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Transcript
Perspectives in Nutrition, 8th Edition
Chapter 9 Outline: Energy Metabolism
After studying this chapter, you will be able to:
1. Explain the differences among metabolism, catabolism, and anabolism.
2. Describe aerobic and anaerobic metabolism of glucose.
3. Illustrate how energy is extracted from glucose, fatty acids, amino acids, and alcohol using
metabolic pathways, such as glycolysis, beta-oxidation, the citric acid cycle, and the electron
transport system.
4. Describe the role that acetyl-CoA plays in cell metabolism.
5. Identify the conditions that lead to ketogenesis and its importance in survival during fasting.
6. Describe the process of gluconeogenesis.
7. Discuss how the body metabolizes alcohol.
8. Compare the fate of energy from macronutrients during the fed and fasted states.
9. Describe common inborn errors of metabolism.
9.1
Metabolism: Chemical Reactions in the Body
A.
General
1.
Metabolism: entire network of chemical processes involved in maintaining life
a.
Release of energy from macronutrients
b.
Biosynthesis
c.
Prepare wastes for excretion
2.
Metabolic pathway: group of biochemical reactions that occur in sequence
a.
Anabolic: use small, simple compounds to build large, complex
compounds; growth
b.
Catabolic: break down compounds into smaller units; weight loss or
wasting
c.
In general, balance exists between anabolism and catabolism
3.
Intermediates: compounds formed within a metabolic pathway
B.
Energy for the Cell
1.
Uses
a.
Anabolism
b.
Muscle contraction
c.
Nerve conduction
d.
Ion pumps
2.
Sources: catabolic reactions that break chemical bonds in carbohydrate, fat,
protein, and alcohol (originally produced during photosynthesis) to form ATP,
heat, carbon dioxide, and water
3.
Adenosine Triphosphate (ATP)
a.
Main form of energy used by body
b.
Structure: adenosine bound to 3 phosphate groups
c.
The bonds between adenosine and phosphate groups contain energy
d.
C.
9.2
To release energy from ATP, hydrolysis of one phosphate yields
adenosine diphosphate (ADP) plus a free phosphate group, then
adenosine monophosphate (AMP) + Pi
e.
ATP is constantly recycled within cells
i.
Body contains 0.22 lb (100 g) of ATP
ii.
Sedentary adult uses 88 lb (40 kg) of ATP/d
iii.
During 1 hour of strenuous exercise, 66 lb (30 kg) of ATP are
used
Oxidation-Reduction Reactions: Key Processes in Energy Metabolism
1.
Oxidation-reduction reactions transfer electrons and hydrogen ions from energyyielding compounds to oxygen, forming water and energy for ATP synthesis
from ADP + Pi
2.
Oxidation and reduction occur together
a.
Inorganic substance is oxidized: loss of 1 or more electrons (LEO)
b.
Inorganic substance is reduced: gain of 1 or more electrons (GER)
c.
Organic substance is oxidized: gain of oxygen or loss of hydrogen;
hydrogen atoms are eventually added to oxygen to form water
d.
Organic substance is reduced: loss of oxygen or gain of hydrogen
3.
Oxidation-reduction reactions are controlled by enzymes (e.g., dehydrogenases)
4.
Coenzymes involved in dehydrogenase reactions
a.
Nicotinamide adenine dinucleotide (contains niacin)
i.
Oxidized form: NAD+
ii.
Reduced form: NADH
b.
Flavin adenine dinucleotide (contains riboflavin)
i.
Oxidized form: FAD
ii.
Reduced form: FADH2
ATP Production from Carbohydrates
A.
General
1.
Energy stored in foods is trapped in ATP or released as heat (maintains body
temperature)
2.
ATP is generated through cellular respiration: oxidation of food molecules to
obtain energy; oxygen is final electron acceptor
a.
Aerobic: oxygen is readily available; cellular respiration is more efficient
(net gain of 30 - 32 ATP from glucose)
b.
Anaerobic: oxygen is not present; cellular respiration is less efficient (net
gain of 2 ATP from glucose)
B.
Glycolysis (see Figure 9-7)
1.
Break down carbohydrates to generate energy: 1 glucose (6 carbons) is oxidized
to form 2 pyruvate (3 carbons), NADH + H+, and net of 2 ATP
2.
Provide building blocks for synthesis of other compounds
3.
Occurs in cytosol
C.
Synthesis of Acetyl CoA (see Figure 9-7)
Pyruvate is oxidized and joined with CoA to form acetyl-CoA, NADH + H+, and
CO2
2.
Catalyzed by pyruvate dehydrogenase
3.
Irreversible transition reaction
4.
Occurs in mitochondria
5.
Requires four B-vitamins
a.
Thiamin
b.
Riboflavin: FADH or FADH2
c.
Niacin: NAD+ or NADH
d.
Panthothenic acid: precursor to CoA
Citric Acid Cycle (see Figure 9-8)
1.
Alternate names for citric acid cycle
a.
Tricarboxylic acid (TCA) cycle
b.
Krebs cycle
2.
Acetyl-CoA leads to production of NADH + H+, FADH2, ATP, and CO2
3.
Occurs in mitochondria
4.
Does not require oxygen
5.
Two cycles per glucose molecule
6.
Each cycle yields
a.
2 CO2
b.
1 GTP (potential for ATP)
c.
3 NADH + H+
d.
1 FADH2
Electron Transport Chain (see Figure 9-10)
1.
NADH + H+ are oxidized to NAD+, and FADH2 is oxidized to FAD to produce
ATP and water
2.
Occurs in mitochondria
3.
Produces 90% of ATP from glucose
4.
As electrons are passed from one carrier to the next, small amounts of energy are
released (oxidative phosphorylation)
5.
Requires minerals
a.
Copper: component of enzyme
b.
Iron: component of cytochromes (electron-transfer compound)
The Importance of Oxygen
1.
NADH + H+ and FADH2 from citric acid cycle are regenerated to NAD+ and
FAD by transfer of their electrons and hydrogen to oxygen in the electron
transport chain
2.
Without oxygen, cells would not be able to generate sufficient energy to sustain
life
Anaerobic Metabolism
1.
For cells that are not capable of aerobic respiration (lack mitochondria; e.g.,
RBCs) or need to produce energy in the absence of oxygen (e.g., during intense
1.
D.
E.
F.
G.
H.
9.3
exercise), pyruvate may be converted to lactate, providing only 5% of potential
ATP (2 ATP)
2.
Transfer of hydrogen from NADH + H+ to pyruvate produces lactate + NAD+
3.
NAD+ continues function of glycolysis
4.
Lactate is released into bloodstream, picked up by liver, and used to synthesize
pyruvate, glucose, or some other intermediate in aerobic respiration
5.
Buildup of lactate in exercising muscle makes it difficult for muscles to contract
Overall energy yield of aerobic respiration
1.
Each NADH yields 2.5 ATP
2.
Each FADH2 yields 1.5 ATP
3.
Total ATP from each glucose molecule = 32 ATP
a.
Glycolysis  2 ATP
b.
Citric acid cycle (GTP)  2 ATP
c.
Citric acid cycle (ATP)  28 ATP
ATP Production from Fats
A.
General
1.
Lipolysis: breakdown of triglycerides into free fatty acids and glycerol
2.
Fatty acid oxidation: breakdown of fatty acids for energy production; net
donation of electrons from fatty acids to oxygen; takes place in mitochondria
3.
Sources of fatty acids for oxidation
a.
Dietary fat (e.g., following high-fat meal)
b.
Fat stored in adipose tissue (e.g., in fasting state)
4.
Release of fat from adipose cells relies on hormone-sensitive lipase
5.
Hormone-sensitive lipase activity is affected by:
a.
Glucagon (increases HSL activity)
b.
Growth hormone (increases HSL activity)
c.
Epinephrine (increases HSL activity)
d.
Insulin (decreases HSL activity)
6.
Fatty acids are shuttled from cytosol into mitochondria by carnitine
B.
ATP Production from Fatty Acids
1.
Most fatty acids in nature have even number of carbons (2 to 26)
2.
Beta-oxidation: 2-carbon fragments from a fatty acid are cleaved and converted
to acetyl-CoA (see Figure 9-13)
3.
Acetyl-CoA enters citric acid cycle to produce CO2 and ATP
a.
Glucose yields 30 - 32 ATP (5 ATPs/carbon)
b.
16-carbon fatty acid yields 104 ATP (7 ATPs/carbon, due to more
carbon-hydrogen bonds)
4.
A fatty acid with an odd number of carbons forms a 3-carbon compound
(propionyl-CoA), which bypasses the acetyl-CoA step when it enters the citric
acid cycle to yield NADH + H+ and FADH2 or can be used to synthesize other
products (e.g., glucose)
C.
Carbohydrate Aids Fat Metabolism
1.
D.
E.
F.
9.4
Some intermediates of citric acid cycle enter other biosynthetic pathways, which
depletes oxaloacetate supply
2.
Formation of pyruvate from carbohydrate metabolism replenishes oxaloacetate
Ketogenesis
1.
Ketone bodies: products of incomplete fatty acid oxidation, mostly resulting from
hormonal imbalances (e.g., inadequate insulin production)
a.
Acetoacetic acid
b.
Beta-hydroxybutyric acid
c.
Acetone
2.
Ketosis: excess of ketone bodies (see Figure 9-15)
a.
Decreases pH of body fluids
b.
Characterized by fruity breath odor (from excretion of acetone via lungs)
3.
Most ketone bodies are converted back into acetyl-CoA and metabolized via
citric acid cycle
Ketosis in Diabetes
1.
Lack of insulin inhibits normal carbohydrate and fat metabolism
2.
Cells cannot utilize glucose, so fatty acids are rapidly metabolized to ketone
bodies
3.
Excessive ketones are excreted in urine along with sodium and potassium,
leading to ion imbalances
4.
Diabetic ketoacidosis (typically only seen with uncontrolled type 1 diabetes)
a.
pH of blood decreases
b.
May lead to coma or death
c.
Treatment: insulin, electrolytes, fluids
Ketosis in Semistarvation or Fasting
1.
Low insulin production during semistarvation or fasting causes fatty acids to
flood the bloodstream and form ketone bodies in the liver
2.
Ketone bodies may be used for fuel by heart, muscles, kidneys, and brain (after
several days)
3.
As cells adapt to using ketones for fuel, less glucose is produced from amino
acids (sparing protein)
4.
Death occurs after 50 - 70 days of total fasting, when about half of body protein
is depleted
Protein Metabolism
A.
General
1.
Metabolism of protein takes place primarily in the liver
2.
Muscle metabolism of protein is limited to branched-chain amino acids (leucine,
isoleucine, and valine)
3.
Deamination: removal of amino group from amino acid; often requires vitamin
B-6
4.
Produces carbon skeletons that serve as intermediates in citric acid cycle or yield
acetyl-CoA or pyruvate
B.
C.
D.
Gluconeogenesis: Producing Glucose from Glucogenic Amino Acids and Other
Compounds
1.
Gluconeogenesis: production of glucose from certain amino acids in liver and
some kidney cells
2.
In the mitochondria, carbon skeleton of a glucogenic amino acid is converted to
oxaloacetate
3.
Oxaloacetate moves to cytosol, loses 1 CO2, becomes phosphoenolpyruvate
4.
Phosphoenolpyruvate reverses the path through glycolysis to glucose
5.
Gluconeogenesis requires ATP, biotin, riboflavin, niacin, and vitamin B-6
Gluconeogenesis from Typical Fatty Acids is Not Possible
1.
Fatty acids with even number of carbons are broken down to acetyl-CoA
2.
The reaction that converts pyruvate to acetyl-CoA is irreversible
3.
Acetyl-CoA may only form ketones and/or combine with oxaloacetate in the
citric acid cycle
4.
During citric acid cycle, acetyl-CoA is added to oxaloacetate, but 2 carbons are
lost as CO2; thus, no carbons from acetyl-CoA remain to form glucose
5.
Glycerol portion of triglyceride may be converted to glyceraldehyde 3-phosphate
to yield glucose; yield is insignificant
Disposal of Excess Amino Groups from Amino Acid Metabolism
1.
Amino groups (-NH2) are converted to ammonia (NH3),which is toxic to cells
2.
In the liver, ammonia is converted to urea by the urea cycle
a.
Urea is excreted via urine
3.
Nitrogen in blood is a sign of organ disease
a.
High [NH3] = liver disease
b.
High [urea] = kidney disease
9.5
Alcohol Metabolism (see Figure 9-18)
A.
Alcohol dehydrogenase (ADH) pathway is primary pathway for alcohol metabolism
1.
Alcohol  acetaldehyde by alcohol dehydrogenase; yields NADH + H+
2.
Acetealdehyde  acetyl-CoA by aldehyde dehydrogenase; yields NADH + H+
3.
Occurs mainly in liver, although 10 - 30% may occur in stomach lining cells
4.
Fate of acetyl-CoA
a.
Some may enter citric acid cycle, but ADH pathway limits supply of
NAD+; ADH pathway takes priority over citric acid cycle in cells
b.
Most is directed to fatty acid and triglyceride synthesis
i.
Results in steatosis: accumulation of fat in the liver
ii.
Characterized by high blood triglycerides
B.
Microsomal ethanol oxidizing system (MEOS) metabolizes alcohol intake in excess of
capacity of ADH pathway
C.
Catalase pathway is minor
D.
Exceeding capacity of alcohol metabolizing systems leads to alcohol poisoning
9.6
Regulation of Energy Metabolism
A.
B.
C.
D.
Overview of metabolic pathways
1.
Glycolysis (glucose  pyruvate) in cytosol
2.
Transition reaction (pyruvate  acetyl-CoA) in mitochondria
3.
Fatty acid oxidation (fatty acid  acetyl CoA) in mitochondria
4.
Glucogenic amino acid oxidation (amino acids  pyruvate) in cytosol
5.
Non-glucogenic amino acid oxidation (amino acids  acetyl-CoA) in
mitochondria
6.
Alcohol oxidation (ethanol  acetaldehyde) in cytosol
7.
Alcohol oxidation (acetaldehyde  acetyl-CoA) in mitochondria
8.
Citric acid cycle (acetyl-CoA  CO2) in mitochondria
9.
Gluconeogenesis in mitochondria and cytosol
The Liver (see Figure 9-20)
1.
Conversions between various simple sugars
2.
Fat synthesis
3.
Production of ketone bodies
4.
Amino acid metabolism
5.
Urea production
6.
Alcohol metabolism
7.
Nutrient storage
ATP Concentrations
1.
High [ATP] decreases energy-yielding reactions and increases anabolic reactions
2.
High [ADP] increases energy-yielding reactions and decreases anabolic reactions
Enzymes, Hormones, Vitamins, and Minerals
1.
Enzymes
a.
Presence (i.e., enzyme synthesis)
b.
Rate of activity
2.
Hormones
a.
Regulate metabolic processes
b.
Low [insulin] promotes gluconeogenesis, protein breakdown, and
lipolysis
c.
High [insulin] promotes synthesis of glycogen, fat, and protein
3.
Vitamins and minerals (see Figure 9-21)
a.
Thiamin
b.
Riboflavin
c.
Niacin
d.
Pantothenic acid
e.
Biotin
f.
Vitamin B-6
g.
Folate
h.
Vitamin B-12
i.
Iron
j.
Copper
9.7
Fasting and Feasting
A.
Fasting
1.
Postprandial fasting (0 - 6 hours after eating)
a.
Use of liver stores of carbohydrate (glycogen)
b.
Use of adipose stores of fatty acids
2.
Short-term fasting (3 - 5 days)
a.
Glycogen stores are depleted
b.
Fatty acid oxidation continues
c.
Gluconeogenesis (amino acids from lean tissue and glycerol from
triglycerides  glucose) to provide fuel for CNS and RBCs
i.
Early gluconeogenesis leads to rapid breakdown of lean tissue
(supplies 90% of glucose) that would lead to death within 2- 3
weeks
ii.
Sodium and potassium are also depleted via urine when ketone
bodies are excreted
iii.
Blood urea levels increase
3.
Long-term fasting (5+ days)
a.
Metabolic rate slows, reduces energy requirements
b.
CNS begins to use ketone bodies
c.
When lean body mass declines by 50% (7 - 10 weeks), death occurs
B.
Feasting
1.
Accumulation of body fat
2.
Insulin production encourages use of glucose for energy, synthesis of glycogen,
and storage of protein and fat
3.
Fat consumed in excess of need is stored in adipose cells (requires little energy)
4.
Protein consumed in excess of need does not promote muscle development
a.
Some remains in blood’s amino acid pool (minor)
b.
Some used to synthesize fatty acids (minor; costly process requires ATP,
biotin, niacin, and pantothenic acid)
c.
Some metabolized for energy
5.
Carbohydrate consumed in excess of need
a.
Maximize glycogen stores
b.
Used as fuel, lessens need for fatty acid oxidation
c.
Storage as fat (not an active pathway in humans; uses ATP, biotin,
niacin, and pantothenic acid)
6.
Synthesis of fat from carbohydrate or protein (lipogenesis) takes place in cytosol
of liver cells
a.
Acetyl-CoA from glucose or amino acids is linked into palmitic acid (16carbon fatty acid)
b.
Insulin increases activity of fatty acid synthase, which regulates
lipogenesis
c.
Palmitic acid can be lengthened to 18- or 20-carbon chain
d.
Used to synthesize triglycerides
9.8
Medical Perspective: Inborn Errors of Metabolism
A.
General
1.
Lack of enzyme to perform a specific metabolic function
2.
Products of disrupted metabolism may be toxic to the body
3.
Inherit defective gene from one or both parents (may not have the disease, but are
carriers)
4.
Symptoms of disorder appear shortly after birth (e.g., loss of appetite, vomiting,
dehydration, weakness, developmental delays)
5.
Specific - involve 1 or a few enzymes
6.
No cure, only treatment
B.
Newborn Screening
1.
Public health program that provides early identification and follow-up treatment
of infants with genetic and metabolic disorders
2.
Components of screening are state-specific
C.
Phenylketonuria (PKU)
1.
1/13,500 -19,000 births
2.
Most common among people of Irish descent
3.
Carriers are detected by simple blood test
4.
Newborn screening for PKU is required in all states
5.
Inefficient function of phenylalanine hydroxylase in liver
6.
Treatment
a.
Phenylalanine-restricted diet (phenylalanine cannot be omitted because it
is an essential amino acid)
b.
Continual monitoring of infants through blood testing
c.
Specialized infant formulas are needed to meet high protein needs
without high phenylalanine
d.
Foods with low phenylalanine content
i.
Fruits
ii.
Vegetables
e.
Foods with moderate phenylalanine content
i.
Breads
ii.
Cereals
f.
Foods with high phenylalanine content
i.
Dairy products
ii.
Eggs
iii.
Meats
iv.
Nuts
v.
Cheeses
vi.
Aspartame (artificial sweetener made with phenylalanine)
g.
Older children and adults must still rely on low-phenylalanine formula
7.
Low-phenylalanine diet must be continued throughout life or decreased
intelligence and behavioral problems occur
8.
D.
E.
During pregnancy, exposure to toxic levels of phenylalanine may lead to
miscarriage or birth defects
Galactosemia
1.
1/47,000 births
2.
Most common among people of Italian and Irish descent
3.
2 specific enzyme defects lead to reduced metabolism of galactose to glucose;
buildup of galactose can lead to serious bacterial infections, mental retardation,
and cataracts
4.
Infants with galactosemia develop vomiting after a few days of infant formula or
breast milk
5.
Treatment
a.
Soy formula
b.
Avoidance of certain foods
i.
Lactose-containing products
ii.
Organ meats
iii.
Some fruits and vegetables
c.
Strict label reading
Glycogen Storage Disease
1.
1/60,000 births
2.
Inability to convert glycogen to glucose due to one of a number of enzyme
defects
3.
Symptoms
a.
Poor growth
b.
Low blood glucose
c.
Liver enlargement
4.
Treatment
a.
Frequent meals to regulate blood glucose
b.
Raw cornstarch (slowly digested, maintains blood glucose)
c.
Careful monitoring of blood glucose