Intro to intermediary metabolism week 1 Flashcards
metabolism
intermediary metabolism
Metabolism is the sum of the chemical reactions that occur in a cell, a tissue or in the body. Metabolism is built by pathways that are purposeful sequences of enzymes to convert substrates to end-products through multiple enzymatic reactions.
The purpose of the intermediary metabolism is to generate energy from fuel molecules to feed all cells of the body. Some of the pathways are catabolic to break down fuel molecules and some of them are anabolic to produce fuel molecules when needed. In addition, special pathways synthesize and break down biomolecules necessary for normal functioning of the body.
Catabolism
discuss types of molecules involved, whether ender- or exergonic, purpose of these types of rxns
Catabolism: oxidative degradation of complex nutrient molecules (carbohydrates, lipids and proteins) obtained either from the environment, or from cellular reserves. The breakdown of these molecules by catabolism leads to the formation of simpler molecules such as lactic acid, ethanol, carbon dioxide, urea, or ammonia. Catabolic reactions are usually exergonic (release of energy), and often the chemical energy released is captured in the form of reduced coenzymes (NADH and FADH) that carry the energy forward to form ATP (Adenosine Triphosphate).
- GI tract: Take up and digest nutrient macromolecules and absorb building blocks
Proteins: 20 amino acids
Polysaccharides: carbohydrate units convertible to glucose
Lipids: glycerol + fatty acids (components of special lipids) - Within cells: Building blocks are further degraded to yield a limited set of simpler metabolic intermediates.
Amino acids –> Alpha-keto-acids –> TCA intermediates
–>pyruvate–> AcCoA
–>acetyl group of AcCoA
Glucose and glycerol–> pyruvate –> AcCoA
Fatty acids –> AcCoA
3. Mitochondria: Energy generation:
AcCoA processed in TCA + oxidative phosphorylation –> CO2 + H2O + energy (of reduced cofactors) (ATP)
Anabolism
discuss types of molecules involved, whether ender- or exergonic, purpose of these types of rxns
Anabolism: a synthetic process in which the varied and complex biomolecules (proteins, nucleic acids, polysaccharides, and lipids) are assembled from simpler precursors. It involves the formation of new covalent bonds. Input of chemical energy (mostly from ATP) is necessary to drive these endergonic (need energy) reactions.
Anabolism of biomolecules
In various cell compartments:
1. Utilization of building blocks to store energy (glycogen, triglycerides)
2. Processing of building blocks to generate other important biomolecules (complex carbohydrates, nucleic acids, lipids,etc)
3. Utilization of small-molecular weight intermediates to build biomolecules (glucose, fatty acid and amino acid synthesis)
Digestion and absorption of food takes place in the GI tract which contains what 3 “major players”?
- organs and specialized glands
- special enzymes and biomolecules
- surface epithelia
Name the functions of the following organs:
salivary glands
stomach
pancreas
liver
gallbladder
small intestine
large intestine
salivary glands: produces fluid and digestive enzymes
stomach: produces HCl and digestive enzymes
pancreas: produces NaHCO3 and intralumenal digestive enzymes
liver: produces bile salts
gallbladder: storage and concentration of bile
small intestine: terminal food digestion, absorption of nutrients and electrolytes
large intestine: absorption of electrolytes
The mechanical action of chewing and stomach churning converts food into small particles called ____.
chyme
Where in the GI tract does digestion of foodstuffs begin?
starts in the mouth (carbs) or in the stomach (lipids, proteins)
Where in the GI tract does most digestion and absorption occur?
After digestion, how do nutrients enter the body? How do fats enter the body?
- small intestine. note absorption is by epithelial cells. see pg 21 of course notes
- Once digested, nutrients enter the hepatic portal vein and travel to the liver and then through the blood to the rest of the body. However, most fats bypass the liver and are taken up by the lymphatic circulation and delivered to the bloodstream. Lipids being apolar, need specific vehicles (lipoproteins) for transportation.
What 2 types of enzymes degrade proteins?
Proteins are degraded by endopeptidases (internal cleavage of large fragments) and exopeptidases (1 amino acid at a time off ends), carboxypeptidases (COOH end) or aminopeptidases (NH2 end).
Describe the gastric phase, pancreatic phase, and intestinal phase of the digestion and aborption of proteins. Be sure to name cell types and enzymes involved along with their products.
What role do epithelial cells play?
Gastric phase: The stomach contains gastric juice with HCl (pH < 2) and members of the pepsin protease family (secreted as a zymogen, pepsinogen). Pepsin releases large peptide products and some amino acids, which stimulates the release of cholecystokinin (CCK) from intestinal endocrine cells and initiates the pancreatic phase of digestion. There is also precipitation which allows for easier degradation of proteins by enzymes.
Pancreatic phase: Pancreas is the major organ that synthesizes and secretes large amounts of enzymes needed for digestion. Pancreas is composed of two histologically distinct tissue types with two functions. The endocrine pancreas made up of islets of Langerhans and releases insulin, glucagon and other hormones into the bloodstream. The exocrine pancreas plays an essential role in digestion. It secretes about 1.5 L of pancreatic juice containing 0.115 M NaHCO3 at pH 8, and hydrolytic enzymes (trypsin, chymotrypsin, elastase, carboxypeptidase A and B in zymogen forms that are activated in the small intestine, which is initiated by enteropeptidase) into the duodenum each day. The enzymes released from the pancreas only function at a neutral pH, hence the release of bicarbonate.
We already said that peptides and amino acids stimulate intestinal endocrine cells to release CCK. CCK stimulates the intestinal mucosa to release enteropeptidase. Both CCK and secretin stimulate pancreatic acinar cells to release trypsinogen. Enteropeptidase activates trypsinogen and turns it into trypsin. Trypsin is a key enzyme because it activates all of the other zymogens released by the pancreas. Trypsin activates the following enzymes:
chymotrypsinogen—>chymotrypsin
proelastase–>elastase
procarboxypeptidase—>carboxypeptidase
The products of these enzymes are small peptides and some amino acids.
The epithelial cells lining the surface of the intestinal lumen have endo-and aminopeptidase activities, which further degrade the peptides to amino acids which are then absorbed by amino acid or peptide transport systems. There are a number of brush border specific transport systems for the uptake of different amino acids.
see slide 12 of notes
Dietary carbohydrates (mono-,di-, and polysaccharides) provide the major portion of our daily caloric requirement. Describe the oral, pancreatic, and intestinal phases of digestion and what enzymes are implicated (also indicate products). Discuss epithelial cell involvment.
What happens to oligosacchardes not hydrolyzed by the digestive system?
Oral phase: Starch and glycogen are partially degraded by the enzyme α-amylase, which is present in saliva. The products are glucose, disaccharides and trisaccharides.
Note that there is no digestion of carbs in the stomach.
Pancreatic phase: α-amylase is also secreted by the pancreas. the products are glucose, disaccharides, and trisaccharides.
Intestinal phase: major and final digestion, absorption. Oligosaccharides by α-amylase
Products: glucose, di- and trisaccharides
Why is the same enzyme secreted in the mouth and from the pancreas?
- alpha-amylase is deactivated after reaching the stomach
- food does not stay in mouth long enough to be fully digested by oral alpha-amylase
Intestinal cells (epithelium): Further digestion of these oligosaccharides occurs on the surface of the intestinal cells by α-glucosidase. Specific disaccharides, lactose and sucrose are digested by lactase and sucrase. Monosaccharides are absorbed by mucosal cells.
Oligosaccharides not hydrolyzed by amylase or the intestinal surface enzymes reach the lower ileum where bacteria, with a greater range of saccharidases, metabolize the sugars anaerobically to produce short –chain fatty acids, lactate, H2, methane and CO2 (gas!)
The majority of dietary fat is composed in what 3 forms?
- triglycerides (TGs)
- cholesterol
- phospholipids
What form are lipids found in the oral phase?
Describe the gastric, liver and gallbladder, pancreas, and intestinal phases of the digestion of lipids. Be sure to discuss cell types and enzymes involved as well as products formed.
How are lipids absorbed?
Because lipids are water-insoluble, fat is present in the oral phase as a fat droplet-water emulsion.
Gastric phase: digestion of TGs starts in the stomach by lingual and gastric lipases. Lipid droplets result.
Pancreatic phase: Pancreatic juice contains an unspecific lipid esterase, which acts on cholesterol esters, monoglycerides and other lipid esters. It also contains phospholipase A2 to help the digestion of phospholipids. The important enzyme in the digestion of triglycerides is pancreatic lipase. This enzyme is anchored to the surface of fat droplets by a pancreatic protein called colipase and cleaves two fatty acids from each triglyceride to yield a 2-monoglyceride.
To be absorbed by the mucosal cells these processed fats must interact with bile salts. Bile salts, synthesized by the liver and released by the gall bladder, act like detergents to solubilize fatty acids and monoglycerides, cholesterol, dietary lysophospholipids and fat-soluble vitamins, and form mixed micelles. The micelles transport these lipids through the chyme to the surface of the enterocytes where the micelles disaggregate and lipids enter the cells by passive diffusion. The bile salts (that are released in the lumen when fats are absorbed) are reabsorbed in the small intestine by the level of the ileum, so they participate in cycles of micelle formation. In the mucosal cells, triglycerides are resynthesized from the fatty acids (only > 10-12 carbon) and cholesterol is re-esterified with fatty acids. The triglycerides, cholesterol esters and phospholipids are packaged in lipoprotein particles, so-called chylomicrons, for delivery to the lymphatic system and then to the blood. However, fatty acids shorter than 10 carbons are released into the hepatic portal vein and enter the general circulation bound to albumin.
How are nutrients transported in blood? Taken up by cells?
How do cells manage the conflicting demands of catabolism and anabolism?
- The cell maintains tight and separate regulation of both catabolism and anabolism, so that metabolic needs are served in an immediate and orderly fashion.
a. Fuel molecules are degraded only at the rate necessary to satisfy the cell’s need for reducing power (NADH2/NAD) and phosphorylation potential (ATP/ADP+Pi).
b. Biosynthetic activity is matched to cellular demands for essential biomolecules; any excess intermediates are stored as fat or polysaccharides (nucleotides, RNA, DNA, and protein are synthesized according to the needs of the cell; they are not stored).
