Transcript Slide 1

Metabolism:
Transformations and
Interactions
Chapter 7
Introduction
 Energy
 Heat for temperature maintenance
 Mechanical to move muscles
 Electrical for nerve impulses
 Chemical- how energy is stored
in food and body (ATP)
 Metabolism
 Release of energy, water, and carbon
dioxide
Chemical Reactions in the Body
 Energy metabolism after absorption
 How body obtains & uses energy from food
 Where does a lot of metabolism happen?
 In Cells, liver cells especially
 Anabolism – condensation rxn’s
 Requires energy to build body’s compounds
 Catabolism – hydrolysis rxn’s
 Releases energy when compounds are
broken down
A Typical Cell
Inside the cell membrane lies the
cytoplasm, a lattice-type structure
that supports and controls the
movement of the cell’s structures.
A protein-rich jelly-like fluid called
cytosol fills the spaces within the
lattice. The cytosol contains the
enzymes involved in glycolysis.a
This network of
membranes is known as
smooth endoplasmic
reticulum—the
site of lipid synthesis.
A membrane encloses each cell’s
contents and regulates the passage
of molecules in and out of the cell.
A separate inner membrane
encloses the cell’s nucleus.
Inside the nucleus are
The chromosomes,
Which contain the
genetic material DNA.
Known as the
“powerhouses” of the
cells, the mitochondria
are intricately folded
membranes that house
all the enzymes
involved in the
conversion of pyruvate
to acetyl CoA, fatty
acid oxidation, the TCA
cycle, and the electron
transport chain.
Rough endoplasmic reticulum
is dotted with ribosomes—the
site of protein synthesis.
Chemical Reactions in the Body
ANABOLIC REACTIONS
Glycogen
Triglycerides
Uses
energy
Uses
energy
+
Glucose
Glucose
Protein
Uses
energy
Glycerol
+
Fatty acids
Amino acids + Amino acids
Anabolic reactions include the making of glycogen, triglycerides, and protein; these reactions require
differing amounts of energy.
CATABOLIC REACTIONS
Glycogen
Glucose
Yields
energy
Triglycerides
Glycerol
Yields
energy
Protein
Fatty acids
Yields
energy
Amino acids
Yields
energy
Catabolic reactions include the breakdown of glycogen, triglycerides, and protein; the further
catabolism of glucose, glycerol, fatty acids, and amino acids releases differing amounts of energy.
Much of the energy released is captured in the bonds of adenosine triphosphate (ATP).
Metabolism in the Body
 Transfer of energy in reactions – ATP
 Released during breakdown of glucose, fatty
acids, and amino acids
 Form of phosphate groups
 Negative charge – vulnerable to hydrolysis
 Provides energy for all cell activities
 Coupled reactions
 Efficiency
 Heat loss
Adenosine Triphosphate (ATP)
+
Adenosine
3 phosphate groups
Capture/Release of Energy by ATP
ATP
1
ADP
1
ATP
ADP + P
2
Energy is released when a high-energy
phosphate bond in ATP is broken. Just as a
battery can be used to provide energy for a
variety of uses, the energy from ATP can be used
to do most of the body’s work—contract muscles,
transport compounds, make new molecules, and
more. With the loss of a phosphate group,
high-energy ATP (charged battery) becomes
low-energy ADP (used battery).
2 Energy is required when a phosphate group is
attached to ADP, making ATP. Just as a used
battery needs energy from an electrical outlet to
get recharged, ADP (used battery) needs energy
from the breakdown of carbohydrate, fat, and
protein to make ATP (recharged battery).
Helpers in Metabolic Rxn’s
 Enzymes
 Facilitators of metabolic reactions
 Coenzymes
 Organic
 Associate with enzymes
 Without coenzyme, an enzyme cannot
function
II. Break Down Nutri. for Energy
 Digestion
 Carbohydrates into glucose & other
monosaccharides
 Fats (triglycerides) into glycerol and fatty acids
 Proteins into amino acids
 Digestion Products: molecules of glucose,
glycerol, amino acids, and fatty acids
 Catabolism
 Carbon, nitrogen, oxygen, hydrogen
Nutrient Breakdown for Energy
 Two energy-releasing compounds headed
for TCA cycle and electron transport chain
 Pyruvate
 3-carbon structure
 Can be used to make glucose
 Acetyl CoA
 2-carbon structure
 Cannot be used to make glucose
Acetate
(coenzyme A missing)
Pyruvate
Breaking Down Nutrients
for Energy
Protein
Carbohydrate
Amino
acids
Glucose
Fat
Glycerol
Fatty
acids
Pyruvate
1
1 All of the energy-yielding nutrients—
protein, carbohydrate, and fat—can
be broken down to acetyl CoA.
Acetyl
CoA
2
2 Acetyl CoA can enter the
TCA cycle.
TCA cycle
3
Electron
transport chain
44
ATP
3 Most of the reactions above release
hydrogen atoms with their electrons,
which are carried by coenzymes to
the electron transport chain.
4 ATP is synthesized.
55
Water
5 Hydrogen atoms react with oxygen
to produce water.
Glucose has 6 carbons
Glycerol has 3 carbons
Amino acids have varying no.’s of carbons
Breaking Down Nutrients for
Energy – Glucose
 Glucose to pyruvate
 Glycolysis
 For short energy bursts and TCA cycle prep
 1 glucose yields 2 pyruvate
 Hydrogen atoms carried to electron transport
chain
 Pyruvate can be converted back to glucose
 Liver cells and kidneys (to some extent)
Glucose to Pyruvate
Glycolysis
 Fructose and galactose enter
same pathway glucose is on
 Needs ATP for jump start
 file:///E:/Media/Animations/chapter7/0
705.html
Glycolysis
A little ATP is used to start glycolysis.
Glucose
Galactose and fructose enter glycolysis at
different places, but all continue on the
same pathway.
Uses energy
(ATP)
In a series of reactions, the 6-carbon
glucose is converted
to other 6-carbon compounds, which
eventually split into
two interchangeable 3-carbon
compounds.
Uses energy
(ATP)
A little ATP is produced,
and coenzymes carry the hydrogens
and their electrons to the electron
transport chain.
These 3-carbon compounds go through a
series of conversions, producing another
3-carbon compound, each slightly
different.
Eventually, the 3-carbon compounds are
converted to pyruvate. Glycolysis of one
molecule of glucose produces two
molecules of pyruvate.
Coenzyme
Coenzyme
Coenzym
e
Coenzy
me
To Electron
Transport Chain
Yields
energy (ATP)
Yields
energy 2 Pyruvate
(ATP)
NOTE: These arrows point down
indicating the breakdown of
glucose to pyruvate during energy
metabolism. (Alternatively, the
arrows could point up indicating
the making of glucose from
pyruvate, but that is not the focus
of this discussion.)
Breaking Down Glucose for Energy
 Pyruvate’s options
 Quick energy needs – anaerobic
Pyruvate-to-lactate or back to
glucose
 Slower energy needs – aerobic
Pyruvate-to-acetyl CoA
(irreversible to glucose)
Breaking Down Glucose for
Anaerobic Energy
 Pyruvate conversion to lactate
 Pyruvate accepts hydrogens
 Occurs during high-intensity exercise, has
limited minutes
 Produces ATP quickly when too few
mitochondria or low oxygen
 Accumulation of lactate in muscles from
rapid glycolysis
 Liver’s Cori cycle- lactate back to glucose
Breaking Down Glucose for
Anaerobic Energy
In the liver:
In the muscle:
Glucose returns
to the muscles
Glucose
Glucose
Coenzyme
Coenzyme
Yields energy
(ATP)
Uses energy
(ATP)
Coenzyme
Coenzyme
Coenzyme
Coenzyme
Lactate travels
to the liver
2 Pyruvate
2 Lactate
Working muscles break down most of their glucose molecules
anaerobically to pyruvate. If the cells lack sufficient mitochondria
or in the absence of sufficient oxygen, pyruvate can accept the
hydrogens from glucose breakdown and become lactate. This
conversion frees the coenzymes so that glycolysis can continue.
NOTE: Other figures in this chapter focus narrowly on the carbons of
pyruvate. Its oxygen group is included in this figure to more clearly
illustrate this reaction. See definitions for the chemical structures of
pyruvate and lactate.
2 Lactate
Liver enzymes can convert
lactate to glucose, but this
reaction requires energy. The
process of converting lactate
from the muscles to glucose
in the liver that can be
returned to the muscles is
known as the Cori cycle.
In the liver:
Cori Cycle
Glucose
Uses
energy
(ATP)
2 Lactate
Stepped Art
Breaking Down Glucose
for AEROBIC Energy
 Pyruvate-to-Acetyl CoA
 Pyruvate enters mitochondria of cell
Carbon removed – becomes carbon
dioxide
2-carbon compound joins with CoA
becoming acetyl CoA – irreversible
Breaking Down Glucose
for AEROBIC Energy
2 Pyruvate Coenzyme
Coenzyme
2 CoA
Coenzyme
Coenzyme
To Electron
Transport
Chain
2 Carbon
dioxide
CoA
CoA
2 Acetyl CoA
To TCA Cycle
Each pyruvate loses a carbon as carbon dioxide
and picks up a molecule of CoA, becoming
acetyl CoA. The arrow goes only one way
(down) because the step is not reversible.
Breaking Down Glucose for
AEROBIC Energy… now or later
 Acetyl CoA’s options – 2 functions
1. Synthesize fats when ATP is abundant
 Any molecule that can make acetyl CoA can
make fat (glucose, glycerol, fatty/amino acids)
 Acetyl CoA itself can only make fatty acids
2. Generate more ATP through TCA cycle than
glycolysis
 Hydrogens – electron transport chain
Paths of Pyruvate and Acetyl CoA
Glucose
Glycerol
Amino acids
(glucogenic)
Pyruvate
Lactate
Amino acids
(ketogenic)
Acetyl CoA
Fatty acids
NOTE: Amino acids that can be used to make glucose are called glucogenic;
amino acids that are converted to acetyl CoA are called ketogenic.
Summary of Glucose to Acetyl CoA
Glucose
Coenzyme
Coenzyme
Coenzyme
Coenzyme
To Electron
Transport
Chain
2 Pyruvate
Coenzyme
Coenzyme
2 CoA
Coenzyme
Coenzyme
To Electron
Transport
Chain
2 Carbon
dioxide
CoA
CoA
2 Acetyl CoA
To TCA Cycle
IN SUMMARY
1 glucose yields 2 pyruvate,
which yield 2 acetyl CoA.
Breaking Down Glycerol and
Fatty Acids from TG for Energy
 Glycerol into pyruvate
 Glycerol can be converted to
 Glucose
 Pyruvate
 Fatty acids into Acetyl CoA
 Fatty acid oxidation
 2-carbon units at a time join with CoA
 Hydrogens and electrons carried to electron
transport chain
Glycerol
Pyruvate
Breaking Down Glycerol and
Fatty Acids from TG for Energy
 Fatty Acid to Acetyl CoA
 2 fatty acids are snapped off at a time to
combine with CoA to make Acetyl CoA
(oxidation rxn)
 file:///E:/Media/Animations/chapter7/0710.ht
ml
 16-carbon fatty acid yields 8 Acetyl CoA
Breaking Down Glycerol
and Fatty Acids for Energy
Fatty Acid to Acetyl CoA
Breaking Down Glycerol
and Fatty Acids for Energy
Breaking Down Glycerol
and Fatty Acids for Energy
Glycerol
Fatty acids
18 C
18 C
18 C
3C
54 C
A typical triglyceride contains only one small molecule of glycerol (3 C) but
has three fatty acids (each commonly 16 C or 18 C, or about 48 C to 54 C in
total). Only the glycerol portion of a triglyceride can yield glucose.
Fats Enter the Energy Pathway
Glucose
Fat (triglycerides)
Glycerol
Pyruvate
Fatty acids
CoA
CoA
Carbon
dioxide
CoA
Acetyl CoA
Coenzyme
Coenzyme
To
Electron
Transport
Chain
To TCA
Cycle
Glycerol enters the glycolysis pathway about midway between glucose and pyruvate and
can be converted to either. Fatty acids are broken down into 2-carbon fragments that
combine with CoA to form acetyl CoA (shown in Figure 7-11).
IN SUMMARY A 16-carbon fatty acid yields 8 acetyl CoA.
Fats Enter the Energy Pathway
• Product of 16-C fatty acid is 8 Acetyl CoA
for now or later
file:///E:/Media/Animations/chapter7/0711.html
Breaking Down Amino Acids
for Energy

 Amino acids into glucose, then energy
 Several entry points in energy pathway
 Converted to pyruvate (glucogenic)
 Converted to acetyl CoA (ketogenic)
 Enter TCA cycle directly (glucogenic)
 Amino acids-to-glucose
Breaking Down Amino Acids
for Energy
Deamination of amino acids (lose amino N-group)
Breaking Down Amino Acids
for Energy
Amino acids
Most amino acids
can be used to
synthesize glucose;
they are glucogenic.
Pyruvate
CoA
Coenzyme
Coenzyme
Some amino acids
are converted
directly to acetyl
CoA; they are
ketogenic.
Some amino acids
can enter the TCA
cycle directly;
they are glucogenic.
Carbon
dioxide
To
electron
transport
chain
CoA
Acetyl CoA
To TCA Cycle
NOTE: Deamination and the synthesis of urea are discussed and illustrated in Chapter 6.
The arrows from pyruvate and the TCA cycle to amino acids are possible only for
nonessential amino acids; remember, the body
cannot make essential amino acids.
The TCA Cycle
 Products of glucose, fat and amino acids
now enter the TCA Cycle
 Where? Inner compartment of mitochondria
 Circular path because OAA is regenerated
 Oxaloacetate – made primarily from pyruvate
 Acetyl CoA goes one direction
 Carbon dioxide, H with electrons released
 Coenzymes from niacin and riboflavin
transfer H and electrons to Electron
Transport Chain (ETC)
TCA Cycle
 OAA starts the cycle
 C released as CO2; CoA releases
H and electrons
 Each cycle releases 8 electrons total
 file:///E:/Media/Animations/chapter7/0718.html
Acetyl CoA
Pyruvate
(from carbon
dioxide)
(as carbon
dioxide)
Oxaloacetate
Coenzyme
Coenzyme
CoA
NOTE: Knowing that
glucose produces
pyruvate during
glycolysis and that
oxaloacetate must be
available to start the TCA
cycle, you can
understand why the
complete oxidation of fat
requires carbohydrate.
Coenzyme
Coenzyme
Coenzyme
(as carbon
dioxide)
Coenzyme
Coenzyme
Coenzyme
To Electron
Transport Chain
Yields energy (captured in highenergy compound similar to ATP)
To Electron
(as carbon dioxide) Transport Chain
Electron Transport Chain
 Energy captured in ATP bonds
 The physical chain mounted on inner
membrane of mitochondria (sl. 56)
 Series of proteins acting as electron “carriers”
 Electrons passed from carrier to carrier
 End of chain –Oxygen accepts electrons, adds
H to form water, water released
 Rush of H ions into inner mitochondrion powers
ATP synthesis
Outer compartment
Outer membrane
(site of fatty
acid activation)
Cytosol
(site of
glycolysis)
A typical cell
A mitochondrion
Site of the Electron Transport Chain
Inner membrane
(site of electron
transport chain)
Inner compartment
(site of pyruvate-to-acetyl
CoA, fatty acid oxidation,
and TCA cycle)
file:///E:/Media/Animations/chapter7/0
719.html
Central Pathways of Energy Metabolism
Energy Balance – Feasting
 Too much food? Metabolism favors fat
formation
 Regardless of excess from protein, fat, or
carbohydrates
 Dietary fat to body fat is most direct and
efficient conversion
 Carbohydrate and protein have other roles to
fulfill before conversion to body fat
 Fuel mix is ideal (balance)
Lots of mini Hydrogen Bombs vs Fewer
Fatty acid
Glucose
Fat provides more energy because the bonds in fat
molecules are easily oxidized and result in more ATP
Feasting Reserves for Fasting
 Glucose, glycerol, and fatty acids are used, then
excess stored. Fasting state draws on these
stores.
 Glucose needed for Central Nervous Sys.
 Glycogen and fat glycerol are released
 Some amino acids can go to pyruvate
 Ketones produced when no glucose
 Basal metabolism slowed by hormones
 Starvation: muscle wasting, organ slowdown
and failure, impaired immunity and vision
Feasting to Fasting to Starvation
Feasting
A When a person overeats (feasting): When a person eats in excess of energy needs, the body stores a
small amount of glycogen and much larger quantities of fat.
Food component:a
Carbohydrate
Fat
Is broken down in the body to:
Glucose
Fatty acids
And then used for:
Liver and muscle
glycogen stores
Body fat stores
Loss of nitrogen
in urine (urea)
Protein
aAlcohol
Amino acids
Body proteins
is not included because it is a toxin and not a nutrient, but it does contribute energy to
the body. After detoxifying the alcohol, the body uses the remaining two carbon
fragments to build fatty acids and stores them as fat.
2-3 hours after eating
B When a person draws on stores (fasting): When nutrients from a meal are no longer available to provide
energy (about 2 to 3 hours after a meal), the body draws on its glycogen and fat stores for energy.
Storage component:
Is broken down in the body to:
And then used for:
Liver and muscle
Glycogen
storesb
Glucose
Fatty acids
Body fat
stores
bThe
Energy for the
brain, nervous
system, and
red blood cells
Energy for
other cells
muscles’ stored glycogen provides glucose only for the muscle in which the glycogen is stored.
Fasting
Body component:
Body
protein
Is broken down in the body to:
Loss of nitrogen in urine (urea)
N
Amino acids
Glucose
Ketone
bodies
And then used for :
Energy for the
brain, nervous
system, and
red blood cells
Energy for
other cells
Body fat
Fatty acids
C If the fast continues beyond glycogen depletion: As glycogen stores dwindle (after about 24 hours of
starvation), the body begins to break down its protein (muscle and lean tissue) to amino acids to
synthesize glucose needed for brain and nervous system energy. In addition, the liver converts fats to
ketone bodies, which serve as an alternative energy source for the brain, thus slowing the breakdown of
body protein.
Early Fasting Stage: 2-3 hrs
 Carbohydrate, fat, and protein are all
eventually used for energy
 Begin with release of glucose from glycogen
and fatty acids from adipose
 Low blood glucose levels signal
 Fat breakdown
 Release of amino acids from muscles
Continued Fasting
 Protein meets glucose needs via breakdown of
body proteins (amino acids yielding pyruvate)
for
 Nervous system
 Red blood cells
 Shift to ketosis
 Acetyl CoA makes ketone bodies to fuel brain
 Slows the rate of body protein breakdown
 Keto acid production rises, lowering body pH
 Acidic blood denatures proteins
Ketone Bodies
1 1) The first step in the
formation of ketone bodies is
the condensation of two
molecules of acetyl CoA and
the removal of the CoA to
form a compound that is
converted to the first ketone
body.
Acetyl CoA
Acetyl CoA
A ketone, acetoacetate
2 2) This ketone body may lose a
molecule of carbon dioxide to
become another ketone.
3 3) Or, the acetoacetate may add two
hydrogens, becoming another
ketone body (beta-hydroxybutyrate).
See Appendix C for more details.
A ketone, acetone
Ketosis/ Very low-carb diets
 Ketosis causes a loss of appetite
 Slowing of metabolism
 Hormones
 Reduces energy output
 Supports weight loss but not fat loss
 Symptoms of starvation
 Physical symptoms
 Psychological symptoms
Low-Carbohydrate Diets
 Metabolism similar to fasting
 Uses glycogen and protein stores, body
fluids + minerals first
 Gluconeogenesis when glycogen is depleted
 Body tissues used somewhat even when
protein provided in diet
 Ketogenic diet fat losses more quickly
regained
Highlight 7
Alcohol and Nutrition
Alcohol in Beverages
 Potential health
benefits
 Alcohols
 Glycerol
 Ethanol
 Lipid solvents
 Moderation
 Definition of “drink”
Alcohol in the Body
 Alcohol’s special privileges
 No digestion
 Quick absorption
 Slowing absorption
 Stomach
 Alcohol dehydrogenase
 Small intestine
 Priority over nutrients
Alcohol Arrives in the Liver
 Liver cells
 First to receive alcohol-laden blood




Alcohol dehydrogenase
Disrupts liver activity
Can permanently change liver cell structure
Rate of alcohol metabolism
 Acetaldehyde
 Acetate
Alcohol Arrives in the Liver
Alcohol Disrupts the Liver
 Nicotinamide adenine dinucleotide (NAD)
 Glycolysis
 TCA cycle
 Electron transport chain




Development of fatty liver
Damage to central nervous system
Inflammation of joints
Amino acid and protein metabolism
Alcohol Arrives in the Liver
Alcohol Arrives in the Liver
 Immune system functioning
 Alcohol interferes with drug metabolism
 Microsomal ethanol-oxidizing system
(MEOS)
Alcohol Arrives in the Brain
 Sedates inhibitory nerves
 Acts as central nervous system depressant
 Blood alcohol levels and brain responses
 Death of liver and brain cells
 Depression of antidiuretic hormone (ADH)
 Loss of body water
 Loss of important minerals
Alcohol Arrives in the Brain
1 Judgment and reasoning centers are most
1 Frontal
lobe
sensitive to alcohol. When alcohol flows to
the brain, it first sedates the frontal lobe,
the center of all conscious activity. As the
alcohol molecules diffuse into the cells of
these lobes, they interfere with reasoning
and judgment.
2 Speech and vision centers in the midbrain
are affected next. If the drinker drinks faster
than the rate at which the liver can oxidize
the alcohol, blood alcohol concentrations
rise: the speech and vision centers of the
brain become sedated.
3 Voluntary muscular control is then affected.
2 Midbrain
4 Pons, Medulla
oblongata
3 Cerebellum
At still higher concentrations, the cells in
the cerebellum responsible for coordination
of voluntary muscles are affected, including
those used in speech, eye-hand
coordination, and limb movements. At this
point people under the influence stagger or
weave when they try to walk, or they may
slur their speech.
4 Respiration and heart action are the last to
be affected. Finally, the conscious brain is
completely subdued, and the person passes
out. Now the person can drink no more; this
is fortunate because higher doses would
anesthetize the deepest brain centers that
control breathing and heartbeat, causing
Fig. H7-4, p. 234
death.
Alcohol Arrives in the Brain
Alcohol and Malnutrition
 Can contribute to body fat and weight gain
 1 ounce of alcohol represents 0.5 ounce of
fat
 Central obesity
 Substituted energy
 7 kcalories per gram
 Nutrient displacement
 B vitamins
Alcohol’s Effects
 Short-term effects
 Excessive drinking
 Heavy drinking
 Binge drinking
 Long-term effects
 Third leading preventable cause of death in
U.S.
 Sobering up