Metabolism: Transformations and Interactions

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Metabolism Transformations and Interactions

• Chapter 7

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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

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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 rxns
• Requires energy to build bodys compounds
• Catabolism hydrolysis rxns
• Releases energy when compounds are broken down

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A Typical Cell
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Inside the cell membrane lies the cytoplasm, a
lattice-type structure that supports and controls
the movement of the cells structures. A
protein-rich jelly-like fluid called cytosol
fills the spaces within the lattice. The cytosol
contains the enzymes involved in glycolysis.a
A separate inner membrane encloses the cells
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.
This network of membranes is known as smooth
endoplasmic reticulumthe site of lipid synthesis.
Rough endoplasmic reticulum is dotted with
ribosomesthe site of protein synthesis.
A membrane encloses each cells contents and
regulates the passage of molecules in and out of
the cell.
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Chemical Reactions in the Body
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ANABOLIC REACTIONS
Glycogen
Triglycerides
Protein

Uses energy
Uses energy
Uses energy
Glucose

Glucose
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
Triglycerides
Protein
Glucose
Glycerol
Amino acids
Fatty acids
Yields energy
Yields energy
Yields energy
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).
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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

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Adenosine Triphosphate (ATP)

Adenosine
3 phosphate groups
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Capture/Release of Energy by ATP
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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
bodys workcontract 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).
ATP ADP
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1
ATP breakdown
ATP
ADP P
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).
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ATP synthesis
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Helpers in Metabolic Rxns

• Enzymes
• Facilitators of metabolic reactions
• Coenzymes
• Organic
• Associate with enzymes
• Without coenzyme, an enzyme cannot function

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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

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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

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Acetate (coenzyme A missing)
Pyruvate
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Breaking Down Nutrients for Energy
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Protein
Fat
Carbohydrate
Fatty acids
Amino acids
Glucose
Glycerol
Pyruvate
All of the energy-yielding nutrients protein,
carbohydrate, and fatcan be broken down to
acetyl CoA.
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Acetyl CoA
Acetyl CoA can enter the TCA cycle.
TCA cycle
Most of the reactions above release hydrogen
atoms with their electrons, which are carried by
coenzymes to the electron transport chain.
Electron transport chain
ATP is synthesized.
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Hydrogen atoms react with oxygen to produce water.
Water
ATP
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Glucose has 6 carbons
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Glycerol has 3 carbons
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Amino acids have varying no.s of carbons
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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)

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Glucose to Pyruvate Glycolysis

• Fructose and galactose enter same pathway
  glucose is on
• Needs ATP for jump start
• file///E/Media/Animations/chapter7/0705.html

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Glycolysis
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Glucose
A little ATP is used to start glycolysis.

Uses energy (ATP)
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.
Coenzyme
Coenzyme
To Electron Transport Chain
A little ATP is produced, and coenzymes carry
the hydrogens and their electrons to the electron
transport chain.
Coenzyme
Coenzyme
Yields energy (ATP)
These 3-carbon compounds go through a series of
conversions, producing another 3-carbon compound,
each slightly different.
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.)
Eventually, the 3-carbon compounds are converted
to pyruvate. Glycolysis of one molecule of
glucose produces two molecules of pyruvate.
Yields energy (ATP)
2 Pyruvate
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Breaking Down Glucose for Energy

• Pyruvates options
• Quick energy needs anaerobic
• Pyruvate-to-lactate or back to glucose
• Slower energy needs aerobic
• Pyruvate-to-acetyl CoA (irreversible to glucose)

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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
• Livers Cori cycle- lactate back to glucose

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Breaking Down Glucose for Anaerobic Energy
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In the liver
In the muscle
Glucose returns to the muscles
Glucose
Glucose
Coenzyme
Coenzyme
Uses energy (ATP)
Yields energy (ATP)
Coenzyme
Coenzyme
Coenzyme
Coenzyme
Lactate travels to the liver
2 Pyruvate
2 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.
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.
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Cori Cycle
Stepped Art
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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

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Breaking Down Glucose for AEROBIC Energy
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2 Pyruvate
Coenzyme
Coenzyme
To Electron Transport Chain
Coenzyme
2 CoA
Coenzyme
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.
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Breaking Down Glucose for AEROBIC Energy now or
later

• Acetyl CoAs options 2 functions
• 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
• Generate more ATP through TCA cycle than
  glycolysis
• Hydrogens electron transport chain

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Paths of Pyruvate and Acetyl CoA
Glucose
Glycerol
Amino acids (glucogenic)
Pyruvate
Lactate
Amino acids (ketogenic)
Fatty acids
Acetyl CoA
NOTE Amino acids that can be used to make
glucose are called glucogenic amino acids that
are converted to acetyl CoA are called ketogenic.
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Summary of Glucose to Acetyl CoA
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Glucose
Coenzyme
Coenzyme
Coenzyme
To Electron Transport Chain
Coenzyme
2 Pyruvate
Coenzyme
Coenzyme
2 CoA
To Electron Transport Chain
Coenzyme
Coenzyme
2 Carbon dioxide
CoA
CoA
IN SUMMARY 1 glucose yields 2 pyruvate, which
yield 2 acetyl CoA.
2 Acetyl CoA
To TCA Cycle
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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

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Glycerol
Pyruvate
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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.html
• 16-carbon fatty acid yields 8 Acetyl CoA

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Breaking Down Glycerol and Fatty Acids for Energy
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Fatty Acid to Acetyl CoA
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Breaking Down Glycerol and Fatty Acids for Energy
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Breaking Down Glycerol and Fatty Acids for Energy
Fatty acids
Glycerol
18 C
18 C
18 C
54 C
3 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.
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Fats Enter the Energy Pathway
Glucose
Fat (triglycerides)
Glycerol
Fatty acids
Pyruvate
CoA
To Electron Transport Chain
Carbon dioxide
CoA
Coenzyme
Coenzyme
CoA
Acetyl CoA
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.
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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
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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

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Breaking Down Amino Acids for Energy
Deamination of amino acids (lose amino N-group)
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Breaking Down Amino Acids for Energy
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Amino acids
Most amino acids can be used to synthesize
glucose they are glucogenic.
Pyruvate
CoA
Coenzyme
To electron transport chain
Coenzyme
Carbon dioxide
Some amino acids are converted directly to acetyl
CoA they are ketogenic.
CoA
Acetyl CoA
Some amino acids can enter the TCA cycle
directly they are glucogenic.
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.
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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)

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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

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Acetyl CoA
Pyruvate
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.

(from carbon dioxide)
(as carbon dioxide)
CoA
Oxaloacetate
Coenzyme
Coenzyme
Coenzyme
Coenzyme
Coenzyme
(as carbon dioxide)
Coenzyme
Coenzyme
Coenzyme
To Electron Transport Chain
Yields energy (captured in high-energy compound
similar to ATP)
To Electron Transport Chain
(as carbon dioxide)
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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

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Outer compartment
Outer membrane (site of fatty acid activation)
Cytosol (site of glycolysis)
Inner membrane (site of electron transport chain)
A typical cell
A mitochondrion
Inner compartment (site of pyruvate-to-acetyl CoA,
fatty acid oxidation, and TCA cycle)
Site of the Electron Transport Chain
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file///E/Media/Animations/chapter7/0719.html
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Central Pathways of Energy Metabolism
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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)

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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
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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

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Feasting to Fasting to Starvation
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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 componenta
And then used for
Is broken down in the body to
Glucose
Liver and muscle glycogen stores
Carbohydrate
Body fat stores
Fatty acids
Fat
Loss of nitrogen in urine (urea)
Amino acids
Protein
Body proteins
aAlcohol 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.
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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.
And then used for
Is broken down in the body to
Storage component
Energy for the brain, nervous system, and red
blood cells
Liver and muscle Glycogen storesb
Glucose
Fatty acids
Body fat stores
Energy for other cells
bThe muscles stored glycogen provides glucose
only for the muscle in which the glycogen is
stored.
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Fasting
Body component
And then used for
Is broken down in the body to
Loss of nitrogen in urine (urea)
N
Body protein
Energy for the brain, nervous system, and red
blood cells
Glucose
Amino acids
Ketone bodies
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.
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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

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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

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Ketone Bodies
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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
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2) This ketone body may lose a molecule of carbon
dioxide to become another ketone.
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3) Or, the acetoacetate may add two hydrogens,
becoming another ketone body (beta-hydroxybutyrate
). See Appendix C for more details.
A ketone, acetone
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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

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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

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Highlight 7

• Alcohol and Nutrition

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Alcohol in Beverages

• Potential health benefits
• Alcohols
• Glycerol
• Ethanol
• Lipid solvents
• Moderation
• Definition of drink

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Alcohol in the Body

• Alcohols special privileges
• No digestion
• Quick absorption
• Slowing absorption
• Stomach
• Alcohol dehydrogenase
• Small intestine
• Priority over nutrients

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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

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Alcohol Arrives in the Liver
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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

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Alcohol Arrives in the Liver
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Alcohol Arrives in the Liver

• Immune system functioning
• Alcohol interferes with drug metabolism
• Microsomal ethanol-oxidizing system (MEOS)

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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

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Alcohol Arrives in the Brain
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1
Judgment and reasoning centers are most 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.
Frontal lobe
1
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. 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.
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Pons, Medulla oblongata
2
Midbrain
3
Cerebellum
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 death.
4
Fig. H7-4, p. 234
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Alcohol Arrives in the Brain
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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

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Alcohols Effects

• Short-term effects
• Excessive drinking
• Heavy drinking
• Binge drinking
• Long-term effects
• Third leading preventable cause of death in U.S.
• Sobering up

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