Transcript No Slide Title

Chapter 25
Metabolism
• Functions of food
– source of energy
– essential nutrients
– stored for future use
• Metabolism is all the chemical reactions of
the body
– some reactions produce the energy stored in
ATP that other reactions consume
– all molecules will eventually be broken down
and recycled or excreted from the body
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Catabolism and Anabolism
• Catabolic reactions breakdown complex
organic compounds
– providing energy (exergonic)
– glycolysis, Krebs cycle and electron transport
• Anabolic reactions synthesize complex
molecules from small molecules
– requiring energy (endergonic)
• Exchange of energy requires use of ATP
(adenosine triphosphate) molecule.
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ATP Molecule & Energy
• Each cell has about 1 billion ATP molecules that last for less than
one minute
• Over half of the energy released from ATP is converted to heat
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Energy Transfer
• Energy is found in the bonds between atoms
• Oxidation is a decrease in the energy
content of a molecule
• Reduction is the increase in the energy
content of a molecule
• Oxidation-reduction reactions are always
coupled within the body
– whenever a substance is oxidized, another is
almost simultaneously reduced.
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Oxidation and Reduction
• Biological oxidation involves the loss of
(electrons) hydrogen atoms
– dehydrogenation reactions require coenzymes
to transfer hydrogen atoms to another
compound
– common coenzymes of living cells that carry H+
• NAD (nicotinamide adenine dinucleotide )
• NADP (nicotinamide adenine dinucleotide
phosphate )
• FAD (flavin adenine dinucleotide )
• Biological reduction is the addition of
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electrons (hydrogen atoms) to a molecule
Mechanisms of ATP Generation
• Phosphorylation is
– bond attaching 3rd phosphate group
contains stored energy
• Mechanisms of phosphorylation
– within animals
• substrate-level phosphorylation in cytosol
• oxidative phosphorylation in mitochondria
– in chlorophyll-containing plants or bacteria
• photophosphorylation.
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Phosphorylation in Animal Cells
• In cytoplasm (1)
• In mitochondria (2, 3 & 4)
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Carbohydrate Metabolism--In Review
• In GI tract
– polysaccharides broken down into simple sugars
– absorption of simple sugars (glucose, fructose &
galactose)
• In liver
– fructose & galactose transformed into glucose
– storage of glycogen (also in muscle)
• In body cells --functions of glucose
– oxidized to produce energy
– conversion into something else
– storage energy as triglyceride in fat
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Fate of Glucose
• ATP production during cell respiration
– uses glucose preferentially
• Converted to one of several amino acids in
many different cells throughout the body
• Glycogenesis
– hundreds of glucose molecules combined to
form glycogen for storage in liver & skeletal
muscles
• Lipogenesis (triglyceride synthesis)
– converted to glycerol & fatty acids within liver &
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Glucose Movement into Cells
• In GI tract and kidney tubules,
Na+/glucose symporters
• Most other cells, GluT facilitated
diffusion transporters move glucose
into cells
– insulin increases number of GluT
transporters in the membrane of most
cells
– in liver & brain, always lots of GluT
transporters
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• Glucose 6-phosphate forms
immediately inside cell (requires
ATP) thus, glucose hidden in cell
• Concentration gradient favorable for
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more glucose to enter
Glucose Catabolism
• Cellular respiration
– 4 steps are involved
– glucose + O2 produces
H2O + energy + CO2
• Anaerobic respiration
– called glycolysis (1)
– formation of acetyl CoA (2)
is transitional step to Krebs cycle
• Aerobic respiration
– Krebs cycle (3) and electron transport chain (4)
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Glycolysis of Glucose & Fate of Pyruvic
Acid
• Breakdown of six-carbon
glucose molecule into 2 threecarbon molecules of pyruvic acid
– 10 step process occurring in cell
cytosol
– produces 4 molecules of ATP after
input of 2 ATP
– utilizes 2 NAD+ molecules as
hydrogen acceptors
• If O2 shortage in a cell
– pyruvic acid is reduced to lactic
acid so that NAD+ will be still
available for further glycolysis
– rapidly diffuses out of cell to blood
– liver cells remove it from blood &
convert it back to pyruvic acid
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10 Steps of Glycolysis
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Formation of Acetyl Coenzyme A
• Pyruvic acid enters the
mitochondria with help of
transporter protein
• Decarboxylation
– pyruvate dehydrogenase converts
3 carbon pyruvic acid to 2 carbon
fragment (CO2 produced)
– pyruvic acid was oxidized so that
NAD+ becomes NADH
• 2 carbon fragment (acetyl
group) is attached to
Coenzyme A to form Acetyl
coenzyme A which enter Krebs
cycle
– coenzyme A is derived from
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pantothenic
acid
(B JWS
vitamin).
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Krebs Cycle (Citric Acid Cycle)
• Series of oxidationreduction &
decarboxylation reactions
occurring in matrix of
mitochondria
• It finishes the same as it
starts (4C)
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– acetyl CoA (2C) enters at
top & combines with a 4C
compound
– 2 decarboxylation reactions
peel 2 carbons off again
when CO2 is formed
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Krebs Cycle
• Energy stored in bonds is released step by step
to form several reduced coenzymes (NADH &
FADH2) that store the energy
• In summary: each Acetyl CoA
molecule that enters the Krebs
cycle produces
– 2 molecules of C02
• one reason O2 is needed
– 3 molecules of NADH + H+
– one molecule of ATP
– one molecule of FADH2
• Remember, each glucose
produced
2 acetyl CoA molecules
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The Electron Transport Chain
• Series of integral membrane
proteins in the inner
mitochondrial membrane
capable of oxidation/reduction
• Each electron carrier is reduced
as it picks up electrons and is
oxidized as it gives up
electrons
• Small amounts of energy
released in small steps
• Energy used to form ATP by
chemiosmosis
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Chemiosmosis
• Small amounts of energy
released as substances are
passed along inner membrane
• Energy used to pump H+ ions
from matrix into space
between inner & outer
membrane
• High concentration of H+ is
maintained outside of inner
membrane
• ATP synthesis occurs as H+
diffuses through a special H+
channel in inner membrane
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Electron Carriers
• Flavin mononucleotide (FMN) is derived
from riboflavin (vitamin B2)
• Cytochromes are proteins with heme group
(iron) existing either in reduced form
(Fe+2) or oxidized form (Fe+3)
• Iron-sulfur centers contain 2 or 4 iron atoms
bound to sulfur within a protein
• Copper (Cu) atoms bound to protein
• Coenzyme Q is nonprotein carrier mobile in
the lipid bilayer of the inner membrane 25-19
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Steps in Electron Transport
• Carriers of electron transport chain are clustered into 3
complexes that each act as proton pump (expel H+)
• Mobile shuttles pass electrons between complexes
• Last complex passes its electrons (2H+) to a half of O2
molecule
to form a water molecule (H2O)
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Proton Motive Force & Chemiosmosis
• Buildup of H+ outside the inner membrane creates + charge
– electrochemical gradient potential energy is called proton motive
force
• ATP synthase enzyme within H+ channel uses proton
motive force to synthesize ATP from ADP and P
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Summary of Cellular Respiration
• Glucose + O2 is broken down into
CO2 + H2O + energy used to form 36
to 38 ATPs
– 2 ATP are formed during glycolysis
– 2 ATP are formed by phosphorylation
during Krebs cycle
– electron transfers in transport chain
generate 32 or 34 ATPs from one glucose
molecule
• Summary in Table 25.1
• Points to remember
– ATP must be transported out of
mitochondria in exchange for ADP
• uses up some of proton motive force
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– Oxygen is required or many of these
steps can not occur
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Carbohydrate Loading
• Long-term athletic events (marathons) can
exhaust glycogen stored in liver and skeletal
muscles
• Eating large amounts of complex
carbohydrates (pasta & potatoes) for 3 days
before a marathon maximizes glycogen
available for ATP production
• Useful for athletic events lasting for more than
an hour
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Glycogenesis & Glycogenolysis
• Glycogenesis
– glucose storage as glycogen
– 4 steps to glycogen
formation in liver or
skeletal muscle
– stimulated by insulin
• Glycogenolysis
– glucose release not a simple
reversal of steps
– enzyme phosphorylase splits off a glucose molecule by
phosphorylation to form glucose 1-phosphate
– enzyme only in hepatocytes so muscle can’t release glucose
– enzyme activated by glucagon (pancreas) & epinephrine (adrenal)
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Gluconeogenesis
• Liver glycogen runs low if fasting, starving or not eating
carbohydrates forcing formation from other substances
– lactic acid, glycerol & certain amino acids (60% of available)
• Stimulated by cortisol (adrenal) & glucagon (pancreas)
– cortisol stimulates breakdown of proteins freeing amino acids
– thyroid mobilizes triglycerides from adipose tissue
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Transport of Lipids by Lipoproteins
• Most lipids are nonpolar and must be combined with
protein to be tranported in blood
• Lipoproteins are spheres containing hundreds of
molecules
– outer shell polar proteins
(apoproteins) & phospholipids
– inner core of triglyceride &
cholesterol esters
• Lipoprotein categorized by
function & density
• 4 major classes of lipoproteins
– chylomicrons, very low-density, low-density & high-density
lipoproteins
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Classes of Lipoproteins
• Chylomicrons (2 % protein)
– form in intestinal epithelial cells to transport dietary fat
• apo C-2 activates enzyme that releases the fatty acids from the
chylomicron for absorption by adipose & muscle cells
• liver processes what is left
• VLDLs (10% protein)
– transport triglycerides formed in liver to fat cells
• LDLs (25% protein) --- “bad cholesterol”
– carry 75% of blood cholesterol to body cells
– apo B100 is docking protein for receptor-mediated endocytosis
of the LDL into a body cell
• if cells have insufficient receptors, remains in blood and more likely to
deposit cholesterol in artery walls (plaque)
• HDLs (40% protein) --- “good cholesterol”
– carry cholesterol from cells to liver for elimination
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Blood Cholesterol
• Sources of cholesterol in the body
– food (eggs, dairy, organ meats, meat)
– synthesized by the liver
• All fatty foods still raise blood cholesterol
– liver uses them to create cholesterol
– stimulate reuptake of cholesterol containing bile normally lost in
the feces
• Desirable readings for adults
– total cholesterol under 200 mg/dL; triglycerides 10-190 mg/dL
– LDL under 130 mg/dL; HDL over 40 mg/dL
– cholesterol/HDL ratio above 4 is undesirable risk
• Raising HDL & lowering cholesterol can be accomplished
by exercise, diet & drugs
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Fate of Lipids
• Oxidized to produce ATP
• Excess stored in adipose tissue or liver
• Synthesize structural or important
molecules
– phospholipids of plasma membranes
– lipoproteins that transport cholesterol
– thromboplastin for blood clotting
– myelin sheaths to speed up nerve conduction
– cholesterol used to synthesize bile salts and
steroid hormones.
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Triglyceride Storage
• Adipose tissue removes triglycerides from
chylomicrons and VLDL and stores it
– 50% subcutaneous, 12% near kidneys, 15% in
omenta, 15% in genital area, 8% between
muscles
• Fats in adipose tissue are ever-changing
– released, transported & deposited in other
adipose
• Triglycerides store more easily than
glycogen
– do not exert osmotic pressure on cell
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Lipid Catabolism: Lipolysis &
Glycerol
• Triglycerides are split into fatty acids & glycerol by
lipase
– glycerol
• if cell ATP levels are high, converted into glucose
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enters
Lipolysis & Fatty acids
Liver cells
• Beta oxidation in mitochondria removes 2 carbon units from fatty
acid & forms acetyl coenzyme A
• Liver cells form acetoacetic acid from 2 carbon units & ketone
bodies from acetoacetic acid (ketogenesis)
– heart muscle & kidney cortex prefer to use acetoacetic acid for ATP
production
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Lipid Anabolism: Lipogenesis
• Synthesis of lipids by liver cells = lipogenesis
– from amino acids
• converted to acetyl CoA & then to triglycerides
– from glucose
• from glyceraldehyde 3-phosphate to triglycerides
• Stimulated by insulin when eat excess calories
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Ketosis
• Blood ketone levels are usually very low
– many tissues use ketone for ATP production
• Fasting, starving or high fat meal with few
carbohydrates results in excessive beta oxidation
& ketone production
– acidosis (ketoacidosis) is abnormally low blood pH
– sweet smell of ketone body acetone on breath
– occurs in diabetic since triglycerides are used for ATP
production instead of glucose & insulin inhibits
lipolysis
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Fate of Proteins
• Proteins are broken down into amino acids
– transported to the liver
• Usage
– oxidized to produce ATP
– used to synthesize new proteins
• enzymes, hemoglobin, antibodies, hormones,
fibrinogen, actin, myosin, collagen, elastin & keratin
– excess converted into glucose or triglycerides
• no storage is possible
• Absorption into body cells is stimulated by
insulinlike growth factors (IGFs) & insulin
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Protein Catabolism
• Breakdown of protein into
amino acids
• Liver cells convert amino
acids into substances that
can enter the Krebs cycle
– deamination removes the
amino group (NH2)
• converts it to ammonia (NH3)
& then urea
• urea excreted in the urine
• Converted substances enter
the Krebs cycle to produce
ATP
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Protein Anabolism
• Production of new proteins by formation of peptide bonds
between amino acids
– 10 essential amino acids are ones we must eat because we can
not synthesize them
– nonessential amino acids can be synthesized by transamination
(transfer of an amino group to a substance to create an amino
acid)
• Occurs on ribosomes in almost every cell
• Stimulated by insulinlike growth factor, thyroid hormone,
insulin, estrogen & testosterone
• Large amounts of protein in the diet do not cause the
growth of muscle, only weight-bearing exercise
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Phenylketonuria (PKU)
• Genetic error of protein metabolism that
produces elevated blood levels of amino acid
phenylalanine
– causes vomiting, seizures & mental retardation
– normally converted by an enzyme into tyrosine which
can enter the krebs cycle
• Screening of newborns prevents retardation
– spend their life with a diet restricting phenylalanine
– restrict Nutrasweet which contains phenylalanine
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Key Molecules at Metabolic Crossroads
• Glucose 6-phosphate,
pyruvic acid and acetyl
coenzyme A play
pivotal roles in
metabolism
• Different reactions
occur because of
nutritional status or
level of physical activity
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Role of Glucose 6-Phosphate
• Glucose is converted to glucose 6phosphate just after entering the cell
• Possible fates of glucose 6-phosphate
– used to synthesize glycogen when glucose is
abundant
– if glucose 6-phosphatase is present, glucose
can be re-released from the cell
– precursor of a five-carbon sugar used to
make RNA & DNA
– converted to pyruvic acid during glycolysis in
most cells of the body
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Role of Pyruvic Acid
• 3-carbon molecule formed when glucose
undergoes glycolysis
• If oxygen is available, cellular respiration
proceeds
• If oxygen is not available, only anaerobic
reactions can occur
– pyruvic acid is changed to lactic acid
• Conversions
– amino acid alanine produced from pyruvic acid
– to oxaloacetic acid of Krebs cycle
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Role of Acetyl coenzyme A
• Can be used to synthesize fatty acids,
ketone bodies, or cholesterol
• Can not be converted to pyruvic acid so
can not be used to reform glucose
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Metabolic Adaptations
• Absorptive state
– nutrients entering the bloodstream
– glucose readily available for ATP production
– 4 hours for absorption of each meal so
absorptive state lasts for 12 hours/day
• Postabsorptive state
– absorption of nutrients from GI tract is
complete
– body must meet its needs without outside
nutrients
• late morning, late afternoon & most of the evening
• assuming no snacks, lasts about 12 hours/day
more9/ecells
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Metabolism during Absorptive State
• Body cells use glucose for ATP production
– about 50% of absorbed glucose
• Storage of excess fuels occur in
hepatocytes, adipocytes & skeletal muscle
– most glucose entering liver cells is converted to
glycogen (10%) or triglycerides (40%)
– dietary lipids are stored in adipose tissue
– amino acids are deaminated to enter Krebs
cycle or are converted to glucose or fatty acids
– amino acids not taken up by hepatocytes used
by other cells for synthesis of proteins
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Absorptive State
Points where
insulin
stimulation
occurs.
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Regulation of Metabolism during
Absorptive State
• Beta cells of pancreas release insulin
• Insulin’s functions
– increases anabolism & synthesis of storage
molecules
– decreases catabolic or breakdown reactions
– promotes entry of glucose & amino acids into cells
– stimulates phosphorylation of glucose
– enhances synthesis of triglycerides
– stimulates protein synthesis along with thyroid &
growth hormone
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Metabolism During Postabsorptive
State
• Maintaining normal blood glucose level (70 to
110 mg/100 ml of blood) is major challenge
– glucose enters blood from 3 major sources
• glycogen breakdown in liver produces glucose
• glycerol from adipose converted by liver into glucose
• gluconeogenesis using amino acids produces glucose
– alternative fuel sources are
• fatty acids from fat tissue fed into Krebs as acetyl CoA
• lactic acid produced anaerobically during exercise
• oxidation of ketone bodies by heart & kidney
• Most body tissue switch to utilizing fatty
acids, except brain still need glucose. 25-47
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Postabsorptive State
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Regulation of Metabolism
During Postabsorptive State
• As blood glucose level declines,
pancreatic alpha cells release glucagon
– glucagon stimulates gluconeogenesis &
glycogenolysis within the liver
• Hypothalamus detects low blood sugar
– sympathetic neurons release
norepinephrine and adrenal medulla
releases norepinephrine & epinephrine
• stimulates glycogen breakdown & lipolysis
• raises glucose & free fatty acid blood levels
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Metabolism During Fasting & Starvation
• Fasting means going without food for hours/days
• Starvation means weeks or months
– can survive 2 months or more if drink enough water
– amount of adipose tissue is determining factor
• Nutritional needs
– nervous tissue & RBC need glucose so amino acids
will be broken down for gluconeogenesis
• blood glucose stabilizes at 65 mg/100 mL
• lipolysis releases glycerol used in gluconeogenesis
– increase in formation of ketone bodies by liver cells
due to catabolism of fatty acids
• by 40 days, ketones supply 2/3’s of brains fuel for ATP
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Absorption of Alcohol
• Absorption begins in the stomach but is
absorbed more quickly in the small intestine
– fat rich foods keep the alcohol from leaving the
stomach and prevent a rapid rise in blood alcohol
– a gastric mucosa enzyme breaks down some of the
alcohol to acetaldehyde
• Females develop higher blood alcohols
– have a smaller blood volume
– have less gastric alcohol dehydrogenase activity
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Metabolic Rate
• Rate at which metabolic reactions use
energy
– energy used to produce heat or ATP
• Basal Metabolic Rate (BMR)
– measurements made under specific conditions
• quiet, resting and fasting condition
• Basal Temperature maintained at 98.6
degrees
– shell temperature is usually 1 to 6 degrees lower
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Heat Production
• Factors that affect metabolic rate and thus the
production of body heat
– exercise increases metabolic rate as much as 15 times
– hormones regulate basal metabolic rate
• thyroid, insulin, growth hormone & testosterone increase
BMR
– sympathetic nervous system’s release of epinephrine
& norepinephrine increases BMR
– higher body temperature raises BMR
– ingestion of food raises BMR 10-20%
– children’s BMR is double that of an elderly person
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Mechanisms of Heat Transfer
• Temperature homeostasis requires mechanisms
of transferring heat from the body to the
environment
– conduction is heat exchange requiring direct contact
with an object
– convection is heat transfer by movement of gas or
liquid over body
– radiation is transfer of heat in form of infrared rays
from body
– evaporation is heat loss due to conversion of liquid
to a vapor (insensible water loss)
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Hypothalamic Thermostat
• Preoptic area in anterior hypothalamus
– receives impulses from thermoreceptors
– generates impulses at a higher frequency when
blood temperature increases
– impulses propagate to other parts of hypothalamus
• heat-losing center
• heat-promoting center
• Set in motion responses that either lower or
raise body temperature
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Thermoregulation
• Declining body temperature
– thermoreceptors signal
hypothalamus to produce TRH
– TRH causes anterior pituitary to
produce TSH resulting in
• vasoconstriction in skin
• adrenal medulla stimulates cell
metabolic rate
• shivering
• release of more thyroid hormone
raises BMR
• Increases in body temperature
– sweating & vasodilation
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Hypothermia
• Lowering of core body temperature to 35°C
(95°F)
• Causes
– immersion in icy water (cold stress)
– metabolic diseases (hypoglycemia, adrenal
insufficiency or hypothyroidism)
– drugs (alcohol, antidepressants, or sedatives)
– burns and malnutrition
• Symptoms that occur as body temperature
drops
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Regulation of Food Intake
• Hypothalamus regulates food intake
– feeding (hunger) center
– satiety center
• Stimuli that decrease appetite
– glucagon, cholecystokinin, epinephrine, glucose &
leptin
– stretching of the stomach and duodenum
• Signals that increase appetite
– growth releasing hormone, opioids,
glucocorticoids, insulin, progesterone &
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somatostatin
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Guidelines for Healthy Eating
• Nutrients include water, carbohydrates,
lipids, proteins, vitamins and minerals
• Caloric intake
– women 1600 Calories/day is needed
– active women and most men 2200 Calories
– teenage boys and active men 2800
calories
• Food guide pyramid developed by U.S.
Department of Agriculture
– indicates number of servings of each food25-59
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Food Guide Pyramid
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Minerals
• Inorganic substances = 4% body weight
• Functions
– calcium & phosphorus form part of the matrix of
bone
– help regulate enzymatic reactions
• calcium, iron, magnesium & manganese
– magnesium is catalyst for conversion of ADP to
ATP
– form buffer systems
– regulate osmosis of water
– generation of nerve impulses
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Vitamins
• Organic nutrients needed in very small
amounts
– serve as coenzymes
• Most cannot be synthesized by the body
• Fat-soluble vitamins
– absorbed with dietary fats by the small intestine
– stored in liver and include vitamins A, D, E, and K
• Water-soluble vitamins are absorbed along
with water in the Gl tract
– body does not store---excess excreted in urine
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– includes the B vitamins and vitamin C
Antioxidant Vitamins
• C, E and beta-carotene (a provitamin)
• Inactivate oxygen free radicals
– highly reactive particles that carry an unpaired
electron
• damage cell membranes, DNA, and contribute to
atherosclerotic plaques
• arise naturally or from environmental hazards such
as tobacco or radiation
• Protect against cancer, aging, cataract
formation, and atherosclerotic plaque
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Vitamin and Mineral Supplements
• Eat a balanced diet rather than taking
supplements
• Exceptions
– iron for women with heavy menstrual
bleeding
– iron & calcium for pregnant or nursing
women
– folic acid if trying to become pregnant
• reduce risk of fetal neural tube defects
– calcium for all adults
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Fever
• Abnormally high body temperature
– toxins from bacterial or viral infection =
pyrogens
– heart attacks or tumors
– tissue destruction by x-rays, surgery, or trauma
– reactions to vaccines
• Beneficial in fighting infection & increasing
rate of tissue repair during the course of a
disease
• Complications--dehydration, acidosis, &
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Obesity
• Body weight more than 20% above
desirable standard
• Risk factor in many diseases
– cardiovascular disease, hypertension,
pulmonary disease,
– non-insulin dependent diabetes mellitus
– arthritis, certain cancers (breast, uterus,
and colon),
– varicose veins, and gallbladder disease.
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