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DR. PHILLIP SWARTZ A&P II
METABOLISM
Page 144
Nutrients are chemical substances in food that provide energy, form new body
components, or assist in the functioning of various body processes. There are six
principal
classes
of
nutrients
-
carbohydrates,
lipids,
proteins,
minerals,
vitamins, and water. The end products of digestion that ultimately reach body
cells are monosaccharides, amino acids, fatty acids, glycerol, and monoglycerides.
Some are used to synthesize new structural molecules in cells or to synthesize new
regulatory molecules such as hormones and enzymes. Most are used to produce energy
to
sustain life
transport,
DNA
processes. This energy
replication,
synthesis
is used for
of
proteins
processes such as
in
other
active
molecules,
muscle
contraction, and nerve impulse conduction. Until the energy is needed, it is
stored in ATP.
Some minerals and many vitamins are part of enzyme systems that catalyze
reactions undergone by carbohydrates, proteins, and lipids.
Water has five major functions. It is an excellent solvent and suspending medium,
it participates in hydrolysis reactions, it acts as a coolant, it lubricates, and
it helps to maintain a constant body temperature due to its ability to release and
absorb heat slowly.
Metabolism
refers
to
all
the
chemical
reactions
of
the
body.
The
body's
metabolism may be thought of as an energy balancing act between anabolic or
synthetic and catabolic or degradative reactions.
In living cells those chemical reactions that combine simple substances into more
complex
molecules
are
collectively
known
as
anabolism.
An
anabolic
process
requires energy which is supplied by catabolic reactions.
The chemical reactions that break down complex organic compounds into simple ones
are collectively known as catabolism. Catabolic reactions release the available
chemical
energy
in
organic
molecules.
This
energy
is
then
stored
in
ATP.
Catabolic reactions release energy that can be used to drive anabolic reactions.
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Oxidation - Reduction Reactions
Oxidation is the removal of electrons and hydrogen ions (hydrogen atoms) from a
molecule or, less commonly, the addition of oxygen to a molecule. Most oxidations
are actually dehydrogenations, that is, they involve the loss of hydrogen atoms.
An example of an oxidation is the conversion of lactic acid into pyruvic acid.
When a substance is oxidized, the free hydrogen atoms are transferred to another
compound by substances that work with enzymes called coenzymes.
Reduction is the addition of electrons and hydrogen ions or hydrogen atoms to a
molecule or, less commonly, the removal of oxygen from a molecule. Reduction is the
opposite of oxidation. An example of reduction is the conversion of pyruvic acid
into lactic acid. Within a cell oxidation and reduction reactions are always
coupled.
That
simultaneously
is,
whenever
reduced.
oxidation-reduction.
This
a
substance
coupling
Oxidation
is
of
usually
is
oxidized
reactions
an
is
another
simply
energy-producing
is
almost
referred
reaction.
to
as
Cells
take nutrients (energy sources) and degrade them from highly reduced compounds
with many hydrogen atoms to highly oxidized compounds with many oxygen atoms or
multiple bonds.
In
body
cells
enzymes
service
catalysts
that
speed
up
chemical
up
chemical
reactions by increasing the frequency of collision, lowering activation energy,
and properly orienting colliding molecules. A catalyst is a chemical substance
that alters the rate of a chemical reaction without becoming part of the products
of the reaction or being used up. Enzymes speed up chemical reactions without an
increase in temperature or pressure, changes that could seriously disrupt or kill
cells. All enzymes are proteins. Enzymes are extremely efficient as catalysts of
biochemical reactions. Enzymes are very specific in the reactions they catalyze
and the molecules with which they react. Such molecules are called substrates.
Enzymes are also subject to various controls by the cellular machinery. Their
rate of synthesis at any given time is under the control of the cells' genes and
is
influenced
by
various
other
usually end in the suffix - ase.
molecules
in
the
cell.
The
names
of
enzymes
DR. PHILLIP SWARTZ A&P II
METABOLISM
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Some enzymes consist only of proteins. Most enzymes, however, contain a protein
called an apoenzyme that is inactive without a nonprotein component called the
cofactor. Together the apoenzyme and cofactor are an activated holoenzyme, or
whole enzyme. If the cofactor is removed, the apoenzyme will not function. The
cofactor can be a metal ion or a complex organic molecule called a coenzyme.
Iron, magnesium, zinc, and calcium are metal ions that serve as cofactors. Many
coenzymes are derived from vitamins. Three coenzymes commonly used by living
cells to carry hydrogen atoms are nicotinamide, adenine dinucleotide (NAD), and
nicotinamide adenine dinucleotide phosphate (NADP), both of which are derivatives
of the B vitamin niacin, and flavin adenine dinucleotide (FAD), a derivative of
vitamin B2 (riboflavin).
Enzymes lower the activation energy. The surface of the substrate makes contact
with a specific region on the surface of the enzyme molecule known as the active
site. A temporary intermediate compound called an enzyme substrate complex forms.
The substrate molecule is transformed and the transformed substrate molecules now
called the products of the reaction move away from the enzyme molecule. After the
reaction is completed, the products of the reaction move away from the enzyme and
the enzyme is free to attach to another substrate molecule.
Concerning carbohydrate metabolism, glucose is the body's preferred source of
energy and the fate of absorbed glucose depends on the body cells' energy needs.
Before glucose can be used by body cells it must first pass through the plasma
membrane
and
then enter
the
cytoplasm.
The
process
by which
this occurs is
facilitated diffusion and the rate of glucose transport is greatly increased by
insulin. Immediately upon entry into cells, glucose combines with a phosphate
group produced by the breakdown of ATP. This addition of a phosphate group to a
molecule is called phosphorylation.
The oxidation of glucose is also known as cellular respiration. It occurs in
every cell in the body and provides the cells' chief source of energy. The
complete oxidation of glucose to carbon dioxide and water produces large amounts
of energy. It occurs in three successive stages - glycolysis, the Kreb's cycle,
and the electron transport chain.
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The term glycolysis refers to a series of chemical reactions in the cytoplasm of a
cell that convert a six-carbon molecule of glucose into two three-carbon molecules
of pyruvic acid, Under aerobic conditions, the process of the complete oxidation of
glucose continues and pyruvic acid is oxidized to form carbon dioxide and water in
two sets of reactions: the Kreb's cycle and the electron transport chain. This is
known as aerobic respiration. However, before pyruvic acid can enter the Kreb's
cycle, it must be prepared. This process occurs in mitochrondia.
Formation of Acetyl coenzyme A
Each step in the oxidation of glucose requires a different enzyme and often a
coenzyme
as
well.
We
are
interested
in
only
one
coenzyme
at
this
point,
a
substance called Coenzyme A (CoA), which contains a derivative of pantothenic
acid, a B vitamin.
During the transitional step between glycolysis and the Kreb's cycle, pyruvic acid
is prepared for entrance into the cycle. Essentially, pyruvic acid is converted to
a two-carbon compound by the loss of carbon dioxide. The loss of a molecule of CO2
by a substance is called decarboxylation. This two-carbon fragment called an
acetyl group attaches itself to coenzyme A and the whole complex is called acetyl
coenzyme A. This substance is now prepared to enter the Kreb's cycle.
Kreb's Cycle
The Kreb's cycle is also called the citric acid cycle, or the tricarboxyclic acid
cycle (TCA). It is a series of reactions that occur in the matrix of mitochrondia
of cells. Coenzyme A carries an acetyl group to a mitochondrian, detaches itself,
and goes back into the cytoplasm to pick up another fragment. The acetyl group
combines with oxaloacetic acid to form citric acid. From this point the Kreb's
cycle consists mainly of a series of decarboxylation and oxidation-reduction
reactions, each controlled by a different enzyme.
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Each time a molecule of pyruvic acid enters the Kreb's cycle, four molecules of
NADH2 and one molecule of FADH2 are produced by the various oxidation -reduction
reactions. These reduced coenzymes are very important because they now contain the
stored energy originally in glucose and then in pyruvic acid. In the next stage in
the complete oxidation of glucose, the electron transport chain, the energy in th e
coenzymes is transferred to ATP for storage.
Electron Transport Chain
The electron transport chain is a series of oxidation-reduction reactions that
occur on mitochrondial cristae in which the energy in NADH2 and FADH 2 is liberated
and transferred to ATP for storage. In the electron transport chain three types of
carrier molecules are alternately oxidized and reduced and participate in the
generation of ATP:
(1) The coenzyme FAD
(2) A coenzyme called coenzyme Q (ubiquinone)
(3) Cytochromes - red protein pigments that have an iron-containing group capable
of alternating between a reduced form (Fe++) and an oxidized form (Fe+++)
Because of the involvement of cytochromes in the electron transport chain, it is
also known as the cytochrome systen}.
Most of the glucose in the body is catabolized to supply energy. However, some
glucose participates in the number of anabolic reactions. One is the synthesis of
glycogen from many glucose molecules. Another is the manufacture of glucose from
the breakdown products of proteins and lipids.
Glucose Storage (Glycogenesis)
If glucose is not needed immediately for energy, it is combined with many other
molecules of glucose to form a long-chain molecule called glycogen. This process
is called glycogenesis. Glycogen is stored in the liver and in skeletal muscles.
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Glucose Release (Glycogenolysis)
When the body needs energy, the glycogen stored in the liver is broken down into
glucose and released into the blood stream to be transported to cells where it
will be catabolized. The process of converting glycogen back to glucose is called
glycogenolysis. Glycogenolysis usually occurs between meals.
Formation of Glucose from Proteins and Fats (Gluconeogenesis)
When your liver runs low on glycogen it is time to eat. If you do not eat your
body
starts
catabolizing
fats
and
proteins.
Both
fat
molecules
and
protein
molecules may be converted in the liver to glucose. The process by which glucose is
formed from noncarbohydrate sources is called gluconeogenesis. Gluconeogenesis is
stimulated by cortisol, one of the glucorticoid hormones of the adrenal cortex and
thyroxine from the thyroid gland. Cortisol mobilizes proteins from body cells
making them available in the form of amino acids, thus supplying a pool of amino
acids for gluconeogenesis. Thyroxine also mobilizes proteins and may mobilize fats
from fat depots by making glycerol available for gluconeogenesis. Gluconeogenesis
is also stimulated by epinephrine, glucagon, and growth hormone.
Lipids are second to carbohydrates as a source of energy. The major function of
adipose tissue is to store fats until they are needed for energy in other parts of
the
body.
Fat
also
insulates
and
protects.
Fats
stored
in
adipose
tissue
constitute the largest reserve of energy. The body can store much more fat than it
can glycogen. Moreover, the energy yield
of fats is more than twice that of
carbohydrates.
Fatty acids are catabolized differently and the process occurs in the matrix of
mitochrondia.
The
first
step
in
fatty
acid
catabolism
involves
a
series
of
reactions called beta oxidation. Through a series of complex reactions involving
dehydration, hydration, and cleavage, enzymes remove pairs of carbon atoms at a
time from the long chain of carbon atoms comprising a fatty acid. The result of
beta oxidation is a series of two-carbon fragments acetyl coenzyme A (CoA).
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As part of normal fatty acid catabolism, the liver can take acetyl coenzyme A
molecules two at a time and condense them to form a substance called acetoacetic
acid which is converted mostly into B-hydroxybutyric acid and partially into
acetone.
formation
These
is
substances
called
are
collectively
ketogenesis.
They
known
then
as
leave
ketone
the
bodies
liver,
and
their
enter
the
bloodstream, and diffuse into other body cells where they are broken down into
acetyl coenzyme A which enters the Kreb's cycle for oxidation.
Lipid Anabolism (Lipogenesis)
Liver cells can synthesize lipids from glucose or amino acids through a process
called lipogenesis. Lipogenesis occurs when a greater quantity of carbohydrate
enters the body than can be used for energy or stored as glycogen. The excess
carbohydrate is synthesized into fats.
Protein Metabolism
During the process of digestion, proteins are broken down into their constituent
amino acids. The amino acids are then absorbed by the blood capillaries and villi
and transported to the liver via the hepatic portal vein. Amino acids enter body
cells by active transport. A certain amount of protein catabolism occurs in the
body each day, although much of this is only partial catabolism. Before amino
acids can be catabolized, they must first be converted to various substances that
can enter the Kreb's cycle. One such conversion consists of removing the amino
group (NH2) from the amino acid, a process called deamination. The liver cells
then convert the NH2 to amonia (NH3) and finally to urea which is excreted in the
urine.
Protein Anabolism
Protein anabolism involves the formation of peptide bonds between amino acids to
produce new proteins. Protein anabolism or synthesis is carried out on the
ribosomes of almost every cell in the body, directed by the cells' DNA and RNA.
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Regulation of Metabolism
Absorbed nutrients have several alternatives based upon the needs of the body.
They may be oxidized for energy, stored, or converted. Hormones are the primary
regulators of metabolism. However, hormonal control is ineffective without the
proper minerals and vitamins. Minerals are inorganic substances. They may appear
in
combination
with
each
other
or
in
combination
with
organic
compounds.
Minerals constitute about 4% of the total body weight and they are concentrated
most heavily in the skeleton. Minerals known to perform functions essential to
life
include
calcium,
phosphorous,
sodium,
manganese,
cobalt,
copper,
zinc,
selenium, and chromium.
Vitamins
Organic
nutrients
required
in
minute
amounts
to
maintain
growth
and
normal
metabolism are called vitamins. Unlike carbohydrates, fats or proteins, vitamins
do not provide energy or serve as building materials. The essential function of
vitamins is the regulation of physiological processes. Of the vitamins whose
functions
are
known,
most
serve
as
coenzymes.
Most
vitamins
cannot
be
synthesized by the body. They may be ingested in foods or pills. The body can
assemble some vitamins if the raw materials called provitamins are provided. The
term
avitaminosis
refers
to
a
deficiency
of
any
vitamin
in
the
diet.
Hypervitaminosis refers to an excess of one or more vitamins. Hypovitaminosis
refers to a deficiency of one or more vitamins. On the basis of solubility,
vitamins are divided into two principal groups, fat soluble and water soluble.
Heat is a form of energy that can be measured as temperature and expressed in
units called calories. A calorie is the amount of heat energy required to raise
the temperature of one gram of water one degree celsius. Since the calorie is a
small unit and large amounts of energy are stored in foods, the kilocalorie is
used instead. A kilocalorie is equal to 1,000 calories and is defined as the
amount of heat required to raise the temperature of 1,000 grams of water one
degree celsius. The apparatus used to determine the caloric value of foods is
called a calorimeter.
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Most of the heat produced by the body comes from oxidation of the food we eat. The
rate at which this heat is produced, known as the metabolic rate, is also measured
in kilocalories. Among the factors that affect metabolic rate are the following:
exercise, nervous system, hormones, body temperature, ingestion of food, and age.
Since many factors affect metabolic rate, it is measured under standard conditions
designated
to
reduce
or
eliminate
those
factors
as
much
as
possible.
These
conditions of the body are called the basal state and the measurement obtained is
the basal metabolic rate or BMR. The person should not exercise for 30 to 60
minutes before the measurement is taken. The individual must be completely at rest
but awake.
Body heat is produced by the oxidation of foods we eat. This heat must be removed
continuously or body temperature would rise steadily. The principal routes of heat
loss include radiation, conduction, convection, and evaporation.
If the amount of heat production equals the amount of heat loss, you maintain a
constant body temperature near 37 degrees celsius or 98.6 degrees Fahrenheit. Body
temperature is regulated by mechanisms that attempt to keep heat production and
heat loss in balance. A center of control of these mechanisms is found in the
hypothalamus in a group of neurons near the anterior portion referred to as the
preoptic area. Some disorders and clinical terms include:
1.
Fever - an abnormally high body temperature. Any substances of capable of
producing
certain
fever
are
phagocytes,
called
namely
exogenous
monocytes
proteins called endogenous pyrogens.
pyrogens.
and
Exogenous
macrophages
to
pyrogens
cause
synthesize
small
Endogenous pyrogens circulate to the
anterior hypothalamus and induce neurons of the preoptic area to secrete
prostaglandins.
2.
Even when body temperature is climbing higher than normal, say 38.3 degrees
Celsius
or
101
occurs.
This
degrees
condition
temperature is rising.
Fahrenheit,
called
a
the
skin
chill
is
remains
a
cold
definite
and
sign
shivering
that
body
DR. PHILLIP SWARTZ A&P II
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Heat cramps occur as a result of profuse sweating that removes water and
salt from the body.
4.
Heat stroke or sunstroke is brought about when the temperature and relative
humidity are high, making it difficult for the body to lose heat by radiation
or evaporation. As a result, there is a decreased flow of blood to the skin,
perspiration is greatly reduced, and body temperature rises sharply.
5.
Heat
exhaustion
or heat
prostration
-
The
body
temperature
is
generally
normal or a little below normal and the skin is cool and clamy (moist) due to
profuse perspiration.
6.
Obesity is defined as a body weight 10% to 20% above a desirable standard as
a result of an excessive accumulation of fat.
7.
Phenylketonuria (PKU) is a genetic error of metabolism characterized by an
elevation of the amino acid phenylalanine in the blood. It is frequently
associated with mental retardation.
8. Cystic Fibrosis is an inherited disease of the exocrine glands that affects
the pancreas, respiratory passageways, and salivary and sweat glands. It is
the most common lethal genetic disease of Caucasians. 5% of the population
are thought to be genetic carriers. The cause of cystic fibrosis has recently
been linked to an inability of chloride ions to cross epithelial cells in
affected regions of the body. Among the most common signs and symptoms are
pancreatic insufficiency, pulmonary involvement, and cirrhosis of the liver.
It is characterized by the production of thick exocrine secretions that do
not drain easily from the respiratory passageways.
9. Celiac Disease results in malabsorption by the intestinal mucosa due to the
ingestion of gluten. Gluten is the water insoluble protein fraction of wheat,
rye, barley, and oats. In susceptible persons, ingestion of gluten induces
destruction of villi and inhibition of enzyme secretion accompanied by a
variable
amount
of
malabsorption.
The
condition
is
easily
remedied
administering a diet that excludes all cereal grains except rice and corn.
by
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10. Kwashiorkor - Some dietary proteins are referred to as complete proteins,
that
is,
they
contain
adequate
amounts
of
essential
amino
acids.
Sources
of
complete proteins are primary animal products such as milk, meat, fish, poultry,
and eggs. Incomplete proteins lack essential amino -acids. An example is zein, the
protein in corn, which lacks the essential amino acids tryptophan and lysine. The
diet of many African natives consists largely of cornmeal. As a result, many
African children especially develop a protein deficiency called Kwashiorkor. It
is characterized by hypoprotein edema of the abdomen, lethargy, failure to grow,
and
sometimes
mental
retardation.