anabolically or catabolically (ex. krebs cycle)
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What types of reactions are always distinct even when anabolic and catabolic pathways have some common reactions?
Irreversible reactions are always distinct
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Homeostasis
A stable biochemical environment maintained by careful regulation of biochemical processes
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What 3 regulatory controls are especially prominent in metabolic processes?

1. Amount of enzymes present
2. Catalytic activity of enzymes
3. The accessibility of substrates
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What 2 criteria must be met to construct a metabolic pathway?

1. Individual reactions must be specific
2. The pathway in total must be thermodynamically favorable
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What can you do if one reaction in a pathway is thermodynamically unfavorable?
Can be made to occur by coupling it to a more favorable reaction
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Energy derived from fuels or light is converted into what?
Adenosine triphosphate (ATP)
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Describe how its structure makes ATP energy rich.
Triphosphate unit containing 2 phosphoanhydride linkages makes it kinetically stable while thermodynamically unstable
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How is free energy liberated? What reactions does it drive?
ATP hydrolysis, used to drive reaction that are not spontaneous (ex. muscle contraction)
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ATP is formed from (1) and (2) when fuel molecules are oxidized in chemotrophs or when light is trapped by autotrophs

1. ADP
2. Pi
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What is the free energy of ATP + H2O → ADP + Pi?
\-30.5 kJmol^-1
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What is the free energy of ATP + H2O → AMP + Pi
45\.6 kJmol^1