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The Digestive System and Metabolism
Muse 2440lecture #11digestion II6/15/10
The Pancreas
Pancreatic Enzymes Pancreatic alpha-amylase
A carbohydrase
Breaks down starches
Similar to salivary amylase
Pancreatic lipase Breaks down complex lipids
Releases products (e.g., fatty acids) that are easily absorbed
The Pancreas
Pancreatic Enzymes Nucleases
Break down nucleic acids
Proteolytic enzymes Break certain proteins apart
Proteases break large protein complexes
Peptidases break small peptides into amino acids
70% of all pancreatic enzyme production
Secreted as inactive proenzymes
Activated after reaching small intestine
The Liver
Is the largest visceral organ (1.5 kg; 3.3 lb)
Lies in right hypochondriac and epigastric
regions
Extends to left hypochondriac and umbilical
regions
Performs essential metabolic and synthetic
functions
The Liver
Anatomy of the Liver
Is wrapped in tough fibrous capsule
Is covered by visceral peritoneum
Is divided into lobes
The Liver
Figure 24–19a The Anatomy of the Liver.
The Liver
Figure 24–19b, c The Anatomy of the Liver.
The Liver
Hepatic Blood Supply
1/3 of blood supply Arterial blood from hepatic artery proper
2/3 venous blood from hepatic portal vein,
originating at Esophagus
Stomach
Small intestine
Most of large intestine
The Liver
Hepatocytes Are liver cells Adjust circulating levels of nutrients
Through selective absorption and secretion
In a liver lobule form a series of irregular plates arranged like wheel spokes
Many Kupffer cells (stellate reticuloendothelial cells) are located in sinusoidal lining
As blood flows through sinusoids Hepatocytes absorb solutes from plasma And secrete materials such as plasma proteins
The Liver
The Bile Duct System
Liver secretes bile fluid
Into a network of narrow channels (bile canaliculi)
Between opposing membranes of adjacent liver
cells
The Liver
Right and Left Hepatic Ducts
Collect bile from all bile ducts of liver lobes
Unite to form common hepatic duct that leaves the
liver
Bile Flow
From common hepatic duct to either
The common bile duct, which empties into duodenal ampulla
The cystic duct, which leads to gallbladder
The Liver
The Common Bile Duct
Is formed by union of Cystic duct
Common hepatic duct
Passes within the lesser omentum toward
stomach
Penetrates wall of duodenum
Meets pancreatic duct at duodenal ampulla
The Liver
Figure 24–21 The Gallbladder and Bile Ducts.
The Liver
The Physiology of the Liver
1. Metabolic regulation
2. Hematological regulation
3. Bile production
The Liver
Metabolic Regulation
The liver regulates:
1. Composition of circulating blood
2. Nutrient metabolism
3. Waste product removal
4. Nutrient storage
5. Drug inactivation
The Liver
Hematological Regulation
Largest blood reservoir in the body
Receives 25% of cardiac output
Coordination of Secretion and Absorption
Secretin Is released when chyme arrives in duodenum Increases secretion of bile and buffers by liver and
pancreas
Cholecystokinin (CCK) Is secreted in duodenum
When chyme contains lipids and partially digested proteins
Accelerates pancreatic production and secretion of digestive enzymes
Relaxes hepatopancreatic sphincter and gallbladder Ejecting bile and pancreatic juice into duodenum
Coordination of Secretion and Absorption
Gastric Inhibitory Peptide (GIP)
Is secreted when fats and carbohydrates enter
small intestine
Vasoactive Intestinal Peptide (VIP)
Stimulates secretion of intestinal glands
Dilates regional capillaries
Inhibits acid production in stomach
Coordination of Secretion and Absorption
Gastrin Is secreted by G cells in duodenum
When exposed to incompletely digested proteins
Promotes increased stomach motility
Stimulates acids and enzyme production
Enterocrinin Is released when chyme enters small intestine
Stimulates mucin production by submucosal glands of duodenum
Coordination of Secretion and Absorption
Figure 24–22 The Activities of Major Digestive Tract Hormones.
Coordination of Secretion and Absorption
Intestinal Absorption
It takes about 5 hours for materials
to pass from duodenum to end of ileum
Movements of the mucosa increases
absorptive effectiveness
Stir and mix intestinal contents
Constantly change environment around epithelial
cells
The Large Intestine
Functions of the Large Intestine
Reabsorption of water
Compaction of intestinal contents into feces
Absorption of important vitamins produced by
bacteria
Storage of fecal material prior to defecation
The Large Intestine
Figure 24–23a The Gross Anatomy and Regions of the Large Intestine.
The Large Intestine
Histology of the Large Intestine
Lack villi
Abundance of mucous cells
Presence of distinctive intestinal glands
Are deeper than glands of small intestine
Are dominated by mucous cells
The Large Intestine
Three Vitamins Produced in the Large Intestine
1. Vitamin K (fat soluble):
Required by liver for synthesizing four clotting factors,
including prothrombin
2. Biotin (water soluble):
Important in glucose metabolism
3. Pantothenic acid: B5 (water soluble):
Required in manufacture of steroid hormones and some
neurotransmitters
Digestion
Essential Nutrients
A typical meal contains
Carbohydrates
Proteins
Lipids
Water
Electrolytes
Vitamins
Digestion
Figure 24–26 A Summary of the Chemical Events in Digestion.
Digestion
Vitamins are organic compounds required
in very small quantities
Are divided in two major groups:
Fat-soluble vitamins
Water-soluble vitamins
Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Introduction to Metabolism
Cells break down organic molecules to
obtain energy
Used to generate ATP
Most energy production takes place in
mitochondria
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Metabolism
The Nutrient Pool
Contains all organic building blocks cell needs
To provide energy
To create new cellular components
Is source of substrates for catabolism and
anabolism
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Metabolism
Catabolism
Is the breakdown of organic substrates
Releases energy used to synthesize high-energy
compounds (e.g., ATP)
Anabolism
Is the synthesis of new organic molecules
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Metabolism
In energy terms
Anabolism is an “uphill” process that forms
new chemical bonds
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Metabolism
Organic Compounds Glycogen
Most abundant storage carbohydrate A branched chain of glucose molecules
Triglycerides Most abundant storage lipids Primarily of fatty acids
Proteins Most abundant organic components in body Perform many vital cellular functions
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Metabolism
Figure 25–2 Nutrient Use in Cellular Metabolism.
Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin CummingsFigure 24.3
Stage 1 Digestion in GI tract lumen to absorbable forms.Transport via blood totissue cells.
Stage 2 Anabolism (incorporation into molecules) and catabolism of nutrients to form intermediates within tissue cells.
Stage 3 Oxidative breakdown of products of stage 2 in mitochondria of tissue cells. CO2 is liberated, and H atoms removed are ultimately delivered to molecular oxygen, formingwater. Some energy released isused to form ATP.
Catabolic reactionsAnabolic reactions
Glycogen
PROTEINS
Proteins Fats
CARBOHYDRATES
Glucose
FATS
Amino acids Glucose and other sugars Glycerol Fatty acids
Pyruvic acid
Acetyl CoA
Infrequent CO2
NH3
H
Krebscycle
Oxidativephosphorylation
(in electron transport chain)
O2
H2O
Overview of metabolic processes
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Carbohydrate Metabolism
Generates ATP and other high-energy
compounds by breaking down
carbohydrates:
glucose + oxygen carbon dioxide + water
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Carbohydrate Metabolism
Glucose Breakdown Occurs in small steps
Which release energy to convert ADP to ATP
One molecule of glucose nets 36 molecules of ATP Glycolysis
Breaks down glucose in cytosol into smaller molecules used by mitochondria
Does not require oxygen: anaerobic reaction
Aerobic Reactions Also called aerobic metabolism or cellular respiration Occur in mitochondria, consume oxygen, and produce ATP
Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin CummingsFigure 24.5
Via oxidativephosphorylationVia substrate-level
phosphorylation
MitochondrionMitochondrialcristaeCytosol
KrebscycleGlucose
Glycolysis
Pyruvicacid
Electron transportchain and oxidativephosphorylation
Chemical energy (high-energy electrons)
1 During glycolysis, each glucose molecule is broken down into two molecules of pyruvic acid in the cytosol.
2 The pyruvic acid then enters the mitochondrial matrix, where the Krebs cycle decomposes it to CO2. During glycolysis and the Krebs cycle, small amounts of ATP are formed by substrate-level phosphorylation.
3 Energy-rich electrons picked up bycoenzymes are transferred to the elec-tron transport chain, built into the cristae membrane. The electron transport chain carries out oxidative phosphorylation, which accounts for most of the ATP generated by cellular respiration.
Chemical energy
Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Carbohydrate Metabolism
Glycolysis
Breaks 6-carbon glucose
Into two 3-carbon pyruvic acid
Pyruvate
Ionized form of pyruvic acid
Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin CummingsFigure 24.4a
Enzyme
Catalysis
Enzyme
(a) Substrate-level phosphorylation
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Carbohydrate Metabolism
Figure 25–3 Glycolysis.
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Carbohydrate Metabolism
Mitochondrial Membranes Outer membrane
Contains large-diameter pores
Permeable to ions and small organic molecules (pyruvic
acid)
Inner membrane Contains carrier protein
Moves pyruvic acid into mitochondrial matrix
Intermembrane space Separates outer and inner membranes
The TCA Cycle
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Carbohydrate Metabolism
The TCA Cycle (citric acid cycle) The function of the citric acid cycle is
To remove hydrogen atoms from organic molecules and
transfer them to coenzymes
In the mitochondrion Pyruvic acid reacts with NAD and coenzyme A (CoA)
Producing 1 CO2, 1 NADH, 1 acetyl-CoA
Acetyl group transfers From acetyl-CoA to oxaloacetic acid
Produces citric acid
Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin CummingsFigure 24.7
Krebs cycle
NAD+
NAD+
GDP +
NAD+
FAD
NAD+
NADH+H+
Cytosol
Mitochondrion(matrix)
NADH+H+
FADH2
NADH+H+
Citric acid
(initial reactant)
Isocitric acid
Oxaloacetic acid
(pickup molecule)
Malic acid
Succinic acidSuccinyl-CoA
GTP
ADP
Carbon atom
Inorganic phosphate
Coenzyme A
Acetyl CoA
Pyruvic acid from glycolysis
Transitionalphase
Fumaric acid
NADH+H+
CO2
CO2
CO2
-Ketoglutaric acid
Electron trans-port chain and oxidativephosphorylation
Glycolysis Krebscycle
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Carbohydrate Metabolism
The TCA Cycle
CoA is released to bind another acetyl group
One TCA cycle removes two carbon atoms
Regenerating 4-carbon chain
Several steps involve more than one reaction or enzyme
H2O molecules are tied up in two steps
CO2 is a waste product
The product of one TCA cycle is
One molecule of GTP (guanosine triphosphate)
Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Carbohydrate Metabolism
Summary: The TCA Cycle
CH3CO - CoA + 3NAD + FAD + GDP + Pi + 2 H2O
CoA + 2 CO2 + 3NADH + FADH2 + 2 H+ + GTP
Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Carbohydrate Metabolism
Oxidative Phosphorylation and the ETS
Is the generation of ATP
Within mitochondria
In a reaction requiring coenzymes and oxygen
Produces more than 90% of ATP used by
body
Results in 2 H2 + O2 2 H2O
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Carbohydrate Metabolism
The Electron Transport System (ETS)
Is the key reaction in oxidative
phosphorylation
Is in inner mitochondrial membrane
Electrons carry chemical energy
Within a series of integral and peripheral proteins
Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin CummingsFigure 24.9
Glycolysis Krebscycle
Electron trans-port chain and oxidativephosphorylation
EnzymeComplex I
EnzymeComplex III
EnzymeComplex IV
EnzymeComplex II
NADH+H+
FADH2
Fre
e e
nerg
y r
ela
tive t
o O
2 (
kcal/
mol)
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Carbohydrate Metabolism
Oxidation and Reduction
Oxidation (loss of electrons)
Electron donor is oxidized
Reduction (gain of electrons)
Electron recipient is reduced
The two reactions are always paired
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Carbohydrate Metabolism
Energy Transfer
Electrons transfer energy
Energy performs physical or chemical work (ATP
formation)
Electrons
Travel through series of oxidation–reduction reactions
Ultimately combine with oxygen to form water
Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin CummingsFigure 24.4b
ADP +
Membrane
High H+ concentration inintermembrane space
Low H+ concentration in mitochondrial matrix
Energyfrom food
Protonpumps
(electrontransport
chain)
ATPsynthase
(b) Oxidative phosphorylation
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Carbohydrate Metabolism
Coenzyme FAD
Accepts two hydrogen atoms from TCA cycle:
Gaining two electrons
Coenzyme NAD
Accepts two hydrogen atoms
Gains two electrons
Releases one proton
Forms NADH + H+
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Carbohydrate Metabolism
Figure 25–5b Oxidative Phosphorylation.
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Carbohydrate Metabolism
ATP Generation and the ETS Does not produce ATP directly
Creates steep concentration gradient across inner
mitochondrial membrane
Electrons along ETS release energy As they pass from coenzyme to cytochrome
And from cytochrome to cytochrome
Energy released drives H ion (H+) pumps That move H+ from mitochondrial matrix
Into intermembrane space
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Carbohydrate Metabolism
Chemiosmosis
Also called chemiosmotic phosphorylation
Ion channels and coupling factors use kinetic
energy of hydrogen ions to generate ATP
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Carbohydrate Metabolism
Summary: ATP Production
For one glucose molecule processed, cell gains 36
molecules of ATP
2 from glycolysis
4 from NADH generated in glycolysis
2 from TCA cycle (through GTP)
28 from ETS
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Carbohydrate Metabolism
Figure 25–6 A Summary of the Energy Yield of Aerobic Metabolism.
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Carbohydrate Metabolism
Gluconeogenesis
Is the synthesis of glucose from noncarbohydrate
precursors
Lactic acid
Glycerol
Amino acids
Stores glucose as glycogen in liver and skeletal
muscle
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Carbohydrate Metabolism
Glycogenesis
Is the formation of glycogen from glucose
Occurs slowly
Requires high-energy compound uridine
triphosphate (UTP)
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Carbohydrate Metabolism
Glycogenolysis
Is the breakdown of glycogen
Occurs quickly
Involves a single enzymatic step
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Lipid Metabolism
Lipid Catabolism
Enzymes in cytosol convert glycerol to pyruvic
acid
Pyruvic acid enters TCA cycle
Different enzymes convert fatty acids to
acetyl-CoA (beta-oxidation)
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Lipid Metabolism
Beta-Oxidation
A series of reactions
Breaks fatty acid molecules into 2-carbon fragments
Occurs inside mitochondria
Each step
Generates molecules of acetyl-CoA and NADH
Leaves a shorter carbon chain bound to coenzyme A
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Lipid Metabolism
Figure 25–8 Beta-Oxidation.
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Lipid Metabolism
Free Fatty Acids
Are an important energy source
During periods of starvation
When glucose supplies are limited
Liver cells, cardiac muscle cells, skeletal
muscle fibers, and so forth
Metabolize free fatty acids
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Lipid Metabolism
Lipoproteins Are lipid–protein complexes
Contain large insoluble glycerides and cholesterol
Five classes of lipoproteins Chylomicrons
Very low-density lipoproteins (VLDLs)
Intermediate-density lipoproteins (IDLs)
Low-density lipoproteins (LDLs)
High-density lipoproteins (HDLs)
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Lipid Metabolism
Chylomicrons
Are produced in intestinal tract
Are too large to diffuse across capillary wall
Enter lymphatic capillaries
Travel through thoracic duct
To venous circulation and systemic arteries
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Protein Metabolism
The body synthesizes 100,000 to 140,000
proteins
Each with different form, function, and structure
All proteins are built from the 20 amino acids
Cellular proteins are recycled in cytosol
Peptide bonds are broken
Free amino acids are used in new proteins
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Protein Metabolism
Amino Acid Catabolism
Removal of amino group by transamination
or deamination
Requires coenzyme derivative of vitamin B6
(pyridoxine)
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Protein Metabolism
Transamination
Attaches amino group of amino acid
To keto acid
Converts keto acid into amino acid
That leaves mitochondrion and enters cytosol
Available for protein synthesis
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Protein Metabolism
Deamination
Prepares amino acid for breakdown in TCA
cycle
Removes amino group and hydrogen atom
Reaction generates ammonium ion
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Protein Metabolism
Figure 25–10a Amino Acid Catabolism.
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Protein Metabolism
Figure 25–10b Amino Acid Catabolism.
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Protein Metabolism
Ammonium Ions
Are highly toxic, even in low concentrations
Liver cells (primary sites of deamination) have
enzymes that use ammonium ions to
synthesize urea (water-soluble compound
excreted in urine)
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Protein Metabolism
Figure 25–10c Amino Acid Catabolism.
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Protein Metabolism
Three Factors Against Protein Catabolism
Proteins are more difficult to break apart than
complex carbohydrates or lipids
A byproduct, ammonium ion, is toxic to cells
Proteins form the most important structural
and functional components of cells
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Protein Metabolism
Figure 25–11 Animation.
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Protein Metabolism
Figure 25–12 A Summary of the Pathways of Catabolism and Anabolism.
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Absorptive and Postabsorptive States
Five Metabolic Tissues
Liver
Adipose tissue
Skeletal muscle
Neural tissue
Other peripheral tissues
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Absorptive and Postabsorptive States
The Absorptive State Is the period following a meal when nutrient
absorption is under way
The Postabsorptive State Is the period when nutrient absorption is not under
way
Body relies on internal energy reserves for energy demands
Liver cells conserve glucose Break down lipids and amino acids
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Nutrition
Fat-Soluble Vitamins
Vitamins A, D, E, and K
Are absorbed primarily from the digestive tract
along with lipids of micelles
Normally diffuse into plasma membranes and lipids
in liver and adipose tissue
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Nutrition
Vitamin A A structural component of visual pigment retinal
Vitamin D Is converted to calcitriol, which increases rate of
intestinal calcium and phosphorus absorption
Vitamin E Stabilizes intracellular membranes
Vitamin K Helps synthesize several proteins, including three
clotting factors
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Nutrition
Vitamin Reserves
The body contains significant reserves of fat-
soluble vitamins
Normal metabolism can continue several
months without dietary sources
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Metabolic Rate
Calories Energy required to raise 1 g of water 1 degree Celsius
is a calorie (cal)
Energy required to raise 1 kilogram
of water 1 degree Celsius is a Calorie (Cal)=
kilocalorie (kcal)
The Energy Content of Food Lipids release 9.46 Cal/g
Carbohydrates release 4.18 Cal/g
Proteins release 4.32 Cal/g
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Metabolic Rate
Basal Metabolic Rate (BMR)
Is the minimum resting energy expenditure
Of an awake and alert person
Measured under standardized testing conditions
Measuring BMR
Involves monitoring respiratory activity
Energy utilization is proportional to oxygen
consumption
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Metabolic Rate
Hormonal Effects
Thyroxine controls overall metabolism
T4 assay measures thyroxine in blood
Cholecystokinin (CCK) and adrenocorticotropic
hormone (ACTH) suppress appetite
Leptin is released by adipose tissues during
absorptive state and binds to CNS neurons that
suppress appetite