Transcript Vitamin D 3 - McGraw

Chapter 19
Regulation of Metabolism
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Nutritional Requirements
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Living tissue is maintained by constant
expenditure of energy (ATP).
Indirectly from glucose, fatty acids, ketones,
amino acids and other organic molecules.
Energy of food is commonly measured in
kilocalories.
One kilocalorie is = 1000 calories.
One calorie = amount of heat required to
raise the temperature of 1 cm3 of H20 from
14.5o to 15.5o C.
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Metabolic Rate and Caloric
Requirements
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Metabolic rate measured by the amount of
oxygen consumed by the body/min.
BMR:
Oxygen consumption of an awake relaxed
person 12 – 14 hours after eating and at a
comfortable temperature.
BMR determined by:
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Age.
Gender.
Body surface area.
Thyroid secretion.
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Anabolism
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Synthesis (build up):
Synthesize:
DNA and RNA.
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Proteins.
Triglycerides.
Glycogen.
Must occur constantly to replace
molecules that are hydrolyzed.
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Catabolism
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Hydrolysis (break down):
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Hydrolysis reactions and cellular
respiration.
Gluconeogenesis.
Glycogenolysis.
Lipolysis.
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Turnover Rate
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Rate at which a molecule is broken down and
resynthesized.
Average daily turnover for carbohydrates is
250 g/day.
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Average daily turnover for protein is 150
g/day.
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Only need about 150 g/day.
Only need 35 g/day.
Average daily turnover for fats is 100 g/day.
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Little is actually required in the diet.
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Vitamins and Minerals
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Small organic molecules that serve as
coenzymes in metabolic reactions or have
highly specific functions.
Must be obtained from the diet because the
body does not produce them, or does so in
insufficient amounts.
Certain vitamins function as antioxidants.
2 classes of vitamins:
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Fat-soluble
Water-soluble
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Vitamins
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Water-soluble vitamins:
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Serve as coenzymes in the metabolism of
carbohydrates, lipids, and proteins.
May serve as antioxidants.
Fat-soluble vitamins:
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Serve as antioxidants.
Bind to nuclear receptors.
Involved in regulating fetal development.
Regulate Ca++ balance.
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Minerals
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Needed as cofactors for specific
enzymes and other critical functions.
Trace elements:
Required in small amounts from 50 mg
to 18 mg/day.
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Free Radicals and
Antioxidants
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Electrons are located in orbitals.
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Free radical:
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Each orbital contains a maximum of 2 electrons.
When an orbital has an unpaired electron.
Highly reactive in the body.
Oxidize other atoms or reduce other atoms.
Major free radicals called:
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Reactive oxygen or nitrogen species.
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Oxygen or nitrogen as unpaired electron.
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Free Radicals and
Antioxidants
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Functions of free radicals:
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Help to destroy bacteria.
Produce vasodilation.
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NO, superoxide radical, and hydroxy radical.
Exert oxidative stress contributing to disease
states.
Antioxidants:
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Protective mechanism against oxidative stress.
Can react with free radicals by picking up unpaired
electrons.
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Glutathione, vitamin C, and vitamin E.
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Regulation of Energy
Metabolism
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Energy reserves:
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Molecules that
can be oxidized for
energy are derived
from storage
molecules.
Circulating
substrates:
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Molecules absorbed
through small
intestine and carried
to the cell.
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Regulatory Functions of
Adipose Tissue
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Adiposat:
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Negative feedback loops to defend amount of
adipose tissue.
Differentiation of adipocytes require nuclear
receptor protein PPARg which is activated
when bound to 15-D PGJ2.
Stimulate adipogenesis by promoting
development of preadipocytes into mature
adipocytes.
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Regulatory Functions of
Adipose Tissue
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Adipocytes secrete regulatory molecules.
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Leptin:
 Hormone that signals the hypothalamus to indicate the
level of fat storage.
 Satiety factor in obese have decreased sensitivity to
leptin.
 Neuropeptide Y is a potent stimulator of appetite. These
neurons are inhibited by leptin.
TNFa:
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Acts to reduce the sensitivity of cells to insulin.
Increased in obesity.
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Obesity
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Obesity is often diagnosed by using using a
body mass index (BMI).
BMI = w
h2
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W = weight in kilograms
H = height in meters
Obesity in childhood is due to an increase in
both the size and the # of adipocytes.
Obesity defined as BMI > 30.
Healthy weight as BMI between 19 – 25.
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Hormonal Regulation of
Metabolism
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Absorptive state:
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Absorption of energy.
4 hour period after eating.
Increase in insulin secretion.
Postabsorptive state:
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Fasting state.
At least 4 hours after the meal.
Increase in glucagon secretion.
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Balance Between Anabolism
and Catabolism
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The rate of deposit
and withdrawl of
energy substrates and
the conversion of 1
type of energy
substrate into another
are regulated by
hormones.
Antagonistic effects of
insulin, glucagon, GH,
T3, cortisol, and
epinephrine balance
anabolism and
catabolism.
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Energy Regulation of
Pancreas
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Islets of Langerhans contain 3
distinct cell types:
a: glucagon.
 b: insulin.
 D: somatostatin.
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Regulation of Insulin and
Glucagon
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Mainly regulated by plasma [glucose].
Lesser effect: plasma [amino acid].
Regulated by negative feedback.
Glucose enters the brain by facilitated
diffusion.
Normal fasting [glucose] is 65 – 105
mg/dl.
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Regulation of Insulin and
Glucagon
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Increased plasma [glucose].
Glucose binds to GLUT2 receptor protein in b
cells stimulating the production and release of
insulin.
Insulin:
Stimulates skeletal muscle cells and
adipocytes to incorporate GLUT4 (glucose
facilitated diffusion carrier) into plasma
membranes.
Promotes anabolism.
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Oral Glucose Tolerance Test
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Measurement of
the ability of beta
cells to secrete
insulin and ability
of insulin to lower
blood glucose.
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Regulation of Insulin and
Glucagon
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Parasympathetic Nervous System:
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Sympathetic Nervous System:
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Stimulate insulin secretion.
GLP-1:
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Stimulate glucagon secretion.
GIP:
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Stimulate insulin secretion.
Stimulate insulin secretion.
CCK:
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Stimulate insulin secretion.
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Regulation of Insulin and
Glucagon Secretion
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Absorptive State
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Insulin is the major hormone that promotes
anabolism in the body.
Plasma [insulin] increases.
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Promotes cellular uptake of plasma glucose.
Stimulates glycogen storage in the liver and
muscles.
Stimulates triglyceride storage in adipose cells.
Promotes cellular uptake of amino acids and
synthesis of proteins.
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Postabsorptive State
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Maintains plasma glucose
concentration.
Plasma [glucagon] increased:
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Stimulates glycogenolysis in the liver
(glucose-6-phosphatase).
Stimulates gluconeogenesis.
Skeletal muscle, heart, liver and kidneys
use fatty acids as major source of fuel
(hormone-sensitive lipase).
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Diabetes Mellitus
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Chronic high plasma [glucose].
2 forms of diabetes mellitus:
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Type I: Insulin dependent diabetes (IDDM)
Type II: non-insulin dependent diabetes
(NIDDM)
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Insulin-dependent Diabetes
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b cells destroyed by autoimmune attack.
Killer T cells target glutamate decarboxylase
in the beta cells.
Glucose cannot enter the adipose cells, rate
of fat synthesis lags behind the rate of
lipolysis.
Ketone production occurs, producing
ketoacidosis.
Increased plasma [glucagon].
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Non-insulin Dependent
Diabetes
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Slow to develop.
Genetic factors are
significant.
Occurs most often in
people who are
overweight.
Decreased sensitivity to
insulin or an insulin
resistance.
 Obesity.
Do not usually develop
ketoacidosis.
High plasma [insulin]
or normal [insulin].
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Hypoglycemia
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Oversecretion of
insulin after a
carbohydrate meal.
Caused by an
exaggerated response
to a rise in blood
glucose.
Occurs in people who
are genetically
predisposed to type II
diabetes.
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Metabolic Regulation
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Anabolic effects of insulin are
antagonized by the hormones of the
adrenals, thyroid and growth hormones.
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Adrenal Medulla
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Metabolic effects similar
to glucagon.
Stimulate glycogenolysis.
Stimulate release of
glucose from the liver.
Stimulate lipolysis and
release of fatty acids.
NE stimulates b3
receptors in brown fat.
Contains uncoupling
protein that dissociates
electron transport from
ATP production.
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Glucocorticoids
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Release stimulated release of ACTH.
Supports the effects of increased
glucagon.
Promotes lipolysis and ketogenesis.
Promotes protein breakdown in the
muscles.
Promotes liver gluconeogenesis.
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Thyroxine
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Active form is T3.
Stimulates cellular respiration by:
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Stimulate active transport Na+/ K+
pumps:
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Production of uncoupling proteins.
Lowers cellular [ATP]
Increases metabolic heat.
Increases metabolic rate.
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Growth Hormone
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Somatotropin.
Inhibited by somatostatin.
Stimulates growth in children and
adolescents.
Stimulated by:
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GHRH.
Increase in plasma [amino acids].
Decrease in plasma [glucose].
Pulsitile, increasing during sleep, decreased
during day.
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Growth Hormone
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IGF-1:
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IGF-2:
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Liver produces and secretes IGF-1 in response to
GH.
Stimulates cell division and growth of cartilage.
Has more insulin-like actions.
Promotes anabolism and catabolism.
Stimulates cellular uptake of amino acids.
Decreases glucose utilization by the tissues.
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Growth Hormone
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Gigantism:
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Acromegaly:
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Excess GH secretion in children.
Excess GH secretion in adults after the epiphyseal
discs are sealed.
Growth of soft tissue.
Dwarfism:
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Inadequate secretion of GH during childhood.
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Regulation of Ca++ and
Phosphate
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Ca++ and phosphate concentrations are affected by:
 Bone formation and resorption.
++ and P0 3 Intestinal absorption of Ca
4
 Urinary excretion.
Osteoblasts:
 Secrete an organic matrix.
Osteoclasts:
 Secrete enzymes to dissolve hydroxyapatite.
Formation and resorption of bone occur constantly at
rates determined by osteoblasts and osteoclasts.
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Parathyroid Hormone
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PTH.
Single most important hormone in the control
of plasma [Ca++].
Stimulated by decreased plasma [Ca++].
 Stimulates osteoclasts to reabsorb bone.
++ from
 Stimulates kidneys to reabsorb Ca
glomerular filtrate, and inhibit reabsorption
of P043-.
 Promotes formation of vitamin D3.
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Vitamin D3
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Directly stimulates intestinal absorption
of Ca++ and P043-.
Directly stimulates bone reabsorption.
Kidney reabsorption of Ca++ and P043-.
Simultaneously raising Ca++ and P043results in increased tendency of these 2
ions to precipitate as hydroxyapatite
crystals.
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Vitamin D3
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Pre-vitamin D3is synthesized in the skin when
exposed to mid-ultraviolet waves.
Pre-vitamin D3 isomerized to vitamin D3
(cholecalciferol).
Cholecalciferol is hydroxylated in liver to form
25 hydroxycholecalciferol.
In proximal convoluted tubule is hydroxylated
to 1,25 dihydroxycholecalciferol (active
vitamin D3).
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Calcitonin
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Works with PTH and vitamin D3 to
regulate plasma [Ca++].
Stimulated by increased plasma [Ca++].
Inhibits the activity of osteoclasts.
Stimulates urinary excretion of Ca++ and
P043- by inhibiting reabsorption.
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Negative Feedback Control
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Secretion of
PTH, vitamin D3,
and calcitonin
influenced by
plasma [Ca++].