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Metabolism
How do we derive energy from food, and what do we do with that energy?
Catabolism
Breaking down macronutrients for energy and other reasons
Carb metabolism--glycogenolysis, glycolysis, TCA cycle, electron transfer
chain
Fatty acid beta-oxidation
Protein breakdown
Anabolism
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Building up body components
Requires energy
Glycogenesis
Gluconeogenesis
Fatty acid synthesis
Protein synthesis
High energy compounds
Adenosine triphosphate (ATP)
Guanosine triphosphate (GTP)
Nicotinamide adenine dinucleotide (NADH)
Nicotinamide adenine dinucleotide phosphate (NADPH)
– Both NADH and NADPH contain niacin
Flavin adenine dinucleotide (FADH2)
– Contains riboflavin
Carbohydrate metabolism
Glycolysis-glucose to pyruvate
Pyruvate to acetyl coA
Krebs/TCA/citric acid cycle
Electron transport chain
Glycolysis…
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Is anaerobic
Occurs in the cytoplasm of all cells
Takes 1 molecule of glucose to 2 molecules of pyruvate
Yield: 2 NADH + 4 ATP, but 2 ATP used at beginning of pathway
Pyruvate
Acetyl coA
Occurs in mitochondria with an enzyme complex that utilizes thiamin as a
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coenzyme
Coenzyme A is derived from pantothenic acid
2 molecules pyruvate from 1 molecule glucose yields 2 NADH and 2 acetyl co
A molecules
Requires oxygen
If oxygen isn’t available
Pyruvate is converted to lactate
Can be converted back to pyruvate when at rest, or can be converted to
glucose in liver (gluconeogenesis)
This can occur in muscle during strenuous exercise
Citric Acid Cycle
citrate
Acetyl coA + oxaloacetate
Produces 2 CO2 molecules
Also produces 6 NADH, 2 FADH2 + 2 GTP per each original molecule of
glucose (2 acetyl coA)
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Electron transport chain
Where NADH and FADH2 are converted to ATP
1 molecule NADH from citric acid cycle = 2.5 ATP
1 molecule FADH2 = 1.5 ATP
Oxygen is required
Water is produced
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What about the NADH’s from glycolysis?
Yield either 1.5 or 2.5 molecules ATP
Electrons have to be shuttled into the mitochondrion
So we can only give an approximate range of ATP yield
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The bottom line from one glucose molecule
Glycolysis: 2 ATP, 3-5 ATP from NADH
Pyruvate to acetyl coA: 5 ATP from NADH
Citric acid cycle: 2 GTP, 3 ATP from 2 FADH, 15 ATP from 6 NADH
Grand total: 30-32 ATP
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You have to spend energy to make energy
Glycolysis takes 2 ATP in beginning steps
The equivalent of 2 ATP is needed to start beta-oxidation of fat
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Beta-oxidation of fatty acids
Occurs in mitochondria, requires oxygen
Fatty acids are shuttled into mitochondria by carnitine
Fatty acid must be activated by coA
– ATP
AMP + 2P
– Successive acetyl coA’s clipped off
– 1 FADH2 + 1 NADH produced/clip
The bottom line for beta-oxidation of stearic acid (C18:0)
20 ATP from 8 NADH
12 ATP from 12 FADH2
9 acetyl coA’s through the citric acid cycle: 9 GTP, 67.5 ATP from 27 NADH
and 13.5 ATP from 9 FADH2
Minus 2 ATP to start beta oxidation:
120 ATP
Fat burns in a flame of carbohydrate
Carbohydrate is needed
Without sufficient oxaloacetate from carb to drive the citric acid cycle, the
acetyl coA from fatty acid beta-oxidation is converted to ketones
ketosis
Ketogenesis-Occurs in Liver
Two molecules of acetyl coA combine to form acetoacetate
Acetoacetate exists in equilibrium with another ketone, beta-hydroxybutyrate
Acetoacetate can be used as energy source for many tissues, but not for…
Ketones can be used as brain fuel in a pinch
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What about protein?
Amino acids can be used for energy once amine groups are removed
Some amino acid skeletons (keto acids) are converted to pyruvate or citric
acid cycle intermediates--glucogenic amino acids
Ketogenic amino acids are converted to acetyl coA
ATP yield for amino acids is variable
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Under normal conditions, protein is not metabolized for energy
Only during late starvation and stress is protein used as an energy source
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Gluconeogenesis
Used when glucose is limited and brain/red blood cells are in need
Problem: several steps in glycolysis and citric acid cycle are irreversible
Solution: separate enzymes get around these blocks
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Reminder
You cannot make glucose from fatty acids or acetyl coA
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Lactate
Glucose
Conversion in liver via the Cori cycle
(Gerty Cori was the first woman to win a Nobel prize in medicine for this
discovery)
Fatty Acid Synthesis-Lipogenesis
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Occurs in cytosol
NOT a reversal of beta-oxidation
Lipogenesis utilizes energy in the form of NADPH
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Can carbs make me fat?
Yes, but not the way you think
Excess carb Calories in the diet spare fat from being used for energy
A small amount of carb may be converted to triglycerides
Hormonal Control of Metabolism
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Insulin
Glucagon
Epinephrine-stimulates glycogenolysis during the fight or flight response
Cortisol-promotes protein catabolism for gluconeogenesis in times of
prolonged stress (surgery, injury)
Real-Life Situations
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Feasts
Fasts
Starvation
Stress
(see figs 7-22 through 7-25)
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Feasting
Insulin rules, glucagon, epinephrine, and cortisol suppressed
Anabolism--glycogen stores replenished
Refill amino acid pool
Excess energy stored as fat
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A Short-Term Fast
(overnight or up to 2 days)
Glucagon rules; insulin is suppressed
Glycogenolysis occurs to keep brain and red blood cells fed
As glycogen stores are depleted, fatty acids are burned as fuel
A little gluconeogenesis from free amino acids occurs
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Longer-term fasting
(up to ~ 1 week)
Insulin secretion is still suppressed
Gluconeogenesis from free amino acids and glycerol
Fatty acid beta-oxidation
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Hunger-Strike Fasting
(à la David Blaine)
Ketones begin to supply energy to brain as free amino acids decline
Body begins energy conservation measures
Some brain cells are still dependent on glucose, so a little gluconeogenesis
occurs from protein catabolism
Late-Stage Starvation
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Fat stores depleted
Protein catabolism picks up slack--muscles atrophy
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Physiological Stress
Epinephrine and cortisol enter picture big time, along with glucagon
Cortisol inhibits fat tissue breakdown, so energy needs are met by protein
once glycogen is depleted
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Energy Balance
Calories ingested - Calories expended
Energy Balance
If result of equation is + over time (and you’re a nonpregnant adult), you may
gain weight
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If result of equation is - over time, you may lose weight
Calories in--control of intake
physiological cues
Hunger
Satiation
Satiety
Appetite-psychological cue
Control of Physiological Cues
Diet composition--high fiber vs. low fiber
Gut sensation of fullness
Ambient temperature
Hormones
– Insulin suppresses synthesis of neuropeptide Y
– Leptin
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Then we have the environmental and social influences
Time of day
Social situation
Emotional situation
Availability of food
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Components of Energy Expenditure
Resting metabolic rate
Thermic effect of food
Physical activity
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Resting Metabolic Rate
The Calories needed for involuntary functions
– Breathing
– Pumping blood
– Protein turnover
– Neurological activity
– Temperature regulation
RMR is controlled by thyroid gland
Thyroid hormone (thyroxine)
Influences on RMR
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Age
Gender
Height
Amount of lean body mass (muscle)
Fever, infection
Fasting, malnutrition
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Thermic Effect of Food
Increase in metabolic rate from ingesting, digesting and absorbing food
A minor contributor to total energy expenditure
Physical Activity
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The most variable component
– Sedentary
– Moderate activity
– Heavy activity
– Exceptional activity
Direct measurement of energy expenditure--Calorimetry
Direct--person resides in a controlled chamber
Indirect--measurement of oxygen in and carbon dioxide out
Doubly labeled water--expensive, but a good measurement
Do the math!
Convert your weight to kg (lb/2.2)
If male, multiply wt x 1.0 Cal/kg/hr x 24 hr
If female, wt x 0.9 Cal/kg/hr x 24 hr
Adjust by physical activity (see table 8.4)
– Sedentary x 1.2-1.3
Light x 1.3-1.45
– Moderate x 1.45-1.65
Heavy x 1.65-1.9
– Exceptional x 1.9-2.2
Example 1
A 35-yr-old man who works in front of a computer for 10+ hr/day; parks next to
his building; physical activity consists of going from recliner to fridge to recliner
on weekends
Wt: 176 lb., or 80 kg (176 /2.2)
80 x 1 x 24 = 1920 x 1.2-1.3 = 2300-2500
Example 2
• 21 yr old female; physical therapy major at UW; in training for triathlons in
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November & December; also works at gym as a trainer
Wt: 125 lb. /56.8 kg
Basal Calories:
Activity level:
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How to Calculate Ideal Body Weight
Males: 106 lb for 1st 5’ of ht, then 6 lb for each in over 5’
Females: 100 lb for 1st 5’ of ht, then 5 lb for each in over 5’
Add 10% for a large frame
Subtract 10% for a small frame
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Assessing body composition
Weight--may not tell you much
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Body mass index = wt (lb)/ht (in)2 x 704.5
[or wt (kg)/ht (m)2]
Also may not tell you much
What does the BMI # mean?
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< 16 Too lean
16-19.9 Lean, maybe underweight
20-24.9 Desirable
25-29.9 Overweight
30-34.9 Grade I obesity
35-39.9 Grade II obesity
≥ 40 Morbidly obese
Estimates of body fat distribution
Waist-hip ratio-high risk numbers
– > 0.8 in women
– > 0.9 in men
Waist circumference-preferable numbers
– < 35” for women
– <40” for men
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Measuring body fat
Densitometry--underwater weighing
Air displacement--the Bod Pod
Skinfold thickness
DEXA
Bioelectrical impedance
MRI or CT scan
Too much vs. too little body fat
Both extremes can be hazardous to health
Both are at high risk in hospital situation
Women with too little body fat may have abnormal or absent menstrual
periods, which may predispose them to early bone loss
Patterns of Body Fat
Gynoid (pears)--fat concentrated below waist
– Seen mostly in premenopausal females
Android (apples)--fat concentrated in trunk
– Seen mostly in men
Obesity
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The plague of an affluent society
Current obesity risk factors
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Genetics
– The “thrifty gene” hypothesis
Environment
Age and lifestyle
Gender
Weight Management
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Reduced intake
– 1 lb fat = 3500 Calories
Increased exercise
Behavioral change
Medication
Surgery
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Eating Disorders
“You can never be too rich or too thin”
The Duchess of Windsor
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Eating Disorders
Psychiatric disorder with medical & nutritional implications
Men can also be affected
Can be related to incidents of abuse, perfectionistic parents, chaos at home
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Eating Disorders≠Disordered Eating
Eating disorders are illnesses that interferes with daily living
Disordered eating is usually temporary
– For example, high school and college wrestlers
– However, can evolve into full-blown eating disorders
Anorexia Nervosa
Starving oneself to attain a certain body image
Sufferers want to be in control of something
Some also have obsessive-compulsive disorder
Behavior Patterns in Anorexia Nervosa
Restrictors-simply don’t eat enough food
Restrict and purgers-may get rid of food via vomiting, laxative or diuretic
(“water pill”) abuse
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Consequences of Anorexia Nervosa (*females)
Fat store depletion, muscle wasting
Reduced estrogen production*
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Amenorrhea
Reduced bone density
Male body hair pattern
More consequences of AN
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Hair loss, dry skin
Reduced blood pressure, pulse, respiration
Dehydration
Electrolyte (Na, K) imbalances
Death due to heart failure
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Treatment
Unfortunately, relapse rate is high
Requires team approach--MD’s (psychiatrist and pediatrician or internist),
nurses, dietitians
Patients must be refed very slowly
Monitor Calories, not weight gain
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Bulimia
Patient at or near ideal body weight
About 1/2 of anorexics become bulimic
Binging followed by purging
Preoccupation with body weight
Consequences--tooth damage, swollen salivary glands, electrolyte imbalance
Also needs team approach to therapy
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Binge Eating Disorder
A relatively new diagnosis in the manual of psychiatry
Person eats massive amounts of Calories at a sitting WITHOUT purging at
least 2 days a week for 6 months
Binges accompanied by guilt and shame
FOOD IS AN ADDICTIVE DRUG