Chapter 19
Regulation of
Metabolism
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19-1
Nutritional Requirements
Living
tissue is maintained by constant expenditure of
energy (ATP)
ATP derived from glucose, fatty acids, ketones, amino
acids, and others
Energy of food is commonly measured in kilocalories (1
kcal = 1000 calories)
Carbohydrates and proteins yield 4kcal/gm; fats-9kcal/gm
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19-4
Metabolic Rate and Caloric Requirements
Metabolic
rate (MR) is total rate of body metabolism
= amount of O2 consumed by body/min
Basal metabolic rate (BMR) is MR of awake relaxed person
12–14 hrs after eating and at a comfortable temperature
BMR depends on age, sex, body surface area, activity level,
and thyroid hormone levels
Hyperthyroids have high BMR; hypothyroids have low
BMR
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19-5
Metabolism
Is
all chemical reactions in body
Includes synthesis and energy storage reactions (anabolism);
and energy liberating reactions (catabolism)
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19-6
Anabolic Requirements
Anabolic
reactions synthesize DNA and RNA, proteins, fats,
and carbohydrates
Must occur constantly to replace molecules that are
hydrolyzed in catabolic reactions
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19-7
Turnover Rate
Is
rate at which a molecule is broken down and
resynthesized
Average turnover for Carbs is 250 g/day
Some glucose is reused so net need ~150 g/day
Average turnover for protein is 150 g/day
Some is reused for protein synthesis so net need ~35
g/day
9 essential amino acids must be supplied in diet because
can't be synthesized
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19-8
Turnover Rate continued
Average
turnover for fats is 100 g/day
Little is required in diet because can be synthesized from
Carbs
2 essential fatty acids must be supplied in diet
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19-9
Vitamins
Are
small organic molecules that serve as coenzymes in
metabolism or have highly specific functions
Must be obtained in diet because body does not produce
them, or does so in insufficient amounts
Can be placed in 2 classes
Fat-solubles include A, D, E, and K
Water-solubles include B1, B2, B3, B6, B12, pantothenic
acid, biotin, folic acid, and vitamin C
Serve as coenzymes in metabolism
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19-10
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19-11
Minerals (Elements)
Are
needed as cofactors for specific enzymes and other
critical functions
Sodium, potassium, magnesium, calcium, phosphate, and
chloride are needed daily in large amounts
Iron, zinc, manganese, fluorine, copper, molybdenum,
chromium, and selenium are trace elements required in small
amounts/day
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19-12
Free Radicals
Are
highly reactive and oxidize or reduce other atoms
Because have an unpaired electron in their outer orbital
The major free radicals are reactive oxygen or reactive
nitrogen species
Because contain oxygen or nitrogen with unpaired
electron
Include NO radical, superoxide radical, and hydroxyl
radical
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19-13
Free Radicals continued
Serve
important physiological functions
Help to destroy bacteria
Can produce vasodilation
Can stimulate cell proliferation
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19-14
Free Radicals continued
In
excess can exert oxidative stress contributing to disease
states
Can damage lipids, proteins, and DNA
Promote apoptosis, aging, inflammatory disease,
degenerative, and other diseases and malignant growth
Underlying cause is widespread production of
superoxide radicals by mitochondria
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19-15
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19-17
Control of Adipose Tissue Levels
Body
appears to have negative feedback loops (an adipostat)
to defend maintenance of a certain amount of adipose tissue
Adipose cells (adipocytes) store and release fat under
hormonal control
And may release their own hormone(s) to influence
metabolism
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19-20
Endocrine Functions of Adipocytes
Adipocytes
secrete regulatory hormones called adipokines
when their PPARg receptors are activated
Regulate hunger, metabolism, and insulin sensitivity
E.g., cause muscle to become more responsive to
insulin
Include adiponectin, leptin, resistin, TNF, and retinol
BP4
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19-22
Endocrine Functions of Adipocytes cont.
The
adipocyte hormones TNFa, resistin, retinol BP4, and
leptin are increased in obesity and Type II diabetes
All appear to reduce sensitivity of muscle to insulin
(insulin resistance)
Leptin signals the hypothalamus on how much fat is
stored, thereby regulating hunger and food intake
Adiponectin is decreased in obesity and Type II diabetes
has an insulin-sensitizing, antidiabetic effect
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19-23
Low Adiposity: Starvation
Starvation
and malnutrition diminish immune function
Low adipose levels cause low leptin levels
Helper T cells have leptin receptors
 Thus, low leptin can lead to diminished immune
function
Leptin may play role in timing of puberty and in the
amenorrhea of underweight women
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19-24
Obesity
Childhood
obesity involves increases in both size and
number of adipocytes
Weight gain in adulthood is due mainly to increase in
adipocyte size
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19-25
Obesity continued
Obesity
is often diagnosed by using using a body mass index
(BMI)
BMI = w/h2
w = weight in kilograms
h = height in meters
Healthy weight is BMI between 19 – 25
Obesity defined as BMI > 30
60% of pop in US is either overweight (BMI>25) or obese
(BMI>30)

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19-26
Regulation of Hunger
Is
at least partially controlled by hypothalamus
Lesions in ventromedial area produce hyperphagia and
obesity in animals
Lesions in lateral area produce hypophagia
Involves a number of NTs: endorphins (promote
overeating), Norepi (promotes overeating), serotonin
(suppresses overeating)
Very successful diet pills Redux and fen-phen worked by
elevating brain serotonin
(Now banned because of heart valve side effects)
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19-27
Regulation of Hunger: Signals from Stomach
and SI
Involves polypeptide hormones
secreted by the stomach and
SI
Ghrelin
stimulates hunger via effect in arcuate
Secreted by stomach at high levels when stomach is
empty and low levels when full
CCK from SI promotes satiety
Released during digestion
Levels rise during and immediately after a meal
Ghrelin and CCK regulate hunger on short-term, meal-tomeal basis
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19-29
Regulation of Hunger continued
Is
influenced by leptin--a satiety factor secreted by
adipocytes and involved in long-term regulation
Secretion increases as stored fat increases
Signals body's level of adiposity
Acts in arcuate to suppress Neuropep Y and agoutirelated peptide; and stimulate MSH
Insulin may play role in satiety
Suppresses Neuropep Y
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19-31
Calorie Expenditure of Body
Has
3 components:
Number of calories used at the BMR make up 60% of
total
Number used in response to temperature changes and
during digestion/absorption (adaptive thermogenesis)
make-up 10% of total
Starvation can lower MR 40%; eating raises MR 2540% (thermic effect of food)
Number used during physical activity depends on type
and intensity
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19-33
Hormonal Regulation of Metabolism
 Balance
between
anabolism and
catabolism
depends on
levels of
insulin,
glucagon, GH,
thyroxine, and
others
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19-35
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19-36
Pancreatic Islets of Langerhans
Contain
2 cell types involved in energy homeostasis:
α cells secrete glucagon when glucose levels are low
Which causes increased glucose by stimulating
glycogenolysis in liver
β cells secrete insulin when glucose levels are high
Which reduces blood glucose by promoting its uptake
by tissues
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19-39
Insulin and Glucagon Secretion
Normal
fasting glucose
level is 65–105 mg/dl
Insulin and glucagon
normally prevent
levels from rising
above 170mg/dl after
meals or falling
below 50mg/dl
between meals
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19-40
Insulin
Overall
effect is to promote anabolism
Promotes storage of digestion products
Inhibits breakdown of fat and protein
Inhibits secretion of glucagon
Stimulates insertion of GLUT4 transporters in cell
membrane of skeletal muscle, liver, and fat
Transports by facilitated diffusion
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19-41
Glucagon
Maintains
blood glucose concentration above 50mg/dl
Stimulates glycogenolysis in liver
Stimulates gluconeogenesis, lipolysis, and ketogenesis
Skeletal muscle, heart, liver, and kidneys use fatty acids
for energy
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19-43
Effects of ANS on Insulin and Glucagon
ANS
innervates islets
Activation of Parasymp NS stimulates insulin secretion
Activation of Symp NS stimulates glucagon and inhibits
insulin
This can cause "stress hyperglycemia"
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19-45
Diabetes Mellitus
Characterized
by chronic high blood glucose levels
(hyperglycemia)
Type I (insulin dependent or IDDM) is due to insufficient
insulin secretion
5% of diabetics are this type
Type II (insulin independent or NIDDM) is due to lack of
effect of insulin
95% of diabetics are this type
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19-49
Type I Diabetes
β
cells of islets are progressively destroyed by autoimmune
attack by killer T lymphocytes
Glucose is unable to enter resting muscle or adipose cells
Rate of fat synthesis lags behind rate of lipolysis
Fatty acids are converted to ketone bodies, producing
ketoacidosis
Increased glucagon levels stimulate glycogenolysis in liver
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19-51
Effects of Uncontrolled Type I Diabetes
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19-52
Metabolic Effects of Cortisol
Cortisol
is secreted in response to ACTH
Which is often released in response to stress, including
fasting and exercise
Where it supports effects of glucagon
Promotes lipolysis, ketogenesis, and protein
breakdown
 Protein breakdown increases amino acid levels for
use in gluconeogenesis in liver
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19-58
Metabolic Effects of Cortisol continued
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19-59
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19-63
Growth Hormone and Body Growth
Growth
of skeleton occurs first as growth of cartilage at
epiphyseal discs which then become converted to bone
Mediated by IGF-1 and 2 which stimulate chondrocytes
to divide and secrete more cartilaginous matrix
Growth stops when epiphyseal discs are ossified
Gigantism produced by excess GH secretion in children
Dwarfism caused by inadequate secretion of GH during
childhood
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19-64
1,25 Vitamin D3
Synthesis
begins in skin when cholesterol derivative is
converted to Vit D3 by sunlight
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19-75
1,25 Vitamin D3 continued
stimulates intestinal absorption of Ca2+ and PO43Directly stimulates bone reabsorption by promoting
formation of osteoclasts
Stimulates kidney to reabsorb Ca2+ and PO43
Simultaneously raising Ca2+ and PO43- results in increased
tendency of these to precipitate as hydroxyapatite
Stimulated by PTH
Inadequate Vit D in diet and body causes osteomalacia and
rickets (loss of bone calcification)
Directly
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19-76