If you could peer into the crystal ball and see how you were going to die, would you do anything different?

1
If you could peer into the crystal ball and see
how you were going to die, would you do anything
different?
2
Lecture 6 Diabetes, sugar, and ATP

• Objectives
• Understand how sugar metabolism works
• Understand how to make ATP
• Understand where sugar comes from
• Understand how sugar metabolism affects you

• Key Terms
• metabolism, gradient, equilibrium,
  phosphorylation, ATP, ADP
• electron transport, glycolysis, insulin,
  glycogen, glucagon
• NEXT WEEK
• Cell Division and Cancer

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Leading Causes of Deaths

• Heart Disease 700,142
• Cancer 553,768
• Stroke 163,538
• Lung diseases 123,013
• Accidents (unintentional injuries) 101,537
• Diabetes 71,372
• Influenza/ Pneumonia 62,034
• Alzheimer's disease 53,852
• Kidney Disease 39,480
• Septicemia (infection) 32,238

(Most current data available are for U.S. in
2001) www.cdc.gov/nchs/fastats/lcod.htm
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I dont have to worry about that stuff till I get
old!
Relative to the national population of 20-24s,
are MSU students less likely to die from the top
3?

• All races, both sexes, 2024 years
• Accidents (unintentional injuries)
• Assault (homicide)
• Intentional self-harm (suicide)
• Cancer
• Heart disease
• Genetic abnormalities
• Human immunodeficiency virus (HIV)
• Stroke
• Influenza and pneumonia
• Diabetes

Its difficult for one to prevent bad luck, or
being a victim?
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Two Types of Diabetes

• Type 1
• Juvenile diabetes
• Autoimmune disease
• Beta cells in pancreas are killed by defense
  responses
• Treated with insulin injections

• Type 2
• Adults affected
• Insulin sensing system impaired.
• Beta cells stop making insulin.
• Pancreas burns out
• Treated with diet, drugs

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Diabetes Mellitis

• Cells in muscles, liver and fat dont use insulin
  properly
• Disease in which excess glucose accumulates in
  blood, then urine
• Signs and Symptoms
• Excessive urination
• Constant thirst and or hunger
• Fatigue
• Weight loss
• Blurred vision
• Sores that dont heal

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Risk Factors

• Age
• Overweight
• Inactive (exercise gt 3x/week)
• Family history African, American Indian, Asian,
  Pacific Islander, Hispanic or Latino descent.
• Siblings or parents have diabetes
• Gestational diabetes
• Blood pressure over 140/90
• HDL (good) cholesterol is low and triglicerides
  are high

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Reducing Risks

• Physical activity- 30 min 5 days/week
• Diet Modification
• Low fat- 25 of calories max
• Low alcohol
• Maintain Reasonable body mass
• No crash diets
• Modify dietary intake

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What, me worry?

• Myths
• When I leave MSU and get a job I will have as
  much or more free time than I do now. (Ill still
  exercise as much as I do now.
• Im naturally healthy, I dont have to worry.
• I dont have any risk factors so Im immune!

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Diabetes Prevention Program

• Program Risk
  Reduction
• Healthy diet and exercise 58
• Healthy diet and exercise (old folks) 71
• Prevention drug 31
• Control group (no change)
• Participants were overweight, with high blood
  sugar (Pre-Diabetes, impaired tolerance)

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Question 1

• Energy for metabolic processes only comes from
  Sugar
• A. True
• B. False

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Quick Anatomy Review
IN
MOUTH(ORAL CAVITY)
PHARYNX
ESOPHAGUS
STOMACH
LIVER
GALLBLADDER
SMALL INTESTINE
PANCREAS
LARGE INTESTINE (COLON)
RECTUM
OUT
ANUS
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Absorption Mechanisms

• Food is broken down to macro molecules
• Macro molecules are disassembled by enzymes in
  the intestines
• Actively transported across membrane
• Monosaccharides
• Amino acids
• Nutrients diffuse from gut cells into blood stream

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bile salts
bile salts
FAT GLOBULES
MICELLES
carbohydrates
EMULSIFICATION DROPLETS
proteins
EPITHELIAL CELL
CHYLOMICRONS
INTERNAL ENVIRONMENT
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Control of Glucose Metabolism
insulin
Glucose is absorbed
Glucose uptake
Glucose to glycogen
Glucose falls
Cells use glucose
Glucose rises
Glycogen to glucose
glucagon
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Many cells, especially muscle cells, take up
glucose and use it as an energy source or
convert it to glycogen.
INSULIN
Beta cells of pancreas release insulin into blood.
Liver converts glucose to glycogen, fats,
proteins.
Blood glucose levels decline to a set point
stimulus calling for insulin diminishes.
Stimulus Glucose is absorbed following a meal.
Stimulus Cells use or store glucose between
meals.
Blood glucose levels increase to a set point
stimulus calling for glucagon diminishes.
Liver converts glycogen to glucose, stops
synthesizing glycogen.
Alpha cells of pancreas release glucagon into
blood.
GLUCAGON
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IF YOU ARE LOSTCLOSE YOUR EYESTILL UNTIL
AFTERTHE NEXT SLIDE
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Insulin
Glucose
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Click to view animation.
animation
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Using GlucoseSkeletal Muscle Structure

• A muscle is made up of muscle cells
• A muscle fiber is a single muscle cell
• Each fiber contains many myofibrils

myofibril
Dont Write This Down
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Myofibril
A myofibril is made up of thick and thin
filaments arranged in sarcomeres
Dont Write This Down
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Sarcomere

• A bundle of two types of microfilaments

ThinFilaments
ThickFilaments
Dont Write This Down
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Muscle Microfilaments

• Thin filaments
• Like two strands of pearls twisted together
• Pearls are actin
• Other proteins in grooves in filament

• Thick filaments
• Composed of myosin
• Each myosin molecule has tail and a double head

Dont Write This Down
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Sliding-Filament Model

• Sarcomere shortens because the actin filaments
  are pulled inward, toward the sarcomere center

Dont Write This Down
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Sliding-Filament Model

• Myosin heads attach to actin filaments
• Myosin heads tilt toward and pull on the actin.

• Key Concept
• Each head requires one ATP for each pull!
• There a lot of myosinheads in a muscle
• Muscle contraction requires enormous quantities
  of ATP!

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Key ConceptContraction Requires Energy

• Muscle cells require huge amounts of ATP energy
  to power contraction
• The cells have only a very small store of ATP
• There are three pathways muscle cells use to get
  ATP

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Question 2

• Cells burn insulin to make ATP
• A. True
• B. False

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ATP for Contraction
ADP Pi
Pathway 1 DEPHOSPHORYLATION CREATINE PHOSPHATE
Relaxation
Contraction
creatine
Pathway 2 AEROBIC RESPIRATION
Pathway 3 GLYCOLYSIS ALONE
glucose from bloodstream and from glycogen
breakdown in cells
oxygen
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What is ATP?
?
DEPHOSPHORYLATION! RESPIRATION! GLYCOLYSIS! Whats
ATP! AND How did we get here and where are we
going
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ATP Is Universal Energy Source

• Photosynthesizers get energy from the sun
• Animals get energy second- or third-hand from
  plants or other organisms
• Regardless, the energy is converted to the
  chemical bond energy of ATP

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Making ATP

• Plants make ATP during photosynthesis
• Cells of all organisms make ATP by breaking down
  carbohydrates, fats, and protein

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Two Main Pathways for making ATP

• Aerobic pathways
• SLOW
• Require oxygen
• Start with glycolysis in cytoplasm
• Completed in mitochondria
• (Note special membrane and gradient)

• Anaerobic pathways
• FAST
• Dont require oxygen
• Start with glycolysis in cytoplasm
• Completed in cytoplasm

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Overview of Aerobic Respiration
CYTOPLASM
glucose
ATP
GLYCOLYSIS
energy input to start reactions
(2 ATP net)
e- H
2 pyruvate
2 NADH
MITOCHONDRION
e- H
2 CO2
2 NADH
e- H
4 CO2
8 NADH
KREBS CYCLE
e- H
2
ATP
2 FADH2
e-
ELECTRON TRANSPORT PHOSPHORYLATION
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ATP
H
water
e- oxygen
TYPICAL ENERGY YIELD 36 ATP
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Main Pathways Start with Glycolysis

• Glycolysis occurs in cytoplasm
• Reactions are catalyzed by enzymes
• Glucose 2 Pyruvate
• (six carbons) (three carbons)

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Overview of Aerobic Respiration

• C6H1206 6O2 6CO2 6H20
• glucose oxygen
  carbon water
• dioxide

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Overview of Aerobic Respiration
CYTOPLASM
glucose
ATP
GLYCOLYSIS
energy input to start reactions
(2 ATP net)
e- H
2 pyruvate
2 NADH
MITOCHONDRION
e- H
2 CO2
2 NADH
e- H
4 CO2
8 NADH
KREBS CYCLE
e- H
2
ATP
2 FADH2
e-
ELECTRON TRANSPORT PHOSPHORYLATION
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ATP
H
water
e- oxygen
TYPICAL ENERGY YIELD 36 ATP
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Whats the deal with Oxygen?(electron transport
chain over simplified)

• How it Works
• Pull a hydrogen off a water (HOH to OH-)
• Pull the hydrogen (H) across a membrane
  (electrochemical GRADIENT)
• Make the H do work on its way back to OH-

• Difficult to explain without using lots of really
  cool chemistry
• Key concept If you pull water apart, it really
  wants to get back together again
• By giving the Oxygen atom in water an electron,
  it will give you a proton, which is actually a H
• Oxygen is the final electron acceptor?

http//www.sp.uconn.edu/terry/images/anim/ETS.htm
l
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Question 3

• More ATP is produced by the electron transport
  system than is produced by glycolysis
• A True
• B False

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Coenzyme Production

• Glycolysis 2 NADH
• Preparatory
• reactions 2 NADH
• Krebs cycle 2 FADH2
• . 6 NADH
• Total 2 FADH
• . 10 NADH

• Key Concepts Coenzyme production
• Krebs cycle produces activated coenzymes
• Coenzymes push electron transport

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Electron Transport Phosphorylation

• Occurs in the mitochondria
• Coenzymes deliver electrons to electron transport
  systems
• Electron transport sets up H ion gradients
• Flow of H down gradients powers ATP formation

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Electron Transport

• Electron transport systems are embedded in inner
  mitochondrial compartment
• NADH and FADH2 give up electrons that they picked
  up in earlier stages to electron transport system
• Electrons are transported through the system
• The final electron acceptor is oxygen

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Creating an H Gradient
OUTER COMPARTMENT
NADH
INNER COMPARTMENT
43
Making ATP Chemiosmotic Model
ATP
INNER COMPARTMENT
ADPPi
44
ATP Synthase in Action
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Importance of Oxygen

• Electron transport phosphorylation requires the
  presence of oxygen
• Oxygen withdraws spent electrons from the
  electron transport system, then combines with H
  to form water

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Key Points In Summary

• Glucose eventually gets broken down to carbon
  dioxide gas
• Two ways to make ATP
• Fast way - Anerobic
• No oxygen required
• Glucose isnt converted to CO2 but lactic acid
• Only net 2 ATPs/glucose
• Slow way - Aerobic
• Requires oxygen
• Glucose converted to CO2
• Net 36 ATPs/glucose

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Summary of Energy Harvest(per molecule of
glucose)

• Glycolysis
• 2 ATP formed by substrate-level phosphorylation
• Krebs cycle and preparatory reactions
• 2 ATP formed by substrate-level phosphorylation
• Electron transport phosphorylation
• 32 ATP formed

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Energy Harvest from Coenzyme Reductions

• What are the sources of electrons used to
  generate the 32 ATP in the final stage?
• 4 ATP - generated using electrons released during
  glycolysis and carried by NADH
• 28 ATP - generated using electrons formed during
  second-stage reactions and carried by NADH and
  FADH2

49
Energy Harvest Varies

• NADH formed in cytoplasm cannot enter
  mitochondrion
• It delivers electrons to mitochondrial membrane
• Membrane proteins shuttle electrons to NAD or
  FAD inside mitochondrion
• Electrons given to FAD yield less ATP than those
  given to NAD

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Energy Harvest Varies

• Liver, kidney, heart cells
• Electrons from first-stage reactions are
  delivered to NAD in mitochondria
• Total energy harvest is 38 ATP
• Skeletal muscle and brain cells
• Electrons from first-stage reactions are
  delivered to FAD in mitochondria
• Total energy harvest is 36 ATP

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Efficiency of Aerobic Respiration

• 686 kcal of energy are released
• 7.5 kcal are conserved in each ATP
• When 36 ATP form, 270 kcal (36 X 7.5) are
  captured in ATP
• Efficiency is 270 / 686 X 100 39 percent
• Key Concept Most energy is lost as heat

52
Anaerobic Pathways

• Do not use oxygen
• Produce less ATP than aerobic pathways
• Two types
• Fermentation pathways
• The burn
• The Buzz
• Anaerobic electron transport

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Fermentation Pathways

• Begin with glycolysis
• Do not break glucose down completely to carbon
  dioxide and water
• Yield only the 2 ATP from glycolysis
• Steps that follow glycolysis serve only to
  regenerate NAD

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Lactate Fermentation
GLYCOLYSIS
C6H12O6
ATP
2
energy input
2 NAD
2 ADP
NADH
2
ATP
4
2 pyruvate
energy output
2 ATP net
LACTATE FORMATION
electrons, hydrogen from NADH
2 lactate
55
Yeasts

• Single-celled fungi
• Carry out alcoholic fermentation
• Saccharomyces cerevisiae
• Bakers yeast
• Carbon dioxide makes bread dough rise
• Saccharomyces ellipsoideus
• Used to make beer and wine
• MSU hard cider project Sacchromyces banyan DV10

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Alcoholic Fermentation
GLYCOLYSIS
C6H12O6
ATP
2
2 NAD
energy input
2 ADP
NADH
2
ATP
4
2 pyruvate
energy output
2 ATP net
ETHANOL FORMATION
2 H2O
2 CO2
2 acetaldehyde
Animals Cant do this!
electrons, hydrogen from NADH
2 ethanol
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Anaerobic Electron Transport

• Carried out by certain bacteria
• Electron transport system is in bacterial plasma
  membrane
• Final electron acceptor is compound from
  environment (such as nitrate), NOT oxygen
• Doesnt require Oxygen
• Cant work with Oxygen
• ATP yield is low
• Lets bacteria live where other organisms cant

58
Question 4

• Is Insulin a
• A. Carbohydrate
• B. Protein
• C. Lipid
• D. Organophosphate

59
Energy Reserves

• Glycogen is about 1 of the bodys energy
  reserve
• Proteins is 21 of energy reserve
• Fat makes up the bulk of reserves (78 )
• Note In lecture 4 we discussed polysaccharides,
  proteins and lipids.

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Energy from Macromolecules

• Carbohydrate
• Glycogen
• Protein
• Lipids (fat)

bile salts
bile salts
FAT GLOBULES
MICELLES
carbohydrates
EMULSIFICATION DROPLETS
proteins
EPITHELIAL CELL
CHYLOMICRONS
INTERNAL ENVIRONMENT
61
Carbohydrate Breakdown and Storage

• Glucose is absorbed into blood
• Pancreas releases insulin
• Insulin stimulates glucose uptake by cells
• Cells convert glucose to glucose-6-phosphate
• Phosphate, functional group, phosphorylation
• This traps glucose in cytoplasm where it can be
  used for glycolysis

62
Making Glycogen

• If glucose intake is high, ATP-making machinery
  goes into high gear
• When ATP levels rise high enough,
  glucose-6-phosphate is diverted into glycogen
  synthesis (mainly in liver and muscle)
• Glycogen is the main storage polysaccharide in
  animals

63
Using Glycogen

• When blood levels of glucose decline, pancreas
  releases glucagon
• Glucagon stimulates liver cells to convert
  glycogen back to glucose and to release it to the
  blood
• (Muscle cells do not release their stored
  glycogen. This is their stored sugar!)

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Key Concepts

• Glucose Storage
• Glucose is used to make ATP first
• When ATP store is full, glucose is stored
• Glycogen is a big branched polymer of stored
  glucose
• Glycogen isnt very soluble so it is trapped
  inside the cell where it is stored.

65
Energy from Proteins

• Proteins are broken down to amino acids and the
  amino acids are broken down
• Amino group is removed, ammonia forms, is
  converted to urea and excreted
• Carbon backbones can enter the Krebs cycle or its
  preparatory reactions
• Key Concept Proteins can be used to make ATP in
  Krebs Cycle

66
Energy from Fats (lipids)

• Most stored fats are triglycerides
• Triglycerides are broken down to glycerol and
  fatty acids
• Fatty acids are broken down and converted to two
  carbon blocks that enter the Krebs cycle (acetyl
  CoA)
• Key Concept Fatty acids are used to make ATP
• . Conversion is slow, 2Cs at a time
• Before it can even enter Krebs Cycle

67
Processes Are Linked

• Aerobic Respiration
• Reactants
• Sugar
• Oxygen
• Products
• Carbon dioxide
• Water

• Photosynthesis
• Reactants
• Carbon dioxide
• Water
• Products
• Sugar
• Oxygen

68
Machinery of Noncyclic Electron Flow
H2O
photolysis
e
e
ATP SYNTHASE
NADPH
NADP
ATP
ADP Pi
PHOTOSYSTEM I
PHOTOSYSTEM II
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ATP Formation in Plants

• When water is split during photolysis, hydrogen
  ions are released into thylakoid compartment.
  (Electrochemical GRADIENT)
• More hydrogen ions are pumped into the thylakoid
  compartment when the electron transport system
  operates

70
ATP Formation

• Electrical and H concentration gradient exists
  between thylakoid compartment and stroma
• H flows down gradients into stroma through ATP
  synthesis
• Flow of ions drives formation of ATP

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Two Important Pathways

• Light Reaction
• Makes ATP from light energy

• Dark Reaction
• Makes glucose by burning ATP
• Uses CO2 from the air and water to make glucose

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Summary of Photosynthesis
light
LIGHT-DEPENDENT REACTIONS
6O2
12H2O
ATP
NADPH
NADP
ADP Pi
PGA
CALVIN-BENSON CYCLE
PGAL
6CO2
RuBP
P
C6H12O6
(phosphorylated glucose)
end product (e.g. sucrose, starch, cellulose)
73
Question 5

• Carbon Dioxide Gas is used to build energy
  storage molecules in the liver
• A True
• B False

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Please hand your quiz sheet to Andrea or Leah on
your way outNote They will only accept one
answer form from each person
If you are interested in the first extra credit
project, please come to the front of the class
room