Digestion and Absorption

1
Digestion and Absorption

• Digestion is the process in which complex food
  substances (carbohydrates, proteins, and lipids)
  are degraded to products that can be absorbed.
• Absorption (or uptake) of these products occur
  when they are transported into absorptive cells
  in the small intestine.

2
Organs

• Several major organs contribute to the digestion
  and absorption of food substances. They include
  the mouth, stomach, small intestine, liver,
  pancreas, and the gall bladder.
• Each organ is responsible for degrading and/or
  absorbing food substances. They contain enzymes
  and other substances that allow this process to
  occur.
• What breaks down where?
• Mouth- carbohydrates
• Stomach- proteins, lipids, (histones)
• Small intestine- proteins, lipids, and carbos, (
  nucleic acids).

3
Organs (Cont.)

• Which organ contains which enzyme (or
  substances)?
• Mouth- amylase, saliva, and mucins
• Stomach- HCl, pepsinogen (pepsin), gastric
  lipases, and mucins.
• Liver- Bile
• Gall Bladder- Bile (concentrated)
• Pancreas- pancreatic juices (ex. Lipases,
  peptidases, (chymo)trypsinogen, amylase, and
  etc)
• Small Intestine- Bile (from the gall bladder),
  pancreatic juices.

4
Secretagogues

• Secretogogues regulate substances secreted by the
  various digestive organs by acting on receptors
  to certain cells.
• Three types of secretogogues
• 1.) Neurotransmitters-
• acetylcholine (salivary, gastric, pancreatic
  secretions)
• 2.) Biogenic amines-
• histamine (stimulates HCl secretion in stomach)
• 3.) Hormones-
• aldosterone (electrolyte composition of saliva)
• gastrin (stimulates HCl and pepsinogen)
• cholecystokinin (gall bladder contraction,
  pancreatic secretions, inhibits gastric
  motility)

5
Secretagogues (cont.)

• Secretin (helps neutralize stomach acids by
  stimulating pancreatic secretion of NaHCO3)
• vasoactive intestional peptide (VIP)
  (stimulates NaCl secretion in small intestine)
• Question Would a combination of gastrin
  inhibition and the presence of a histamine analog
  cause an increase or decrease in stomach pH?
• Ans Increase. Inhibition of gastrin and
  histamine lead to decreased HCl production.

6
Carbohydrate digestion absorption

• Carbohydrate digestion involves the enzymatic
  degradation of di-, tri, and polysaccharides to
  monosaccharides (glucose, fructose, galactose).
• Digestion begins in the mouth with salivary
  amylase (hydrolyzes ? 1-4 bonds).
• Polysaccharides are then further broken down by
  pancreatic amylase ( also hydrolyzes ? 1-4 bonds)
  in the small intestine.
• Final degradation occurs on the surface
  (brushborder) of the absorptive cells in the
  jejunum. The brushborder secretes
  amylo-1,6-glucosidase (hydrolyze ? 1-6 bonds),
  lactase, sucrase, and maltase.

7
Carbohydrate digestion absorption (cont.)

• Once carbohydrates are broken down into
  monosaccharides, the are then absorbed into the
  intestinal cells by facilitated (membrane
  carrier) or active transport (membrane carrier,
  Na, and ATP).
• Fructose facilitative transport
• Glucose and galactose active transport
• Lactose intolerance Caused by deficiency in
  lactase. Lactose is not hydrolyzed and
  accumulates in the intestine where it is
  fermented by intestinal microorganisms.

8
Carbohydrate digestion absorption (cont.) and
Protein digestion absorption

• Question How would a deficiency in
  amylo-1,6-glucosidase effect carbohydrate
  absorption?
• Ans. Any polysaccharide containing an ? 1-6 bond
  will not be hydrolyzed and therefore will not be
  absorbed by the intestinal cells.
• Protein digestion involves the enzymatic
  degradation of proteins to amino acids, di-, or
  tri- peptides.
• Digestion begins in the stomach with the
  interaction with pepsin (active form of
  pepsinogen which is cleaved by HCl).

9
Protein digestion absorption (cont.)

• Further proteolytic cleavage occurs in the
  intestinal lumen by pancreatic trypsin,
  chymotrypsin, elastase, and carboxy peptidases.
  These enzymes are only active in the intestine
  and are activated by trypsin.
• Trypsin is activated by enteropeptidase and
  trypsin.
• Final degradation occurs on the membrane of the
  intestinal microvilli by the action of
  aminopeptidases.
• Carboxypeptidases and aminopeptidases
  exopeptidases
• Endopeptidases trypsin, chymotrypsin, and
  elastase.
• Protein absorption occurs through active
  transport.

10
Protein digestion absorption (cont.)

• Question How would a significant decrease in
  trypsin production effect overall protein
  digestion and absorption?
• Ans. A significant decrease in trypsin will lead
  to a decrease in protein digestion and absorption
  because trypsin is the key enzyme that is
  responsible for activating pancreatic proteases.

11
Lipid digestion and absorption

• Lipid digestion is the enzymatic degradation of
  fats (TAGs) to monoacylglycerols and fatty
  acids.
• Degradation (lipolysis) begins in the stomach
  with (slow acting) gastric lipases.
• Pancreatic lipases and bile are mixed with
  hydrolyzed product (TAG) in the duodenum. The
  bile emulsifies the fat into fat droplets
  (miscelles) while the action of colipase and
  pancreatic lipase act on the product to produce
  monoacylglycerol and 2 fatty acid chains.
• Monoacylglycerol and long chain fatty acids are
  packaged into mixed micelles (cholesterol, bile
  salts, and fat soluble vitamins) and diffuse
  across the cellular membrane (of the jejunum).
• Fatty acids with 10 carbon atoms are absorbed
  across the membrane without mixed micelle
  formation.

12
Nucleic Acid digestion and Absorption

• Nucleic acid digestion occurs when DNA or RNA is
  degraded to nucleosides
• Occurs in the duodenum where diesterases
  hydrolyzes oligonucleotides to monononucleotides
  and phosphatase hydrolyzes mononucleotides to
  nucleotides.
• Passive diffusion
• Question Will a significant decrease in colipase
  cause an increase or decrease in the hydrolysis
  of TAG to monoacylglycerol and 2 fatty acids?
• Ans Decrease. Colipase is responsible for
  stabilizing pancreatic lipase in the fat droplet
  which will allow TAG hydrolysis to occur.

13
Basic Concepts of Metabolism

• Metabolism consists of two types of reactions
  Catabolism Anabolism
• Catabolism Process in which macromolecules are
  broken up to yield energy and simple organic
  compounds. Catabolic reactions mainly involve
  oxidative degradation.
• Anabolism Process in which simple organic
  compounds and energy are used to form
  macromolecules. Anabolic reactions mainly involve
  reductive biosyntheses.
• Free Energy the energy that is capable of doing
  work at a constant temperature and pressure.

14
Basic Concepts of Metabolism

• Free Energy that is utilized by an organism is in
  the form of free energy Carriers ATP, NADH,
  NADPH, FADH2, and CoA.
• ATP is the universal energy carrier. Its
  synthesized during glucose metabolism and is used
  to maintain homeostasis (muscle contraction,
  active transport, anabolic processes, and signal
  transduction).
• ATP Structure consists of an adenine base, a
  ribose sugar, a negatively charged triphosphate
  group.
• The triphosphate group contains 2
  phosphoanhydride bonds which give ATP its high
  energy characteristic.
• These anhydride bonds are unstable and require a
  Mg2 cation to stabilize ATP.
• Mg2 cation is used to prevent electrostatic
  repulsion between negatively charged phosphate
  groups.

15
Basic Concepts of Metabolism

• ATP hydrolysis to ADP Pi occurs at the ?
  phosphoanhydride bond and yields a free energy of
  7.3 kcal/mol. This is a thermodynamically
  favorably reaction, so the ?G will be -7.3
  kcal/mol. Remember, the (-) sign is used to
  signify that the reaction is thermodynamically
  favorable.
• ATP, when compared to other high energy
  molecules, has an intermediate position when it
  comes to the amount of free energy released. As a
  result, ATP can function as the principle
  phosphate donor and ADP can function as the
  principle phosphate acceptor.

16
Basic Concepts of Metabolism

• Question
• Acetyl phosphate H2O gt Acetyl Pi ?G
  -10.3 kcal/mol
• ADP Pi gt ATP H2O ?G 7.3
  kcal/mol
• Acetyl Phosphate ADP gt Acetyl ATP ?G -3.0
  Kcal/mol
  Thermodynamically favorable

17
Basic Concepts of Metabolism

• NADH and FADH2 are electron carriers during the
  oxidation of fuel molecules.
• During oxidation, NAD and FAD is reduced whereby
  NAD accepts 1 H and 2 e- and FAD accepts 2 H and
  2e-.
• Active site of reduction on NAD is at the
  nicotinamide ring and for FAD, the flavin ring.
• These two e- carriers will transfer eventually
  transfer their electrons to O2 in the e-
  transport chain which will ultimately lead to ATP
  production.
• NADPH is similar to NADH in structure (except for
  the phosphate group at the second carbon of the
  ribose sugar). NADPH however is involved in
  biosynthetic (reductive) pathways as an electron
  donor.

18
Basic Concepts of Metabolism

• CoA is an acyl or acetyl carrier. The active site
  for CoA is the sulfhydryl (SH) group located at
  the end of the ?-Mercaptoethylamine unit.
• Question
• NAD and FAD are_________(oxidized, reduced)
  during various catabolic pathways?

19
Glycolysis

• Glycolysis is the major pathway of glucose
  metabolism. It is the process in which glucose (6
  C molecule) is degraded into two 3 C molecules.
• This pathway occurs in the cytoplasm of the cell
  and is an anaerobic process in itself. The
  products, however can be utilized under both
  aerobic and anaerobic conditions.
• In anaerobic conditions, the final product is 2
  molecules of Lactate and for aerobic conditions,
  2 molecules of pyruvate are produced.
• Conditions in which glycolysis products are used
  anaerobically include microorganisms, during
  increased glycolysis where the e- transport chain
  is saturated with reducing equivalents, and
  occasionally in muscle cells during extreme
  exercise.

20
Glycolysis

• Glycolysis yields a net gain of 2 ATP and
  produces 2 molecules of NADH. These two NADH
  molecules can either be used in conjunction with
  LDH to produce lactate under anaerobic conditions
  or enter the mitochondria through the
  glycerol-3,P-shuttle under aerobic conditions to
  regenerate NAD.
• Question What would a eukaryotic cell do if it
  were unable to regenerate NAD through the
  glycerol phosphate shuttle?
• Ans It would utilize the anaerobic pathway to
  regenerate NAD.

21
Glycolysis

• There are three reactions in the glycolytic
  pathway that are irreversible. This
  irreversibility is mainly due to a high negative
  ?G value in the three reactions.
• hexokinase (or glucokinase)
• Glucose ATP -----------gtGlu-6-P ADP
• high Glu-6-P can cause inhibition
• not the committed step (intermediate in glycogen
  biosynthesis)
• PFK
• Fructose-6-P ATP----gtFructose-1,6-bisphosphate
  ADP
• Committed step
• PFK is inhibited by high ATP and
  citrate.

22
Glycolysis

• Pyruvate Kinase
• PEP ADP -------gt Pyruvate ATP
• Inhibited by high ATP
• not rate limiting (used in amino acid
  biosynthesis)
• Its also important to know which steps yield ATP
  and NADH. The steps that result in the formation
  of 3-phosphoglycerate and pyruvate yield ATP and
  the formation of 1,3-bisphosphoglycerate yield
  NADH.
• Question What enzyme is responsible for
  converting fructose-6-p to dihydroxyacetone-P
  and/or Glyceraldehyde-3-p? How many carbon
  molecules does the substrate have? Products?
• Ans Aldolase. 6. 3