Victoria Childs
Chapter 6 Study Questions
Macronutrients
Due 11/11/2013
1. Ingesting large quantities of one amino acid, or one group of amino acids that use the
same carrier system could cause the amino acids to compete for absorption. The amino
acid consumed in the greatest quantity can impair the absorption of other amino acids
using the same carrier system. Because of this, amino acid supplements can result in
imbalanced or impaired amino acid absorption. Peptide absorption is more rapid than
free amino acid absorption. Nitrogen assimilation after consuming protein- containing
foods is superior to nitrogen assimilation following free amino acid consumption. In
other words, expensive supplements that do not taste very good can cause
gastrointestinal distress.
2. In transamination reactions, the amino group of an amino acid is transferred to an αketo acid. The α- keto acid that the amino group is transferred to becomes an amino
acid, and the amino acid that the amino group is transferred from becomes an α-keto
acid. Transamination reactions are important for dispensable amino acid synthesis.
Aminotransferases/transaminases catalyze transamination.
Aminotransferases/transaminases typically require pyridoxal phosphate (PLP), the
coenzyme form of vitamin B6. Tyrosine aminotransferase, alanine aminotransferase
(ALT), branched-chain aminotransferases, and aspartate aminotransferase (AST) are
examples of aminotransferases. ALT and AST are two of the most active
aminotransferases in the body. ALT and AST involve 3 key amino acids and α-keto
acids: alanine and pyruvate, glutamate and α-ketoglutarate, and aspartate and
oxaloacetate. Alanine’s amino groups are transferred to an α-keto acid such as αketoglutarate by ALT, which transfers pyruvate and another amino acid, such as
glutamate. The amino groups from aspartate are transferred to an α-keto acid, such as
α-ketoglutarate by AST forms oxaloacetate and another amino acid, such as glutamate.
Glutamate and α-ketoglutarate readily transfer and/or accept amino groups, which
makes transamination reactions reversible. Amino acids are present in various tissues
in various amounts. The concentration of AST in the heart is greater than the
concentration of AST in the liver, muscle, and other tissues. The concentration of ALT in
the liver is greater than the concentration of of ALT in the heart. The concentration of
ALT in the kidneys is moderate, and the concentrations of ALT in other tissues is small.
Serum concentrations of these enzymes, under normal conditions are low. However,
when injury or damage to an organ occurs, the serum concentrations can rise, meaning
that serum concentrations of these enzymes can be an indicator of damage. In patients
with liver damage, abnormally high AST and ALT concentrations, as well as abnormally
high concentrations of other enzymes, such as lactate dehydrogenase and alkaline
phosphatase are found. In patients with heart damage, such as heart attack patients,
enzymes such as AST, that are found in the heart, will leak out of the heart and into the
blood, raising serum concentrations. The rise in serum concentrations indicates
damage. α-keto acids can be used nutritionally. When kidney failure occurs, nitrogenous
compounds that are excreted in the urine under normal conditions will accumulate in the
blood. Providing kidney failure patients with α-keto acids of some essential amino acids
will allow some of the excess nitrogen to be used to aminate the α-keto acids, which
lowers the concentration of nitrogen in the blood while providing the patient with
essential nutrients. Lysine, histidine, and threonine are three amino acids that cannot
undergo transamination to an appreciable extent, so they cannot be effectively given as
α-keto acids. Deamination reactions only involve removing the amino group from an
amino acid, not transferring the amino group to another compound. Glutamate, glycine,
histidine, serine, and threonine are commonly deaminated amino acids. However, many
commonly deaminated amino acids can also be transaminated. Dehydratases,
dehydrogenases, and lyases are the enzymes that carry out deamination reactions and
produce an α- keto acid and ammonia or an ammonia ion. Threonine is deaminated by
threonine dehydratase to α-ketobutyrate and ammonia. Ammonia is generally converted
to the ammonium ion at the physiological pH of the body, but the conversion is
reversible.
3. The urea cycle is important for removing ammonia and ammonia ions from the body.
The urea cycle occurs in the liver. The urea cycle is composed of 5 steps. Four high
energy bonds are used in the urea cycle. There are two nitrogen atoms in a urea
molecule, one is from ammonia, and the other is from aspartate. The carbon is derived
from CO2/HCO3-. Once the urea molecule is formed, it travels to the kidneys via the
blood, to be excreted in urine. Up to approximately 25% of urea in blood is secreted into
the intestinal lumen, where bacteria can degrade it and yield ammonia. Urea cycle
enzyme activity fluctuates with hormone concentration and diet. In individuals who have
low protein diets or acidosis, urea synthesis diminishes and urinary urea nitrogen
excretion significantly decreases. Substrate availability results in short term changes in
ureagenesis rates. healthy individuals with normal protein intake have blood urea
nitrogen (BUN) concentrations between 8 to 20 mg/dL, and urinary urea nitrogen
composes about 80% of total urinary nitrogen. Glucocorticoids and glucagon promote
amino acid degradation and generally increase mRNA for urea cycle enzymes. Multiple
genetic mutations (defects) have been found in the enzymes involved in the urea cycle.
The defects generally result in hyperammonemia (high blood ammonia levels) and
makes a protein-restricted diet necessary. In patients with advanced liver disease, urea
synthesis is diminished, and blood ammonia concentrations increase. The increased
blood ammonia levels are believed to contribute to hepatic encephalopathy, which is
characterized by coma (brain dysfunction). Decreasing blood ammonia levels is the
medical treatment for encephalopathy. Gastrointestinal tract contents are acidified with
drugs such as lactulose. Gastrointestinal tract contents are acidified to promote
ammonia diffusion out of the blood and into the gastrointestinal tract. Antibiotics are also
prescribed to destroy the intestinal tract bacteria that produce ammonia.
4. Glucogenic amino acids yield pyruvate or intermediates of the TCA cycle through
catabolism. Ketogenic amino acids produce acetyl-CoA or acetoacetate through
catabolism. Acetoacetate and acetyl-CoA are used to form ketone bodies. Some amino
acids can be both glucogenic and ketogenic. Two amino acids that are both glucogenic
and ketogenic are phenylalanine and tyrosine. Phenylalanine and tyrosine can be
degraded to form fumarate, which is a TCA cycle intermediate, as well as to form
acetoacetate. Fumarate can be used to form glucose and acetoacetate, and
acetoacetate can be used to synthesize ketone bodies. Another amino acid that is both
glucogenic and ketogenic is isoleucine. Isoleucine produces both succinyl-CoA and
acetyl-CoA through catabolism. Threonine can be catabolized through multiple
pathways to produce succinyl-CoA or pyruvate through glucogenic pathways and
acetyl-CoA through a ketogenic pathway. Another amino acid that can be either
glucogenic or ketogenic is tryptophan. The only amino acids that are completely
ketogenic are leucine and lysine. A high blood glucagon to insulin ratio and high blood
cortisol concentrations can accelerate the conversation of amino acids glucagon. When
blood glucose levels are low, blood glucagon concentrations are generally elevated.
This may occur in between meals or during periods of fasting, which causes liver
glycogen stores to be depleted. During times of infection, trauma/injury, and certain
diseases (such as liver disease and untreated diabetes mellitus) blood glucagon can be
elevated and possibly also cortisol and/or epinephrine.
5. Albumin, retinol-binding protein and transthyretin are some proteins that have clinical
significance. Albumin is the most abundant transport protein, and it functions by
transporting some nutrients (tryptophan, fatty acids, and vitamin B6), minerals (calcium,
zinc, and small amounts of copper), and some drugs. Albumin is synthesized in the liver
and released into the blood. The rate of albumin synthesis is affected by osmotic
pressure and osmolarity. Healthy individuals make approximately 9 to 12 g of albumin
per day. Albumin is often used to indicate an individual's protein status, especially
visceral protein status. However, due to the fact that albumin has a relatively long halflife, it is not as sensitive a visceral protein status indicator as some other plasma
proteins. Retinol-binding protein and transthyretin (also known as prealbumin) are also
synthesized by the liver. Retinol-binding protein transports retinol and thyroid hormone.
Like albumin, retinol-binding protein and transthyretin are biochemical indicators of
visceral protein status. Retinol-binding protein and transthyretin have relatively shorter
half-lives than albumin, so they are more sensitive visceral protein status change
indicators than albumin. Individuals who have not consumed adequate dietary protein
will have diminishing blood concentrations of albumin, retinol-binding protein, and
prealbumin over time. Plasma concentrations below 3.5 g/dL of albumin below 18 m/dL
of prealbumin, and below 2.1 mg.dL of retinol-binding protein are indicative of
inadequate visceral protein status. These individuals require a high energy, high protein
diet (providing healthy livers) to encourage improvements in visceral protein status.
6. The amino acid pool is approximately 150 g. The amino acid pool includes the amino
acids circulating in the blood as well as the amino acids found within cells. The amino
acids are the products of the digestion and absorption of protein and the breakdown of
endogenous tissues. The amino acid pool is composed of both endogenous and
exogenous amino acids. The amino acids of the amino acid pool mare found in plasma
as well as in the cytosol of body cells. Endogenous amino acid reuse is believed to be
the primary source of the amino acids used in protein synthesis. The amount of amino
acids in the amino acid pool seems to remain relatively constant despite the fact that
protein intake and tissue protein degradation rates vary. The amount of nonessential
amino acids in the pool is greater than the amount of essential amino acids in the pool.
Lysine and threonine are the essential amino acids found in the greatest quantity.
Alanine, aspartate, glutamate, and glutamine are the nonessential amino acids found in
the greatest concentration. As much as 80g of glutamine can be found in the amino acid
pool. In response to various stimuli (such as physiological state and hormones) amino
acids are taken up by tissues and metabolized. Tissues extract amino acids to produce
energy, or synthesize non-essential amino acids, protein, nitrogen-containing nonprotein compounds, biogenic amines, neurotransmitters, neuropeptides, hormones,
glucose, fatty acids, or ketones, depending on the hormonal environment and nutritional
status of the individual. Protein turnover includes both protein synthesis and protein
degradation. Protein synthesis and protein degradation are under individual controls,
however, together they account for approximately 10% to 25% of resting energy
expenditure. Protein synthesis rates can be high, such as with protein accretion during
growth. Protein degradation is predominant during illness. Protein turnover rates vary
among body tissues (visceral protein turnover is more rapid than skeletal muscle protein
turnover). Muscle accounts for 25% to 35% of protein turnover in the body due to its
mass. Protease activity is the primary means of protein degradation. Proteases are
compartmentalized in the cytosol, in lysosomes, or in proteasomes. Lysosome and
proteasome contributions in proteolysis vary depending upon both tissue and
physiological status. Constant protein degradation is important to ensure a flux of amino
acids through the cytosol, which can be used for cell maintenance and/or growth.
7. Tissues and organs use amino acids to synthesize proteins, as well as some
nitrogen-containing compounds. Amino acid metabolism varies in different organs.
Often, the products from amino acid metabolism in one organ are needed in another
organ, which makes the organs dependent upon each other. Since intestinal cells are
the first cells of the body to receive dietary amino acids, organ interdependence begins
with intestinal cells. Ammonia transport is one of many roles of glutamine. Ammonia
produced from amino acid reactions enters the urea cycle. In extrahepatic tissues,
particularly muscle and also the lungs, brain, adipose, and heart, ammonia and
ammonium ion utilization is catalyzed by glutamine synthetase with glutamate in an
ATP-dependent reaction to form glutamine. Each day the body produces approximately
40 to 80 grams of glutamine. Typically in these cells ammonia is generated by amino
acid deamination and deamidation. Ammonia is also formed from AMP deamination in
muscles. In the muscle, ATP degradation generates AMP, which rapidly occurs during
exercise. The transamination of branched-chain amino acids with α-ketoglutarate to
form branched-chain α-keto acids and glutamate, proving that branched-chain amino
acid transamination produces glutamate. Ammonia produced by AMP deamination
produces glutamine when ammonia combines with glutamate. Glutamine formed in
muscle is released into the blood to be used by other tissues. Gastrointestinal system
cells and immune system cells (macrophages, lymphocytes, and monophages) rely on
glutamine catabolism for producing energy. During periods of alkalosis, or in the
absorptive state, glutaminase activity in the liver increases, producing ammonia, which
is used in the urea cycle. In a state of acidosis, glutamine use for the urea cycle
diminishes, and glutamine is released into the blood by the liver to be transported to and
taken up by the kidneys, where it is used in acid-base balance. Glutamine is catabolized
by glutaminase to produce ammonia and glutamate, in renal tubular cells. Glutamate
dehydrogenase can further catabolize glutamate, producing another ammonia as well
as α-ketoglutarate. Alanine is another amino acid that is important in transferring amino
groups produced by amino acid catabolism between tissues. During times of illness,
between meals, in times with a need of excessive glucose, and in times of fasting
characterized by low stores of carbohydrates and a ratio of glucagon to insulin where
there is more glucagon, typically, glutamate will transfer its amino group to pyruvate,
which is produced by glucose oxidation through glycolysis which forms alanine and αketoglutarate. Once the alanine is made, the muscle releases it into the blood so it can
travel to the liver. Once alanine reaches the liver, it is transaminated back to pyruvate,
which can be used to produce glucose. Glutamate produced with transamination may
undergo deamination, which provides ammonia that can be used in urea synthesis. This
is known as the alanine-glucose or glucose-alanine cycle. Glucose produced from
alanine is released into the blood to be transported to and uptaken by muscle. Once
glucose is in muscles, the muscle cells use glucose to produce pyruvate through
glycolysis. The pyruvate can then be transaminated to produce alanine. The alanineglucose cycle transports nitrogen to the liver to be converted to urea, and allows the
regeneration of needed substrates. Levels of glutamine and alanine are elevated
because they are released into the blood by muscles undergoing proteolysis.
8. Limiting amino acid refers to the indispensable amino acid present in the lowest
quantity. Consuming only low-quality proteins can result in certain amino acids being
inadequately available, which could prevent the body from making its own proteins.
Consuming certain proteins together can ensure that all the indispensable proteins are
consumed. This process is known as mutual supplementation. For example, legumes
and grains complement each other. Also, protein digestibility is important for the use of
amino acids. Protein digestibility is measured by the absorbed amounts of amino acids
after ingesting protein. Animal proteins are more digestible than plant proteins. The
digestibility as well as the amino acid content are used to indicate protein quality.
PDCAAS (protein digestibility corrected amino acid score) is used often to indicate
protein quality. PDCAAS must be used to provide food label information for foods
intended to be consumed by individuals 1 year old or older, as well as on foods that
make health claims. PDCAAS is a method that compares the amount of the limited
amino acid in a test protein to the amount of the same amino acid in a reference protein.
Once that value is determined, it is multiplied by the digestibility of the test protein.
Comparing a test protein’s amino acid composition with a reference pattern is an
alternative to PDCAAS. The reference pattern is the amino acid requirements of
children 1 to 3 years old. Since these children are still growing and developing, the
amount of each required amino acid is higher than the amounts adults require.
Choosing this age group allows protein availability evaluation to meet indispensable
amino acid and nitrogen requirements. The scoring pattern is expressed in mg amino
acid per g protein. The scoring pattern is calculated by dividing mg required for
individual amino acids for children by g protein requirement. The amino acid score, also
known as the chemical score involves determining a test protein’s amino acid
composition. This can be done in a laboratory with the use of either high-performance
liquid chromatography techniques or an amino acid analyzer. The indispensable amino
acid content is the only amino acid content of the test protein that is determined. Once
that value is determines, it is compared with that of the reference protein. The lowest
scoring amino acid in relation to the test protein on a percentage scale is the first
limiting amino acid. Comparing the quality of various proteins to the reference is useful
although it may not be as important to protein nutriture as a reference pattern
comparisons for different groups of the population.
9. During times of starvation, protein synthesis decreases. This occurs due to reduced
mRNA necessary for protein translation as well as a decrease in the rate at which
peptide bonds are formed. Proteins that have a very high rate of turnover (plasma
proteins, for example) are synthesized 30% to 40% less than the normal rate, and even
lower in muscle tissue. Protein degradation rates decrease gradually so daily nitrogen
loss is small when an individual is suffering chronic starvation. The daily nitrogen loss in
individuals of normal weight are approximately 4 to 5 grams of urinary nitrogen. Protein
turnover changes with starvation largely result from changes in the concentrations of
hormones. Production of insulin sharply decreases. Adipocytes and muscle become
sort of resistant to the action of insulin. The somewhat resistance to the action of insulin
means that the circulating insulin is not effective in the promotion of the uptake of
cellular nutrition for lipogenesis and protein synthesis. A decrease in insulin activity
combined with an increase in the synthesis of counter regulatory hormones (glucagon
and catecholamines) promotes the mobilization of fatty acids from adipose tissue,
proteolysis, and ketone production. Cortisol promotes muscle protein catabolism to
provide gluconeogenic substrates. The secretion of tri-iodothyronine lowers the
metabolic rate of the body, which lowers energy needs. During the first few days of
starvation or fasting, the amount of glycogen in the liver decreases. During this time
muscles undergo proteolysis. The excretion of urinary 3-methylhistidine increases,
which reflects the catabolism of myofibrillar protein. The muscles that are undergoing
proteolysis release an amino acid mixture into the blood. The amino acid mixture
contains relatively high concentrations of glutamine and alanine. A preferred substrate
for gluconeogenesis is alanine, which also stimulates glucagon secretion, a
gluconeogenic hormone. Alanine released by muscle is uptaken by the liver, where the
nitrogen is removed and converted to urea, which is excreted by the kidney. Pyruvate
can be used to make glucose through gluconeogenesis in the liver. Another way
glucose is produced in the liver is through the Cori cycle, which uses recycled pyruvate
and lactate. Glucose that is produced in the liver can be released into the blood for
cellular metabolism and uptake. Glutamine that muscle releases circulates in the blood
to be uptaken and metabolized mainly by the gastrointestinal tract, and the kidneys over
time. With continued starvation or fasting, fatty acids and glucose continue being used
for energy, but ketones that are produced by fatty acid oxidation in the liver are also
used. Gluconeogenesis and protein catabolism decrease occurs at the same time as
tissue and brain adaptation to using ketones as an energy source. Accelerated ketone
production increases acidosis. When this occurs, a greater amount of glutamine is
directed to the kidneys to maintain the acid-base balance. The amino groups from
glutamine are used for ammonia production in the kidneys. The ammonia is able to
combine with hydrogen ions to be excreted in urine to help minimize acidosis.
Glutamine’s carbon skeleton is used in the kidneys to make glucose through
gluconeogenesis. After fasting for approximately 5-6 weeks, total splanchnic glucose
production is about 80 g per day, 10-11 grams of which are synthesized from ketones,
35 to 40 grams per day are synthesized from recycled pyruvate and lactate, 20 grams
per day are produced from glycerol, and 15 to 20 grams per day are produced from
amino acids, primarily alanine released from muscle. Ketone use decreases needed
glucose to allow lean body mass to spread. Since the body requires less glucose, less
protein has to be broken down in order to provide amino acids for gluconeogenesis.
Amino acids produced from muscle tissue proteolysis are able to be used to synthesize
important visceral proteins. The turnover rates of visceral proteins are more rapid than
those of muscle. In response to trauma/injury, disease, and sepsis, a hypermetabolic,
catabolic state can occur. Basal metabolic rate, or metabolism, is elevated in a
hypermetabolic state. The degree of hypermetabolism depends upon the condition’s
severity. When an individual undergoes minor surgery, or suffers minor injury,
metabolism rises, as well as the catabolic state, which could last less than a week.
Patients who suffer multiple traumatic injuries or major burns may have
hypermetabolism that lasts several months. Metabolic stress, like starvation, results in
body tissue degradation. Adipose tissue will undergo lipolysis during times of metabolic
stress. Unlike starvation, during times of stress, the fatty acids produces through
lipolysis do not generate ketones. Ketones are not produced during times of stress
because insulin inhibits ketogenesis. Body proteins are continually degraded when
ketone use does not occur to supply the body with the amino acids used to synthesize
glucose through gluconeogenesis, as well as crucial acute phase proteins. An increase
in muscle catabolism induced by metabolic stress is combined with a decrease in the
uptake of amino acids, and a decrease in protein synthesis in the muscle. The result is
muscle cachexia, which is characterized by the weakness and wasting of muscles. The
excretion of urinary 3-methylhistidine increases with metabolic stress, which reflects
protein catabolism increase, as well as a daily total of approximately 30 g, or more of
urinary nitrogen, about 30 g of hydrated lean tissue is broken down. Host defense and
wound repair are prioritized during metabolic stress, and body tissues pay the price.
Hormone concentration differences are partially responsible for substrate use
differences. Hormone concentration changes in combination with sepsis, as well as
changes in body temperature, blood pressure, white blood cell count, as well as heart
rate and respiration rate. Change is referred to as SIRS, or systemic inflammatory
response syndrome. When metabolic stress occurs, catecholamines, glucocorticoids
glucagon and insulin release increase. Body tissues become resistant to the action of
insulin, which results in hyperglycemia. Also, with extensive trauma, elevated
concentrations of blood cortisol can occur for prolonged periods of time, and they will
promote ongoing hyperglycemia and proteolysis. During metabolic stress, additional
changes in hormones can occur, which include antidiuretic hormone (ADH) and
aldosterone release. Renal sodium and fluid reabsorption are promoted by aldosterone.
Urination is inhibited by antidiuretic hormone, and blood volume is increased. ADH and
aldosterone aid in diminishing fluid loss, which restores circulation, which can be
depressed as a result of burns, fever, hemorrhage associated with surgery or injury, and
shock. Cytokine release during metabolic stress also differs from that during starvation.
Immune system cells are the main producers of cytokines. Cytokines mediate many
hormone concentration changes (increased cortisol, protein metabolism, changes)
during metabolic stress. Certain proteins are degraded preferentially during the acute
phase response. Proteins that are not preferentially degraded are synthesized. During
metabolic stress, retinol-binding protein, albumin, and prealbumin synthesis decreases.
However, response protein, or acute phase protein synthesis increases. Acute phase
proteins are synthesized by macrophages, lymphocytes, fibroblasts, and the liver. With
inflammation and sepsis, more metallothionein and ferritin are produced in the liver.
Concentrations of hepatic zinc and iron concentrations increase, whereas plasma zinc
and iron concentrations decrease.
Citation
Gropper, S., & Smith, J. (2013). Advanced nutrition and human metabolism. (6th ed.,
pp. 190-247). Belmont, CA: Wadsworth, Cengage Learning.