1. Sarah Allaben
Protein Metabolism
Protein Digestion
An understanding of protein metabolism must first begin with the concepts of basic protein
digestion. When dietary protein is consumed, the first scene of digestion is that of the stomach, with the
denaturing of the protein folds. The first step in denaturing protein is the release of the gastric zymogen
pepsinogen by the chief cells of the stomach. When pepsinogen meets the hydrochloric acid (HCl) of the
stomach, a chemical reaction ensues that cleaves pepsinogen into pepsin, which is the active form
needed for protein degradation.25 Like all enzymes, pepsin is an amino acid-derived enzyme, making it a
protein susceptible to denaturation,20 however, its durable structure allows it to avoid being denatured by
the acidic HCl of the stomach, unlike the dietary proteins being consumed.
After initial degradation by pepsin, protein digestion continues into the lumen of the small
intestine, where further enzymes such as trypsin and chymotrypsin, continue to breakdown the dietary
protein molecules into smaller peptides (chains of amino acids). These peptides are then exposed to the
brush border enzyme carboxypeptidase, which works to break these smaller molecules down to the
individual amino acid components.16 Once the amino acids are freed from the peptide, they are absorbed
by amino acid transporters lining the small intestine, where they travel through the portal hepatic system
and make their way to the liver. The liver plays many important roles in protein metabolism and
turnover and is vital to the homeostasis of the protein in the body.
Protein Turnover
Proteins are constantly in a fight for a balance in the body between protein synthesis and protein
degradation. If synthesis is outweighing degradation, then the body is in an anabolic state, which occurs
during normal lean tissue growth and development. If protein degradation is outweighing synthesis, then
the body is experiencing a catabolic state, which can be seen in illness, stress, trauma, muscle repair, or
dietary deficiencies.16
Normal daily protein turnover in humans tends to average 300g to 400g, whereas protein intake
from dietary sources averages 50g to 80g per day.18 It is also important to note that the contribution of
whole-body protein turnover to basic bodily metabolism represents about 20% in adults, though is
higher during periods of growth in youth or during repair.18 Amino acids, derived from dietary protein or
synthesized by the body, act as the building blocks for all protein synthesis in the body, making an
adequate and diverse consumption of the 20 amino acids vitally important to basic bodily functions. The
body prioritizes amino acid usage based on perceived immediate needs. General protein compounds
made in cells include antibodies, enzymes, hormones, structural components that give support to cells,
and transport or storage proteins.20,24 The synthesis of these proteins is regulated by many factors,
including interactions among hormonal, nutritional, neural, and inflammatory influences, among
others.24 If dietary protein consumption is inadequate, the body will obtain amino acids needed for the
synthesis of these proteins at the expense of lean tissue. Specifically, amino acids needed for
physiological needs can be obtained from three sources: 1) amino acids released during digestion and
absorption, 2) tissue protein breakdown during normal protein turnover, and 3) De novo synthesis,
which is the synthesis of complex molecules from simple molecules, such as the synthesis of one amino
acid or new protein from the byproducts of amino acid breakdown (termed deamination).20
One specific area of protein turnover and deficiency is with regards to low-protein diets, which
can sometimes be seen with a vegetarian or vegan lifestyle. A review by Phili et al. examines concerns
that arise with an improperly followed vegetarian lifestyle including, but not limited to, overall protein
deficiency, anemia, decreased muscle mass, and menstrual disruption, especially with increased physical
activity.14 According to the American Family Physician, the prevalence of anemia (specifically iron-
deficiency anemia) is as follows: 2% in adult men, 9% to 12% in adult non-Hispanic white woman, and
almost 20% in African-American and Mexican-American women.8 The risk of additional anemias, such

2. as megaloblastic, microcytic, and pernicious, can all increase with the adaptation of a vegetarian/vegan
lifestyle. Phili et al. reasoned that if these diets are properly followed (i.e. adequate consumption of non-
animal based protein sources), these anemias and additional consequences of low-animal based protein
diets can be avoided, and that a vegetarian or vegan diet can be highly protective against cardiovascular
disease, obesity, DM2, and can improve physical fitness. Ensuring successful protein balance of not only
a vegetarian/vegan lifestyle, but of an average Western diet is rooted in a main concept: sufficient pools
of free amino acids in the body.
Before the specific utilization of amino acids by other tissues can be discussed, amino acid
“storage” must be presented. The body is unable to store proteins or amino acids in the same sense that
carbohydrates and lipid are stored, i.e. glycogen and adipose tissue. The distribution of each amino acid
is maintained as a free amino acid in solution in blood and inside the cells.16 These pools serve as the
reservoirs for amino acid transport and utilization throughout the body.
As mentioned previously, after digested amino acids pass through the alimentary tract, they are
absorbed by the lumen of the small intestine and transported into portal blood. This introduces the
concept of the free amino acid pools. Before other tissues utilize amino acids, they are freely circulating
in these amino acid pools. Overall, a wide range of concentrations is found among amino acids across
the various free pools that exist. While the concentrations of individual amino acids vary among
different free pools, there is a relatively constant abundance of amino acids throughout the body. There
are two main points to keep in mind regarding the abundance of amino acids in the free pools of
extracellular and intracellular compartments: 1) amino acid concentrations vary widely among amino
acids, and 2) free amino acids are generally concentrated inside cells.16 This second concept is important
for the process of protein synthesis as described later.
Transport in Liver: Transamination & Deamination
As amino acids are circulating in their free amino acid pools, they make a vital stop at the liver
via portal hepatic circulation. The stop of amino acids in the liver is a highly important one for these
protein metabolites. The liver has many important functions, one of which is acting as the predominant
site for transamination and deamination. Transamination and deamination occur in all living tissues, but
predominately in the liver, and both are necessary processes to manage excess protein intake, as well as
to synthesize new keto-based, gluco-based, and amino acid based compounds.13
Before discussing the fates of free amino acids in the liver, the actual transport mechanisms of
amino acids through the lipid membranes must be discussed. The transport of amino acids between the
intra- and extracellular pools involves gradients and active/passive transport systems across cell
membranes. Transport occurs both in and out of cells and the actual cell transporters fall into two
categories: those that are sodium-dependent channels and those are sodium-independent channels.16
Many different transporters exist for different types and groups of amino acids and each has their own
unique gradient threshold. For example, the essential amino acids have lower intra- and extracellular
gradients than do the non-essential amino acids, due to their indispensible use in the body. According to
Brosnan (2003), there is no single means of regulating the flux of amino acids. There are varied
mechanisms such as substrate supply, enzyme activity, transporter activity and competitive inhibition
that all play a role in amino acid transport.4
Schlisselberg et al. gives further insight into amino acid transportation when describing that the
long N-terminal tails – the nitrogen end of the protein polypeptide - act as a sensor of the internal pool of
amino acids. The researchers examined a human pathogen Leishmania, which naturally expresses the
proline/alanine transporter. Their findings conclude that the N-terminus of polypeptides indeed plays a
strong role in amino acid transporter specificity17, which gives further insight to the regulatory processes
surrounding amino acid transportation.
Once inside the liver cell, the first step in catabolizing amino acids is the removal of the amine
group (-NH3), which can be transferred through transamination or removed altogether through

3. deamination. Transamination is used to synthesize new, non-essential amino acids and involves the
transfer of an amine group (-NH3) from an amino acid onto a keto acid, which creates a new amino acid
and keto acid.16 It is understood that essential amino acids cannot by synthesized by the body and
therefore must be supplied by the diet. However, the liver can synthesize the other non-essential amino
acids that are still equally important for basic bodily functions. The liver uses amino acids that are in the
free amino acid pools to create these non-essential amino acids in response to the body’s specific
demands. For example, the liver can utilize transamination to synthesize the essential amino acid
tyrosine from free phenylalanine, and the essential amino acid cysteine from free methionine.13
When the amino acids undergo oxidative deamination in the liver, the byproducts of this
breakdown include the amine group (-NH3), one hydrogen atom, and the carbon skeleton.13 The bonding
of the now free hydrogen atom with the amine group is a normal process during deamination, though
creates the unfavorable and toxic compound, ammonia (NH4). This compound does not arise during
transamination because the amine group is transferred onto a keto acid, thus creating a new amino acid
and a new glucose substrate or keto acid.
Liver’s Role: Urea Cycle
Due to the toxicity of ammonia, accumulation is not a beneficial option for the body. It is
therefore the job of the liver to either utilize ammonia as the α-amino group during amination (described
in detail shortly) or to combine CO2 with ammonia to create urea, a nontoxic substance that is then
safely excreted through the urine by the kidneys.
In a healthy individual, the urea cycle occurs at a fairly constant rate in tune with the amount of
ammonia being produced during deamination. However, the liver can adapt the urea cycle to the needs
of those who are acutely or chronically ill, undergoing trauma or stress, or suffering from a multitude of
other conditions. This concept was seen in a study by Okun et al. where the researchers analyzed the
molecular regulation of the urea cycle in patients with Addison’s Disease (AD) (n = 10) as compared to
healthy controls (n = 10). AD arises from damage to the adrenal cortex, resulting in lower levels of
hormone production, especially glucocorticoid hormones that are responsible for blood sugar
maintenance, as well as immune and stress responses.1 The researchers of this study discuss how
glucocorticoid treatment in AD patients results in lean tissue wasting, which indicates a prominent role
in systemic amino acid metabolism.12 Blood amino acid profiling was conducted and the researchers
found that with this increase loss of lean muscle comes increased urea cycle liver function to keep up
with increased nitrogen circulation derived from heightened protein breakdown in AD patients.12
Though the study included a small sample size, the results give further support to the important role of
the liver in maintaining acceptable NH4 levels to avoid toxic accumulation, especially when considering
the liver’s adaptation to various disease states.12
Liver’s Role: Fate of the Carbon Skeleton
While liver takes care of the amine group through the urea cycle and amino acid synthesis, the
remaining carbon skeleton can undergo various catabolic processes. It can go on to create carbohydrates
or lipid products via the Krebs cycle.2 If the carbon skeleton is derived from one of the 11 glucogenic
amino acids, then the skeleton must undergo a chemical reaction in the liver to convert it to pyruvate,
which is an acceptable gluconeogenic precursor to enter the Krebs cycle for carbohydrate synthesis.2 If
the carbon skeleton is that of one of the two exclusively ketogenic amino acids (either leucine or lysine),
then the skeleton is degraded to acetyl-CoA or acetoacetate, which will also enter the Krebs cycle to be
catabolized for energy or converted to ketone bodies or fatty acids.2 Interestingly, there is a group of five
amino acids that can function as both glucogenic and ketogenic: phenylalanine, isoleucine, tryptophan,
tyrosine, and threonine. The body will utilize these five amino acids for either glucose or fatty acid
precursors depending on the needs of the body.

4. In certain disease states, the Krebs cycle will utilize the different glucogenic and ketogenic
amino acids differently. A highly utilized example is that of Type 2 Diabetes Mellitus. Drábková et al.
aimed to find differences in amino acids and their respective metabolism in patients with DM2 (n = 50).
The researchers found a negative correlation between levels of glutamine, threonine, and histidine
(glucogenic amino acids, specifically) as well as between methionine, threonine, and histidine in patients
with DM2.6 These findings were reported as being in accordance with past data that suggests that the
body of patients with DM2 metabolizes and utilizes various amino acids differently during periods of
fasting. This study showed significant differences (p<0.001) between the metabolism of the above
mentioned amino acids, which supports the statement that the altered levels of amino acids could be a
suitable predictor of the future onset of diabetes.6
Liver’s Role: Plasma Protein Synthesis
Apart from breaking down amino acids and performing the urea cycle, the liver also acts as a site
for new protein synthesis, including synthesis of plasma proteins such as albumin, fibrinogens, and
apolipoproteins. These are produced by the liver and secreted into the blood for circulation.22 In the
eukaryotic cell, the foundation for the synthesis of plasma proteins comes from DNA housed inside the
nucleus of the cells. This DNA is copied into messenger RNA (mRNA), which acts as the blueprints for
protein synthesis, and is excreted into the cytoplasm via nuclear transport pores.23 The mRNA then
attaches to one of many ribosomes lining the endoplasmic reticulum (ER), which initiates the reading of
the instructions. Based on these mRNA instructions, appropriate amino acids are combined to form
polypeptides, a process that continues inside the ER. These polypeptides will ultimately create the final
protein product that is ready for circulation.23 The final step of protein synthesis is inside the Golgi
complex, where the polypeptide chain is finalized and then transported in a transporter vesicle to the
cellular membrane (exocytosis), where it is excreted into the serum and can function as a completed
protein.23 Protein synthesis is a normal and highly occurring process in the liver and needs sufficient of
each amino acid to successfully produce the many types of proteins in a healthy individual.
Protein Metabolism in Fasting/Starvation
Much of what has been discussed thus far considers protein metabolism in healthy individuals
during the well-fed or postprandial state, apart from specific disease states mentioned. However,
metabolism does not follow such straight forwards guidelines during special cases of fasting and/or
starvation. Protein metabolism shifts in cases of early fasting, refeeding, and prolonged starvation.
In the early fasting state, both muscle and liver use fatty acids as fuel when the blood-glucose
level drops. When blood-glucose (BG) levels drop, there is the release of glucagon from the alpha cells
of the pancreas to initiate gluconeogenesis for BG maintenance. Glucagon targets the liver (mainly) and
the muscle, and calls upon glycogen stores to be utilized for energy.11 From the muscle, lactate and
alanine are shuttled to the liver to be used as substrates in the gluconeogenic pathway. Glucagon
stimulates the glucose-synthesis pathways in the liver by triggering cyclic AMP cascades, which also
work to activate the protein kinases that mediate all known actions of glucagon.11 As the liver depletes
its glycogen stores, gluconeogenesis from lactate and alanine continues, but this process merely replaces
glucose that had already been converted into lactate and alanine by the peripheral tissues. As more
glucose is needed, another source of carbons is required. This brings in glycerol, which is released from
adipose tissue through lipolysis to provide some of the carbon, with the remaining carbons coming from
the hydrolysis of muscle proteins.11 If energy comes soon from dietary sources, then normal cycles of
fed and fasting will continue. However, in cases of starvation or severely limited food intake, this fasting
state continues on.
In a starving state, the body’s first priority is providing energy to the brain and it does this in the
form of glucose. For this reason, and due to the quick utilization of carbohydrates by the body, true
carbohydrate stores can only supply the body with energy for approximately one day, while ketones and

5. lean skeletal muscle can supply the body with some energy for 1 to 3 months, depending on what dietary
consumption (if any) is occurring.11 Because fatty acids cannot be synthesized into glucose, and the
body’s function will be compromised if lean muscle is depleted for energy, the second priority becomes
maintaining lean skeletal muscle and using ketone bodies for energy. The body’s metabolism will
undergo heightened lipolysis to mobilize fatty acids and produce ketone bodies, which can sustain
general brain and body function for several weeks.11 After this time period, when triglycerol stores are
depleted, the body has no choice but to resort to muscle protein for energy. This eventually comes at the
expense of heart, liver, and kidney function, which will ultimately result in death.
The above case assumes that the body has severely limited access to sufficient dietary sources of
energy. However, we know that in many cases, these types of “starvation” may be secondary to disease
states and that clinicians have the means to replenish these fuels. An example of this is seen in research
done by De theije et al. As mentioned earlier, the balance between protein synthesis and degradation
determines the basic for the overall skeletal muscle mass. In cases of Chronic Obstructive Pulmonary
Disease (COPD), muscle atrophy and weight loss are common due to increased energy expenditure to
maintain the O2/CO2 balance in the body.5 Hypoxia, especially with end-stage COPD, is associated
with decreased appetite and malnutrition. The researchers of this study evaluated hypoxic events in mice
(n = 72) and evaluated the metabolic effects of protein synthesis. Overall, hypoxia was seen to increase
protein turnover and protein signaling, which induced the expression of genes involved in proteasomal
and lysosomal protein degradation.5 Decreased regulatory signals for protein synthesis occurred,
resulting in rapid lean muscle wasting in these mice, suggesting the adequate dietary protein intake is
vital to the preservation of lean muscle in both acute and chronically ill COPD patients.5 While proper
energy intake of macro- and micronutrients is important in the ill population, specialized feeding
strategies need to be addressed, as refeeding those who are wasting is a specialized process.
Refeeding syndrome is well understood, though serious issue in the starving population and care
needs to be taken with those are in need of increased calories after a period of caloric deficiency,
especially those suffering from Protein-Energy Malnutrition (PEM). Refeeding syndrome is a high risk
for patients initiating nutrition support or introducing increased amounts of food into the body, and
occurs with an influx of macro- and micronutrients in the GI tract after a period of limited calorie
intake.10 The ingestion of a high amount of these solutes causes a shift in the metabolic balance of the
body, resulting in hypophosphatemia (trademark symptom), hypomagnesaemia, hyponatremia,
hypokalemia, and thiamine deficiency as well as changes in glucose, protein, and fat metabolism.10
A review by Mehanna et al. explains that no randomized controlled trials of treatment have been
published, although there are guidelines that use the best available evidence for managing the
condition.10 Unfortunately, refeeding syndrome still occurs in the hospital setting, and a classic example
is refeeding syndrome in patients with anorexia nervosa (AN). An examination of clinical data by
Kameoka et al. for female AN patients undergoing enteral nutrition support (EN) (n = 99) uncovered
that the average length of poorly controlled phosphate levels was 4.8 ± 3.7 days after admission.9 The
researchers concluded that due to the sensitivity of refeeding syndrome, serum phosphate levels need to
be monitored for more than five days after admission and concurrent administration of oral support.9
With regards to nutrition support and refeeding strategies, evidence and research has shown us
that effective refeeding strategies for those highly malnourished individuals should start with 50% of the
recommended daily protein and energy needs, and should be built up over the first 24 – 48 hours to meet
full needs.3 Protein supplementation should include a diverse blend of amino acids, as different amino
acids play specialized role in disease protecting as is evaluated below.
Amino Acid Highlights: Leucine & Glutamine
A particular utilization of free amino acids is that of glutamic acid and L-glutamine in the
biosynthesis of other certain amino acids in the liver. Glutamic acid, which is derived from the
amination of α-ketoglutarate by ammonia (NH4), can be used in the amination of other α-keto acids to

6. form the corresponding amino acid.15 It can also be converted to L-glutamine, which is considered the
second most important metabolite of ammonia, following urea. L-glutamine plays a highly important
role in both the storage and the transport of ammonia in the blood serum and also assists with the
transamination of additional α-keto acids. It is also the primary substrate for energy in the small
intestine, making the dietary intake and biochemical synthesis of L-glutamine especially vital for proper
bodily function.15 L-glutamine is found highly in bone broth, beef, Chinese cabbage, cottage cheese,
asparagus, and wild caught fish including tuna, cod, and salmon.
An experimental study by Solbu et al. found that there is actually an increase of glutamine
transportation in kidney tubules during chronic metabolic acidosis.19 Metabolic acidosis is understood to
be a serious and potentially fatal condition. To compensate for the increased blood acidity during this
condition, plasma levels of glutamine are increased, thus increasing glutamine metabolism in the kidney
tubules.19 This degradation of glutamine results in the formation of ammonia as mentioned earlier, as
well as bicarbonate (HCO3) ions. These are excreted in the urine, which counteracts acidosis and
restores normal pH of the blood.19 The researchers of this study evaluated the SN1 transporter (a
glutamine transporter of the kidney cells) to assess how it adjusts to shifts in glutamine metabolism
during metabolic acidosis. Their findings correlated with their initial hypothesis that the SN1 transporter
can actually shift and reposition in response to increased glutamine levels, thus increasing the efficiency
of glutamine metabolism in response to metabolic acidosis.19 Their evidence gives further support to the
fact that a high protein diet containing clinically beneficial amino acids during periods of clinical
periods stress, such as metabolic acidosis, aids in resolving the condition.
An additional amino acid of interest is leucine. Leucine is one of the three branched-chain amino
acids (BCAAs), the other two being valine and isoleucine. The BCAAs are known to play a key role in
human metabolism and are used frequently in intensive care, especially concerning liver diseases such
as cirrhosis.21 Leucine plays a central role in muscle tissue metabolism and acts as a foundational
building block for the synthesis of many proteins.21 Because of the strong role of leucine in muscle
protein synthesis, increasing amounts of leucine supplements are being marketed to exercise and muscle
conscious consumers.
A study by Gil et al. evaluated this concept regarding leucine supplementation solely on
increased muscle mass. The researchers explain that leucine, specifically with regards to muscle
contractions, functions as a source of nitrogen for alanine and glutamine to be used in muscle
contraction protein synthesis.7 When examining the effects of increased leucine dosage (27 g
leucine/day) on skeletal muscle hypertrophy of rat subjects (n = 42), the researchers interestingly found
that increased leucine dosage alone did not contribute to increased muscle mass, but rather a
combination of amino acids was needed along with leucine to show any muscle hypertrophy. The amino
acids noted to increase muscle mass in combination with one another were isoleucine, valine, glutamate,
aspartate, asparagine, and leucine.7 While it is understood that leucine is considered as the most
remarkable amino acid related to the synthesis of muscle contractile protein, the researchers conclude
that they could not support the notion that leucine administration combined with exercise training may
have an additive effect for increasing muscle mass. This is an interesting notion for those individuals
that are hoping to increase their muscle mass through leucine supplementation.7
Conclusion
Overall, it can be seen that protein metabolism is a complex, multi-faceted process that is vital
for the normal function of many bodily operations. Adequate and diverse dietary intake of protein
sources is necessary to main proper supplies of the free amino acid pools and to not compromise normal
bodily functions that proteins play vital roles in. Disease states can change the normal pathways of
protein metabolism, making proper protein prescriptions and administrations in the clinical setting vital
to optimal patient recovery. The various research described gives insight to recent evidence surround
protein metabolism in different situations, and research is only expected to grow in this area.

7. References:
1. Addison’s Disease. U.S National Library of Medicine Web site.
https://www.nlm.nih.gov/medlineplus/ency/article/000378.htm. Accessed November 22,
2015
2. Amino Acid Catabolism: Carbon Skeleton. Molecular Biology Web site.
https://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb2/part1/aacarbon.htm Accessed
November 18, 2015
3. Berg JM, Tymoczko JL, Stryer L. Food intake and starvation induced metabolic changes. In
Biochemistry. 5th edition. New York: 2002
4. Brosnan JT. Interorgan amino acid transport and its regulation. J Nutr. 2003;133(6 Suppl
1):2068S-2072S.
5. De theije CC, Langen RC, Lamers WH, Schols AM, Köhler SE. Distinct responses of protein
turnover regulatory pathways in hypoxia- and semistarvation-induced muscle atrophy.
Am J Physiol Lung Cell Mol Physiol. 2013;305(1):L82-
91.http://ajplung.physiology.org/content/305/1/L82
6. Drábková P, Šanderová J, Kovařík J, Kanďár R. An Assay of Selected Serum Amino Acids
in Patients with Type 2 Diabetes Mellitus. Adv Clin Exp Med. 2015;24(3):447-51.
http://www.advances.am.wroc.pl/pdf/2015/24/3/447.pdf
7. Gil JH, Kim CK. Effects of different doses of leucine ingestion following eight weeks of
resistance exercise on protein synthesis and hypertrophy of skeletal muscle in rats. J
Exerc Nutrition Biochem. 2015;19(1):31-8.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4424444/
8. Iron Deficiency Anemia. American Family Physician Web site.
http://www.aafp.org/afp/2007/0301/p671.html. Accessed November 19, 2015
9. Kameoka N, Iga JI, Tamaru M, et al. Risk factors for refeeding hypophosphatemia in
Japanese inpatients with anorexia nervosa. Int J Eat Disord. 2015
10. Mehanna HM, Moledina J, Travis J. Refeeding syndrome: what it is, and how to prevent and
treat it. BMJ. 2008;336(7659):1495-8.
11. Nutrition Support for Adults: Oral Nutrition Support, Enteral Tube Feeding and Parenteral
Tube Feeding. NCBI Web site. http://www.ncbi.nlm.nih.gov/NBK492/ Accessed
November 23, 2015
12. Okun JG, Conway S, Schmidt KV, et al. Molecular regulation of urea cycle function by the
liver glucocorticoid receptor. Mol Metab. 2015;4(10):732-40. http://www-ncbi-nlm-nih-
gov.libweb.ben.edu/pmc/articles/PMC4588454/
13. Oxidation Deamination Reaction. Virtual Chembook Web site.
http://chemistry.elmhurst.edu/vchembook/632oxdeam.html. Accessed November 18,
2015
14. Pilis W, Stec K, Zych M, Pilis A. Health benefits and risk associated with adopting a
vegetarian diet. Rocz Panstw Zakl Hig. 2014;65(1):9-14.
15. Rhoades, Rodney. Bell, David R. The physiology of the liver. In: Medical Physiology:
Principles for Clinical Medicine. Lippincott Williams & Wilkins, 2009

8. 16. Ross Catharine, PhD. Modern Nutrition in Health and Disease. Philadelphia, PA; Lippincott,
Williams & Wilkins; 2014
17. Schlisselberg D, Mazarib E, Inbar E, Rentsch D, Myler PJ, Zilberstein D. Size does matter:
18 amino acids at the N-terminal tip of an amino acid transporter in Leishmania
determine substrate specificity. Sci Rep. 2015;5:16289.
18. Schutz Y. Protein turnover, ureagenesis and gluconeogenesis. Int J Vitam Nutr Res.
2011;81(2-3):101-7. http://www.ncbi.nlm.nih.gov/pubmed/22139560
19. Solbu TT, Boulland JL, Zahid W, et al. Induction and targeting of the glutamine
transporter SN1 to the basolateral membranes of cortical kidney tubule cells during
chronic metabolic acidosis suggest a role in pH regulation. J Am Soc Nephrol.
2005;16(4):869-77.
20. Structural View of Biology. Protein Data Bank Web site.
http://www.rcsb.org/pdb/101/structural_view_of_biology.do?c=Enzymes&sc=Ribozyme
s_-_Enzymes_Made_of_RNA Accessed November 15, 2015
21. The BCAAs. Amino Acid Studies Web site. http://aminoacidstudies.org/bcaa/. Accessed
November 17, 2015
22. The Liver Proteasomes. The Human Protein Atlas Web site.
http://www.proteinatlas.org/humanproteome/liver#livergeneelevated. Accessed
November 19, 2015
23. The Protein Pathway. Pearson Custom Web site.
http://wps.pearsoncustom.com/wps/media/objects/3014/3087289/Web_Tutorials/04_A02
.html. Accessed November 19, 2015
24. What Are Proteins and What do they do? Genetics Home Reference Web site.
http://ghr.nlm.nih.gov/handbook/howgeneswork/protein. Accessed November 17, 2015
25. Zymogens. Washington State Education Department Web site.
http://courses.washington.edu/conj/bess/zymogens/zymogens.html Accessed November
15, 2015