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Review Article Metabolic and Physiological Roles of Branched-Chain Amino Acids



Branch chain amino acids (BCAAs) have unique properties with diverse physiological and metabolic roles. They have functions other than simple nutrition. Different diseases including metabolic disease lead to protein loss, especially muscle protein. Supplementation of BCAAs promotes protein synthesis and reduces break down, as well as improving disease conditions. They are important regulators of mTOR signaling pathway and regulate protein synthesis as well as protein turnover. BCAAs facilitate glucose uptake by liver and SK muscle and also enhance glycogen synthesis. Oxidation of BCAAs seems to be beneficial for metabolic health as their catabolism increases fatty acid oxidation and reduces risk of obesity. BCAAs are also important in immunity, brain function, and other physiological aspects of well-being. All three BCAAs are absolutely required for lymphocyte growth and proliferation. They are also important for proper immune cell function. BCAAs may influence brain protein synthesis, and production of energy and may influence synthesis of different neurotransmitters. BCAAs can be used therapeutically and future studies may be directed to investigating the diverse effects of BCAAs in different tissues and their signaling pathways.
Review Article
Metabolic and Physiological Roles of
Branched-Chain Amino Acids
Md. Monirujjaman1and Afroza Ferdouse2
1Human Nutritional Sciences, University of Manitoba, Winnipeg, MB, Canada R3E 0M2
Correspondence should be addressed to Md. Monirujjaman;
Received 6 July 2014; Accepted 8 August 2014; Published 19 August 2014
Academic Editor: Haile Yancy
Copyright © 2014 Md. Monirujjaman and A. Ferdouse. is is an open access article distributed under the Creative Commons
Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
properly cited.
Branch chain amino acids (BCAAs) have unique properties with diverse physiological and metabolic roles. ey have functions
other than simple nutrition. Dierent diseases including metabolic disease lead to protein loss, especially muscle protein.
Supplementation of BCAAs promotes protein synthesis and reduces break down, as well as improving disease conditions. ey are
important regulators ofmTOR signaling pathway and regulate protein synthesis as well as protein turnover. BCAAs facilitate glucose
uptake by liver and SK muscle and also enhance glycogen synthesis. Oxidation of BCAAs seems to be benecial for metabolic health
as their catabolism increases fatty acid oxidation and reduces risk of obesity. BCAAs are also important in immunity, brain function,
and other physiological aspects of well-being. All three BCAAs are absolutely required for lymphocyte growth and proliferation.
ey are also important for proper immune cell function. BCAAs may inuence brain protein synthesis, and production of energy
and may inuence synthesis of dierent neurotransmitters. BCAAs can be used therapeutically and future studies may be directed
to investigating the diverse eects of BCAAs in dierent tissues and their signaling pathways.
1. Introduction
Amino acids (AAs) are biologically important compounds
containing carboxylic and amine moiety as functional groups
and are the building blocks of protein. ey play important
metabolic and physiological roles in all living organisms.
Although more than 300 AAs have been found, only 20
chain specic to each AA [1]. ree branch chain amino
acids (BCAAs), including isoleucine, leucine, and valine, have
unique properties with diverse physiological and metabolic
roles. BCAAs are primarily oxidized in the peripheral tissue,
in particular in skeletal (SK) muscle, whereas the other AA
catabolizes in the liver. BCAAs may regulate rate of protein
synthesis and degradation in SK muscle and other organs.
BCAAs and aromatic AA bind to the same carrier proteins to
be transported to brain. ey compete with each other and
their ratio in brain may inuence the synthesis of specic
neurotransmitters, and that may inuence the behavior of an
organism [2,3]. BCAAs have glycogen sparing action and
they have an opposite relation with tryptophan levels of brain,
which is the precursor of serotonin. Serotonin is a mediator
of central fatigue. us supplementation of BCAAs may
prevent fatigue during extensive exercise, and diet enriched
with BCAAs may improve muscle protein metabolism, body
maintenance, and also aerobic exercise [3,4]. BCAAs have
functions other than simple nutrition. AAs supplementation
enriched with BCAAs clinically is used for patients with liver
diseases, renal failure, sepsis, and surgical injury [2,57]. It is
also found that BCAAs may aect gene expression, hepato-
cyte apoptosis and regeneration, and insulin resistance. ey
are necessary for lymphocyte proliferation and dendritic cell
maturation, and they also inhibit cancer cell proliferation
metabolic and physiological roles of BCAAs.
2. Metabolism and Metabolic Roles of BCAAs
For metabolism, AAs are needed to be transported into
the cell. Like glucose, AAs are also transported to the
cell via special carrier mediated pathway. Inside the cell,
Hindawi Publishing Corporation
Advances in Molecular Biology
Volume 2014, Article ID 364976, 6 pages
2Advances in Molecular Biology
transamination reaction of BCAAs gives rise to keto acids,
specic to each AA. e keto acids further undergo oxidative
decarboxylation to produce acyl-CoA derivatives and enter
TCA cycle. e enzyme (activity) responsible for BCAA
metabolism is found mostly in SK muscle, heart, and kidney
but to lesser extent in liver [2].
In muscle, BCAAs not only provide nonspecic carbon
source of oxidation for production of energy but also act
as a precursor for muscle protein synthesis. BCAAs are
more energy ecient than glucose. For example, complete
oxidation of leucine in muscle produces more energy than
complete oxidation of glucose in the form of ATP. Oxidation
of BCAAs increases under various physiological conditions
to meet the energy demand including the demand at star-
vation. It is also observed that BCAAs regulate the turnover
of protein in muscles by inhibiting protein degradation and
enhancing protein synthesis [1416]. Several metabolic and
clinical conditions, such as starvation, surgery, trauma, sepsis,
liver disease, and cancer, lead to protein loss especially muscle
protein and supplementation of BCAAs promotes protein
synthesis and reduces break down as well as improving those
conditions [2,1722]. ere is an increasing demand for AAs,
alanine, and glutamine in those clinical conditions and they
can be synthesized in SK muscle from BCAAs oxidation.
So, BCAAs can cover the elevated demands for alanine and
glutamine by the body during those clinical conditions [23].
2.1. Protein Synthesis and Turnover. Initiation of mRNA
translation is one of the key steps in protein synthesis.
Amino acids may stimulate protein synthesis by enhancing
this important step of protein synthesis [24]. Deacylated
tRNA reduces or inhibits protein synthesis by aecting the
initiation step. BCAAs may lead to formation of aminoacyl-
tRNA derivatives that enhance initiation of protein synthesis
by minimizing that inhibitory eect. Another possible way
that BCAAs may inuence protein synthesis is the formation
of active metabolic intermediate by the oxidation of BCAAs
as in turnover. Buse et al. [26]studiedinvitroeectof
BCAAs on protein synthesis by analyzing polysome struc-
tures. Healthy rats were injected with BCAAs intravenously
aer 48–96 hours of fasting. And they observed that the
number of polysomes (units) decreases during fasting state
and supplementation of BCAAs or leucine alone signicantly
increases the density of polysomes, which was not observed
when rat was fed normal food, which suggests that BCAAs,
in particular leucine, enhances protein synthesis. In another
study, Li and Jeerson [25] examined inuence of BCAAs
supplementation on protein turnover in rat SK muscle. Fast-
ing young rats were supplemented with dierent combina-
tions of BCAAs by perfusion. A signicant increase (25–50%)
of muscle protein synthesis and signicant decrease (30%) in
protein degradation were observed in perfused supplemented
group compared to control. It was also observed that when
the BCAAs were removed from complete mixture of amino
acids, the rest of the amino acids showed no eects on protein
turnover [25]. So, BCAAs not only enhance protein synthesis,
but also inuence protein turnover.
2.2. BCAAs and Signaling. Hypoalbuminemia and muscle
wasting symptoms are quite common in liver cirrhotic
patient. Oral administration of BCAA is found benecial by
increasing plasma albumin and reducing muscle wasting in
both animals and humans. It is proposed that BCAAs acceler-
ate protein synthesis in liver and other tissues via mammalian
target of rapamycin (mTOR) signaling pathways. mTOR
is a serine/threonine protein kinase and its signaling path-
ways may regulate protein synthesis and transcription as
well as other cellular functions [27,28]. BCAA, particularly
leucine, is the potent activator of mTOR signaling and
activates protein synthesis by translational initiation [26]. In
astudy[29], rat hepatocytes in culture were incubated with
dierent combinations of BCAAs and secretion of albumin
was observed. It was found that mixture of BCAAs promotes
albumin production in dose dependent manner and they
were the key eectors. Rapamycin, which is the potent
of albumin promoted by leucine. It was also observed that
activation of downstream translational eector proteins of
mTOR, elF4E-BP1, and p70 S6 kinase is induced by leucine
only. And rapamycin completely inhibits those proteins.
ese observations suggest that synthesis of albumin in rat
hepatocytes via mTOR signaling is promoted by BCAAs,
particularly by leucine. In another study [30]starvingmale
rats were orally administered either saline or each BCAA
separately. Also, starved rats were injected intravenously with
only leucine stimulated signicant protein synthesis in SK
muscle compared to controls. Moreover, leucine eectively
enhanced phosphorylation and activation of elF4E-BP1 and
p70 S6 kinase. Both in leucine-treated and starved rats,
rapamycin inhibited protein synthesis.
All of these studies suggest that BCAAs, particularly,
leucine, promote protein synthesis in SK muscle as well as in
2.3. Glucose Metabolism. Cirrhotic patients also suer from
impaired glucose metabolism and many of them develop
diabetes mellitus. Synthesis of glycogen takes place in liver
and SK muscles; they are the main reservoir of glycogen too.
is glycogen store is very important in controlling blood
glucose level. Cirrhotic patients have low level of glycogen
store in their liver and SK muscle compared to healthy
individuals [31]. BCAAs facilitate glucose uptake by liver and
SK muscle as well as enhancing glycogen synthesis. Nishitani
et al. [32] collected soleus muscles from healthy rats and incu-
bated them with leucine in insulin-free conditions to test the
eect of leucine on glucose uptake. ey found that leucine
promotes glucose uptake; moreover, 𝛼-ketoisocaproic acid,
a metabolic product of leucine, showed similar stimulatory
eect. ey observed that inhibition of phosphatidylinositol
3-kinase (PI3-kinase) or protein kinase C (PKC) by selective
inhibitors leads to complete loss of stimulatory eect of
leucine. However, rapamycin treatment showed no eect.
ese observations indicate that leucine stimulates glucose
transport in SK muscle by insulin-independent manner
through PKC and PI3-kinase pathways rather than mTOR
pathway. In another study Peyrollier et al. [33] deprived
Advances in Molecular Biology 3
myoblast L6 cells 1hforAAsandaerthatincubatedthem
with leucine. ey observed a signicant increase of PI3-
kinase and p70 S6 kinase activity. ey also found that glyco-
gen synthase kinase-3 (GSK-3) is inactivated by leucine. GSK-
and stops glycogen synthesis. ese results suggest that
BCAA supplementation may enhance glycogen synthesis by
activating GS.
2.4. Energy Metabolism. ere is an inverse relationship
between physical activity and obesity. Obesity on the other
hand is associated with dierent types of complications,
including metabolic diseases. Regular physical activities keep
a person t with reducing risks of those diseases. It is
benecial and important for us to know how the energy
metabolism is regulated and coordinated. BCAAs oxidation
seems to be benecial for our metabolic health as their
catabolism increases fatty acid oxidation as well as reducing
in obese animals and humans; on the other hand, lower levels
and humans. It is also found that supplementation of BCAAs
enriched protein is benecial in animals and humans by
increasing exercise performance, composition of body pro-
tein and properties, and better glucose tolerance and control;
all of these are related to better health and tness [4].
Nishimura et al. [34] fed mice with high fat diet and sup-
plemented isoleucine to test the eect of isoleucine supple-
mentation on obesity condition, glucose, and fat homeostasis.
ey observed that isoleucine supplementation leads to a
decrease in weight gain and reduced lipid mass in isoleucine
supplemental group compared to control. Triglyceride con-
centrations and degree of hyperinsulinemia were also lower
in hepatic and SK muscle of isoleucine supplemented group.
In a double-blind, placebo-control, cross-over study [35],
human volunteers were supplemented with either the BCAA
oxidation were measured. It was found that BCAA supple-
mentation increases lipid oxidation during exercise and helps
to overcome fatigue condition. e glucose metabolism of
the volunteer also improved. Qin et al. [36]showedthat
there is an inverse relation between BCAA intake and obesity.
Apparent middle aged healthy adults from China, Japan, UK,
and USA, who consumed higher amount of BCAAs, had
low incidence of obesity and overweight status. All of these
evidences suggest that BCAAs have large inuence on energy
metabolism as well as reducing risks of obesity.
3. Physiological Roles of BCAAs
3.1. BCAAs in Immunity. e immune system is important in
protecting host from pathogens (including bacteria, viruses,
fungi, parasites, etc.), existing in surrounding environments,
and also protects from other notorious threats. Immune cells
(i.e., lymphocytes, neutrophils, etc.) express dehydrogenase
and decarboxylase enzyme and can eectively oxidize BCAAs
[3739]. All three BCAAs are absolutely required for lympho-
cytes growth and proliferation. BCAAs are also important for
cytotoxic T lymphocyte and natural killer cell activity [40].
In a study [41] mice were supplemented with diet containing
optimal level of protein or diet containing individual AA,
except for limited amount of BCAAs. e susceptibility
to Salmonella typhimurium infection and immune activity
were measured. ey found a higher mortality rate to S.
typhimurium when mice were fed diet containing restricted
amount of BCAAs (any). e liver and spleen were also
colonizedwithhighernumberofS. typhimurium in that
group of mice. BCAA restriction also leads to lower number
of spleen cells and less antibody titer against S. typhimurium
in the serum. ese results suggest that restriction of any
BCAA may impair host defense system. Human study [42]
with surgery patients shows that higher BCAA supplementa-
tion leads to higher postsurgery blood lymphocytes, higher
immune parameters, and better recovery. Bassit et al. [43]
supplemented BCAAs to male elite triathletes to measure
the eects of that supplementation on immunity parameters.
ey observed that BCAAs supplementation increased lym-
phocyte proliferation and modied the pattern of cytokine
production and shi of the immune response from 2 to
1, which is benecial for the athletes.
3.2. BCAAs in Sepsis. Sepsis is a physiological condition
in which severe inammation occurs in whole body due
to infection and it may be life threatening [44]. Potential
benecial roles of BCAAs in sepsis have been studied. Mori
et al. [5] supplemented total parenteral nutrition (TPN)
enriched with branched-chain amino acids (BCAAs) to
septic rats. ey found that BCAA-enriched TPN leads to
signicant improvement of nitrogen balance and decreases
mortality compared to conventional TPN in septic rats. In
a randomized, multicenter study [45] sepsis patients were
supplemented TPN, enriched with BCAAs or conventional
TPN only. ere was signicant decrease in mortality and
improvements of visceral proteins half-life were observed in
the BCAA-supplemental group. ese studies suggest that
BCAAs have a benecial eect in septic patients.
3.3. BCAAs and Diabetes. Diabetes is one of the most
prevalent diseases worldwide and is associated with several
factors such as age, race, body weight, and food habit. ere is
a strong correlation between circulating BCAAs and diabetes
prediction [46]. In a recent study it was found that patients
with type 2 diabetes, who had impaired fasting glucose,
also had elevated levels of BCAAs compared to healthy
individuals [47]. Mammalian target of rapamycin complex
1 (mTORC1) is a nutrient-sensitive kinase, important for
growth and proliferation of beta cell as well as insulin secre-
tion. BCAAs are important regulators of mTORC1 signaling
and elevated levels of plasma BCAAs for a longer period can
cause hyperactivation of mTOR signaling. And that may lead
to early beta cell dysfunction and destruction [48]. So, it is
important to maintain normal plasma levels of BCAA.
3.4. BCAAs in Brain Functions. BCAAs may also play impor-
tant roles in brain function. BCAAs may inuence brain pro-
tein synthesis and production of energy and may inuence
synthesis of dierent neurotransmitters, that is, serotonin,
4Advances in Molecular Biology
dopamine, norepinephrine, and so forth, directly or indi-
rectly. Major portion of dietary BCAAs is not metabolized by
liver and comes into systemic circulation aer a meal. BCAAs
and aromatic AA, such as tryptophan (Trp), tyrosine (Tyr),
and phenylalanine (Phe), share the same transporter protein
to transport into brain. Trp is the precursor of neurotransmit-
ter serotonin; Tyr and Phe are precursors of catecholamines
(dopamine, norepinephrine, and epinephrine). When plasma
concentration of BCAAs increases, the brain absorption of
BCAAs also increases with subsequent reduction of aromatic
of these related neurotransmitters [3]. Catecholamines are
important in lowering blood pressure. When hypertensive
rats were injected with Tyr, their blood pressure dropped
markedly and injection with equimolar amount of valine
blocks that action [49]. In vigorous working persons, such as
in athletes, depletion of muscle and plasma BCAAs is normal.
And that depletion of muscle and plasma BCAAs may lead
to increase in Trp uptake by brain and release of serotonin.
Serotonin on the other hand leads to central fatigue. So,
supplementation of BCAAs to vigorously working person
may be benecial for their performance and body mainte-
nance [3].
4. Conclusions
BCAAs have unique characteristics as they are not primarily
oxidized in liver and they regulate protein synthesis and
degradation in muscle as well as other tissues. In addition,
BCAAs compete with aromatic AA to enter into brain. ey
have diverse metabolic and physiological roles. BCAAs are
also important regulators of mTOR signaling that regulates
protein and glycogen metabolism in liver and SK muscles.
ese eects in liver and SK muscles are important in
maintaining body composition and glucose balance. ey are
also important regulators of neurotransmitters in brain. So,
BCAAs may be therapeutically useable in various neurologi-
cal disorders. However, more research is needed in this eld.
In vitro and in vivo studies of BCAAs suggest that they might
have benecial eects in various disorders. It is important and
necessary to explore whether BCAAs have other therapeutic
eects on other tissues. Future investigations may be directed
to fully understand the diverse eects of BCAA in dierent
tissues and associated signaling pathways.
Conflict of Interests
e authors declare that there is no conict of interests
regarding the publication of this paper.
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... C3 and C5 species (Koves et al., 2008) and specifically, valine catabolism results in C3-acylcarnitine production (Newgard, 2012). The oxidation of branched-chain amino acids produces more energy than complete oxidation of glucose in the form of ATP (Monirujjaman and Ferdouse, 2014). The low RFI cows at the mid lactation stage may maintain a comparative energy efficiency by catabolizing amino acids for energy source and subsequently diluting amino acid concentration in milk. ...
... In addition, the concentration of pyruvic acid was increased in the high RFI group compared to the low RFI cows suggesting lower uptake of pyruvate by mitochondria to be oxidized to acetylCoA as the energy source may have shifted to amino acid catabolism. Branched chain amino acids (BCAA) such as valine are oxidized in peripheral tissue (Monirujjaman and Ferdouse, 2014) and the catabolism of the BCAA in the mammary gland increases significantly during lactation (Manjarin et al., 2014). The proportion of mammary intracellular valine utilized for metabolism other than protein synthesis was 34% and this proportion appeared to remain unaffected by dietary AA regime, indicating that valine may participate considerably in metabolism. ...
... In the current study, the concentration of valine in milk from high RFI cows markedly exceeds the concentration in the low RFI groups (12.0 ± 2.8 vs. 3.4 ± 0.8) indicating that low RFI cows obtain more energy by catabolism of valine. The oxidation of BCCA produces more energy than complete oxidation of glucose in the form of ATP (Monirujjaman and Ferdouse, 2014) and this partly explains the comparative energy efficiency of most efficient cows. ...
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The opportunity to select for feed efficient cows has been limited by inability to cost-effectively record individual feed efficiency on an appropriate scale. This study investigated the differences in milk metabolite profiles between high- and low residual feed intake (RFI) categories and identified biomarkers of residual feed intake and models that can be used to predict residual feed intake in lactating Holsteins. Milk metabolomics analyses were undertaken at early, mid and late lactation stages and residual feed intake was calculated in 72 lactating dairy cows. Cows were ranked and grouped into high residual feed intake (RFI >0.5 SD above the mean, n = 20) and low residual feed intake (RFI <0.5 SD below the mean, n = 20). Milk metabolite profiles were compared between high residual feed intake (least efficient) and low residual feed intake (most efficient) groups. Results indicated that early lactation was predominantly characterized by significantly elevated levels of medium chain acyl carnitines and glycerophospholipids in high residual feed intake cows. Citrate cycle and glycerophospholipid metabolism were the associated pathways enriched with the significantly different metabolites in early lactation. At mid lactation short and medium chain acyl carnitines, glycerophospholipids and amino acids were the main metabolite groups differing according to residual feed intake category. Late lactation was mainly characterized by increased levels of amino acids in high residual feed intake cows. Amino acid metabolism and biosynthesis pathways were enriched for metabolites that differed between residual feed intake groups at the mid and late lactation stages. Receiver operating characteristic curve analysis identified candidate biomarkers: decanoylcarnitine (area under the curve: AUC = 0.81), dodecenoylcarnitine (AUC = 0.81) and phenylalanine (AUC = 0.85) at early, mid and late stages of lactation, respectively. Furthermore, panels of metabolites predicted residual feed intake with validation coefficient of determination ( R ² ) of 0.65, 0.37 and 0.60 at early, mid and late lactation stages, respectively. The study sheds light on lactation stage specific metabolic differences between high-residual feed intake and low-residual feed intake lactating dairy cows. Candidate biomarkers that distinguished divergent residual feed intake groups and panels of metabolites that predict individual residual feed intake phenotypes were identified. This result supports the potential of milk metabolites to select for more efficient cows given that traditional residual feed intake phenotyping is costly and difficult to conduct in commercial farms.
... BCAAs belong to the proteinogenic amino acids category (19). They play a role in several physiological and metabolic mechanisms, such as promoting protein synthesis and degradation in skeletal muscles and other tissues, hormone production, detoxification of nitrogenous wastes, wound healing, initiating signaling pathways, regulating gene expression, cell apoptosis and regeneration, insulin resistance, and glucose metabolism (20)(21)(22). BCAAs can promote glycogen sparing, and there is a close association between BCAAs, brain levels of tryptophan, and serotonin (23). The oxidation of BCAAs primarily occurs in skeletal muscles by specific enzymes, enhancing fatty acid oxidation and preventing obesity. ...
... The oxidation of BCAAs primarily occurs in skeletal muscles by specific enzymes, enhancing fatty acid oxidation and preventing obesity. However, other amino acids are catabolized in the liver (20). BCAAs also participate in immune system processes. ...
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Branched-chain amino acids (BCAAs), including valine, leucine, and isoleucine, are crucial amino acids with significant implications in tumorigenesis across various human malignancies. Studies have demonstrated that altered BCAA metabolism can influence tumor growth and progression. Increased levels of BCAAs have been associated with tumor growth inhibition, indicating their potential as anti-cancer agents. Conversely, a deficiency in BCAAs can promote tumor metastasis to different organs due to the disruptive effects of high BCAA concentrations on tumor cell migration and invasion. This disruption is associated with tumor cell adhesion, angiogenesis, metastasis, and invasion. Furthermore, BCAAs serve as nitrogen donors, contributing to synthesizing macromolecules such as proteins and nucleotides crucial for cancer cell growth. Consequently, BCAAs exhibit a dual role in cancer, and their effects on tumor growth or inhibition are contingent upon various conditions and concentrations. This review discusses these contrasting findings, providing valuable insights into BCAA-related therapeutic interventions and ultimately contributing to a better understanding of their potential role in cancer treatment.
... g/100 g) compared to other fruits which range from 0.50 g/100 g to 9.80 g/100 g. Amino acids act as a building block of muscles, help maintain muscle mass, promote muscle growth, lower blood pressure, and help in the growth, and maintenance of tissues, boost metabolism, and help burn fat (Monirujjaman & Ferdouse 2014). Myrica esculenta fruits are also a rich source of phytochemicals such as L-hydroxyproline, iso-leucine, valine, L-cysteine hydroxy-chloride, alanine, tryptophan, glutamic acid, tyrosine, threonine, leucine, and lysine monochloride (Rawat et al. 2013;Sood & Shri 2018;Kabra et al. 2019;Anjum & Tripathi 2021). ...
... Phosphorous helps to make energy, move muscles, keep bones and teeth strong, reduce muscle pain, help filter waste, repair tissue and cells, and manage how the body stores and uses energy. It maintains a regular heartbeat, acts as a genetic building block, and produces DNA and RNA; it also helps in the balance and use of other vitamins (B and D) and minerals (I, Mg, and Zn) (Monirujjaman & Ferdouse 2014). Phosphorous and iron concentration ranges from 0.02 g/100 g to 5.62 g/100 g and 0.09 g/100 g to 3.26 g/100 g, respectively. ...
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Wild and underutilized plants bearing fruits widely grow throughout the northern Himalayas, including Himachal Pradesh, Jammu and Kashmir, Ladakh, and Uttarakhand states of India. The fruits of these plants have the potential for rural development in Northern Himalayas by developing more commercial products. Ficus auriculata, Rubus ellipticus, Myrica esculenta, Ficus palmata, Pyracantha crenulate, Prunus armeniaca, Berberis asiatiica, Pyrus pashia, Rubus niveus, Carissa spinarum, Cordia dichotoma, Flacourtia indica, Malus sikkimensis, Olea ferruginea, Elaeagnus latifolia, Corylus jacquemontii, and Pinus gerardiana are some examples of the plant species. Local people mainly consume the fruits of these plant species and a few of them are used for diferent processed food items such as jam, jelly, juice, squash, and sauce on a small scale. Therefore, fruits of wild and underutilized plants have potential nutritional values. They are widely used as sources of protein, fat, carbohydrate, macronutrients, and micronutrients. These fruits also contain multipurpose and diversifed classes of phytochemical compounds such as favonoids, tannins, terpenoids, saponins, glycosides, and alkaloids, which are applied to treat various human and livestock health ailments. The extracts of underutilized fruits are widely applied to treat cold, fever, fertility disorders, diabetes, and skin diseases. Their phytochemical compounds also demonstrated antipyretic, analgesic, anti-infammatory, anticancer, antimicrobial, antiplasmodial, and antinociceptive activities. Thus, this review highlights the current research status about the nutritional profling, chemical composition, and utilization of these valuable fruits efectively/adequately to develop new food and pharmaceutical products.
... The BCAAs cannot be synthesized de novo in mammals [10]. In the brain, BCAAs may have a role in the synthesis of neurotransmitters and the production of energy [11]. Experimental data have shown that besides leucine, both valine and isoleucine have antiepileptic properties of their own [12]. ...
Autism spectrum disorder (ASD) and epilepsy run hand-to-hand in their pathophysiology. Epilepsy is not an uncommon finding in patients with ASD. The aim of the present study was to identify the metabolic abnormalities of BCAAs (leucine, isoleucine, and valine) in children with ASD with and without seizures in comparison with neurotypical controls. Also, this study aimed to investigate the presence of epileptiform discharges on electroencephalography (EEG) in ASD patients and to describe the types and frequency of seizures observed. The study included 90 children aged 2-7 years, 30 of whom were diagnosed with both ASD and epilepsy. The other 30 children were diagnosed as ASD without epilepsy, and a comparable 30 normally developed children served as a control group. The groups were matched by age and gender. All patients were referred to the Autism Disorders Clinic for interviews and examinations. The Childhood Autism Rating Scale (CARS) was applied to all study participants to assess the degree of autism. The present study results show that all types of seizures may be identified in ASD children. The median serum levels of BCAAs were lower in ASD children with and without epilepsy than in neurotypical controls. This opens the door for discussion about new etiologies and better categorizations of ASD based on genotype and genetic abnormalities detected. More studies with larger samples are needed to understand ASD better and to more reliable evaluate the association between ASD, EEG changes, seizures, and BCAAs.
... The calculated value of Isoleucine to leucine ratio (BCAA) was found higher in sorghum (16.06) and lowest in oat (0.53). Branched chained amino acids are mainly used for muscle tissues buildup due to role in promoting protein synthesis and glucose metabolism [22]. BCAA is widely used by athletes to prevent degradation of muscle proteins and for building endurance. ...
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The study was done on the characterization of Millets for their chemical and amino acid composition, total amino acid profile and amino acid scoring. The analyzed millet grains depicted moisture content less than 10 % that ensured higher storage stability. Pearl millet and sorghum had the most desirable amino acid composition. Non-essential amino acid content dominated the overall amino acid profile in analyzed pearl millet, finger millet and sorghum. Pearl millet and sorghum proteins was found to have an Essential amino acid index (EAAI) value of greater than 90 and thus are considered as good quality proteins. Sorghum was found to contain isoleucine as its limiting amino acid. The analyzed millets were found to contain higher amounts of tyrosine than phenylalanine, thus the consumptions of these cereals could be beneficial for those suffering from phenylketonuria. Oats and Finger millet were found to contain lowest concentration of sulphur containing essential amino acids cysteine and methionine.
... The PI3K signaling pathway plays a role in regulating cell growth and glucose metabolism [176]. It impacts protein synthesis through the mTOR enzyme and influences glucose uptake and utilization [177]. Activation of the PI3K pathway renders cancer cells dependent on high glucose flux [178]. ...
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Cancer is one of the leading causes of death worldwide, affecting millions of people each year. Fortunately, the last decades have been marked by considerable advances in the field of cancer therapy. Researchers have discovered many natural substances, some of which are isolated from plants that have promising anti-tumor activity. Among these, essential oils (EOs) and their constituents have been widely studied and shown potent anticancer activities, both in vitro and in vivo. However, despite the promising results, the precise mechanisms of action of EOs and their bioactive compounds are still poorly understood. Further research is needed to better understand these mechanisms, as well as their effectiveness and safety in use. Furthermore, the use of EOs as anticancer drugs is complex, as it requires absolute pharmacodynamic specificity and selectivity, as well as an appropriate formulation for effective administration. In this study, we present a synthesis of recent work on the mechanisms of anticancer action of EOs and their bioactive compounds, examining the results of various in vitro and in vivo studies. We also review future research prospects in this exciting field, as well as potential implications for the development of new cancer drugs.
... When compared to the total AAs, the content of lysine in saltbush was higher (6.3 mg/g DW and 7% of total AAs) than whey protein (2.6%; [38]). The high content of leucine, isoleucine, and valine in plant foods is important as these branched chain AAs are involved in protein synthesis turnover and signaling and glucose metabolism in humans [39]. ...
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Halophytes are considered emerging functional foods as they are high in protein, minerals, and trace elements, although studies investigating halophyte digestibility, bioaccessibility, and intestinal absorption are limited. Therefore, this study investigated the in vitro protein digestibility, bioaccessibility and intestinal absorption of minerals and trace elements in saltbush and samphire, two important Australian indigenous halophytes. The total amino acid contents of samphire and saltbush were 42.5 and 87.3 mg/g DW, and even though saltbush had a higher total protein content overall, the in vitro digestibility of samphire protein was higher than the saltbush protein. The in vitro bioaccessibility of Mg, Fe, and Zn was higher in freeze-dried halophyte powder compared to the halophyte test food, suggesting that the food matrix has a significant impact on mineral and trace element bioaccessibility. However, the samphire test food digesta had the highest intestinal Fe absorption rate, whereas the saltbush digesta exhibited the lowest (37.7 vs. 8.9 ng/mL ferritin). The present study provides crucial data about the digestive "fate" of halophyte protein, minerals, and trace elements and increases the understanding of these underutilized indigenous edible plants as future functional foods.
... It was noted that when entering the brain, BCAAs and AAAs compete for the same transport protein, while BCAAs are involved in protein synthesis, neurotransmitters, and energy production [37]. The recovery period of rats after exposure to TAA was accompanied by a slight increase (up to~40%) in the content of BCAAs alongside a decrease in AAAs (~7-10%). ...
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Citation: Shurubor, Y.I.; Rogozhin, A.E.; Isakova, E.P.; Deryabina, Y.I.; Krasnikov, B.F. Residual Amino Acid Imbalance in Rats during Recovery from Acute Thioacetamide-Induced Hepatic Encephalopathy Indicates Incomplete Healing. Int. J. Mol. Sci. 2023, 24, 3647. https://doi. Abstract: The delayed consequences of the influence of hepatic encephalopathy (HE) on the metabolism of animals have not been studied enough. We have previously shown that the development of acute HE under the influence of the thioacetamide (TAA) toxin is accompanied by pathological changes in the liver, an imbalance in CoA and acetyl CoA, as well as a number of metabolites of the TCA cycle. This paper discusses the change in the balance of amino acids (AAs) and related metabolites, as well as the activity of glutamine transaminase (GTK) and ω-amidase enzymes in the vital organs of animals 6 days after a single exposure to TAA. The balance of the main AAs in blood plasma, liver, kidney, and brain samples of control (n = 3) and TAA-induced groups (n = 13) of rats that received the toxin at doses of 200, 400, and 600 mg/kg was considered. Despite the apparent physiological recovery of the rats at the time of sampling, a residual imbalance in AA and associated enzymes persisted. The data obtained give an idea of the metabolic trends in the body of rats after their physiological recovery from TAA exposure and may be useful for prognostic purposes when choosing the necessary therapeutic agents.
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The nutritional compositions of fatty acids (FAs), amino acids (AAs), polysaccharides, and phenolic compounds from brown seaweeds Cystoseira trinodis, Dictyota cervicornis , Padina gymnospora and Turbinaria oranata were studied, and their antioxidant and antimicrobial activities were evaluated. The lipophilic profile of D. cervicornis and T. oranata showed richness in saturated FAs (48.13 and 42.41%, respectively) mainly comprised of palmitic acid (16:0) with the proportions 38.4 and 33.79%, respectively. In contrast, C. trinodis and P. gymnospora revealed the highest amounts of unsaturated FAs (51.5 and 38.15%, respectively), constituted mainly of oleic acid (18:1, n9) with proportions 18.29 and 33.79%, respectively. Phytol, cholest-5-en-3-ol, β-stigmasterol and 9Z-octadecenamide were recorded as major unsaponifiable-lipid constituents. The major phenolic compounds were gallic acid in D. cervicornis , catechin in T. oranata and C. trinodis , and kaempferol in P. gymnospora with values of 227.54, 209.63, 167.18 and 85.82µg/g, respectively. The backbone of the polysaccharides in P. gymnospora was galactose (26.5%), ribose (38.9%) in C. trinode , mannose (49.7%) in D. cervicornis , and rhamnose (30.7%) in T. oranata . The major essential AAs were leucine and phenylalanine, while proline was the major non -essential AAs in all species. The MeOH extracts of T. oranata and C. trinodis displayed mild antioxidant activity with IC 50 values of 26.1 and 30.5µg/ml. FAs contents of C. trinodis and D. cervicornis exhibited antibacterial activities against Staphylococcus aureus and Bacillus cereus , while FAs contents of T. oranata and P. gymnospora exhibited potent antifungal activities against Penicillium expansum and Syncephalastrum racemosum with inhibition MIC value for both = 0.312mg/ml.
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Autism spectrum disorders (ASD) are neurodevelopmental diseases that manifest themselves at early ages as insufficient social and communicative skills, repetitive sensory-motor behaviors and restricted interests, and peculiar combinations of these traits. Autism prevalence in wealthy nations is currently rising. Due to increasing numbers of diagnosis, studies on the genetic background of autism have gained momentum recently. Especially the research on mitochondrial dysfunction and mammalian target of rapamycin (mTOR) is important in that it might provide a great contribution to the ASD field for new treatment resources.
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The obesity and diabetes epidemics are continuing to spread across the globe. There is increasing evidence that diabetes leads to a significantly higher risk for certain types of cancer. Both diabetes and cancer are characterized by severe metabolic perturbations and the branched chain amino acids (BCAAs) appear to play a significant role in both of these diseases. These essential amino acids participate in a wide variety of metabolic pathways, but it is now recognized that they are also critical regulators of a number of cell signaling pathways. An elevation in branched chain amino acids has recently been shown to be significantly correlated with insulin resistance and the future development of diabetes. In cancer, the normal demands for BCAAs are complicated by the conflicting needs of the tumor and the host. The severe muscle wasting syndrome experience by many cancer patients, known as cachexia, has motivated the use of BCAA supplementation. The desired improvement in muscle mass must be balanced by the need to avoid providing materials for tumor proliferation. A better understanding of the complex functions of BCAAs could lead to their use as biomarkers of the progression of certain cancers in diabetic patients.
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Branched chain amino acids (BCAAs) have been shown to affect gene expression, protein metabolism, apoptosis and regeneration of hepatocytes, and insulin resistance. They have also been shown to inhibit the proliferation of liver cancer cells in vitro, and are essential for lymphocyte proliferation and dendritic cell maturation. In patients with advanced chronic liver disease, BCAA concentrations are low, whereas the concentrations of aromatic amino acids such as phenylalanine and tyrosine are high, conditions that may be closely associated with hepatic encephalopathy and the prognosis of these patients. Based on these basic observations, patients with advanced chronic liver disease have been treated clinically with BCAA-rich medicines, with positive effects.
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Insulin resistant or obese individuals have increased serum BCAA levels. Recent findings relate increased BCAA catabolism to increased fatty acid oxidation and better metabolic health in physically active individuals. We hypothesize that via glyceroneogenesis, BCAA catabolism mediates increased constitutive use of fatty acids for β-oxidation in subjects with increased inherent or acquired aerobic capacity both during exercise and at rest.Summary for the table of contentsThis article presents the hypothesis that skeletal muscle BCAA catabolism mediates increased constitutive use of fatty acids for β-oxidation.
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Objective: Metabolic profiling of small molecules offers a snapshot of physiological processes. To identify metabolic signatures associated with type 2 diabetes and impaired fasting glucose (IFG) beyond differences in glucose, we used mass spectrometry-based metabolic profiling. Research design and methods: Individuals attending an institutional health screen were enrolled. IFG (n = 24) was defined as fasting glucose (FG) of 6.1 to 6.9 mmol/L and 2-hour post glucose load <11.1 mmol/L or glycosylated hemoglobin <6.5%, type 2 diabetes (n = 27), FG ≥7.0 mmol/L, or 2-hour post glucose load ≥11.1 mmol/L, or glycosylated hemoglobin ≥6.5%, and healthy controls (n = 60), FG <6.1 mmol/L. Fasting serum metabolomes were profiled and compared using gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry. Results: Compared to healthy controls, those with IFG and type 2 diabetes had significantly raised fructose, α-hydroxybutyrate, alanine, proline, phenylalanine, glutamine, branched-chain amino acids (leucine, isoleucine, and valine), low carbon number lipids (myristic, palmitic, and stearic acid), and significantly reduced pyroglutamic acid, glycerophospohlipids, and sphingomyelins, even after adjusting for age, gender, and body mass index. Conclusions: Using 2 highly sensitive metabolomic techniques, we report distinct serum profile change of a wide range of metabolites from healthy persons to type 2 diabetes mellitus. Apart from glucose, IFG and diabetes mellitus are characterized by abnormalities in amino acid, fatty acids, glycerophospholipids, and sphingomyelin metabolism. These early broad-spectrum metabolic changes emphasize the complex abnormalities present in a disease defined mainly by elevated blood glucose levels.
A prospective, randomized, double-blind trial of the nutritional effects of branched chain modified amino acid solutions was undertaken in 23 surgical patients within 24 hours of the onset of major general surgery, polytrauma, or sepsis. The effects were evaluated in the absence of abnormalities of oxygen transport and perfusion in an isocaloric/isonitrogenous setting where the major difference between the groups was the amount of branched chain amino acids received. Both groups received balanced parenteral nutrition with 1.5 gm/kg/day of amino acids, 30 calories/kg/day of glucose, and 7 calories/kg/day of fat. At the end of the 7-day study interval, the group receiving the branched chain enriched therapy at 0.7 gm/kg/day of branched chain amino acids had improved nitrogen retention; an elevation of their absolute lymphocyte count from 800 to 1800/mm3, a reversal of anergy to recall skin test antigens in 60% of the patients, and improved plasma transferrin levels (p < 0.03). Nutritional support using the modified amino acid metabolic support solutions has beneficial effects during the stress interval that do not seem as achievable with current commercially available nutritional support regimens.
There is burgeoning evidence that branch chain amino acids (BCAAs) are biomarkers of metabolic, cardiovascular, renal and cerebrovascular disease. The purpose of this review is to summarize the current evidence in this area. Recent evidence demonstrates that BCAAs are associated with insulin resistance, type 2 diabetes, risk of cardiovascular disease, stage I and II chronic kidney disease and ischemic stroke. Further, circulating levels of BCAAs have the potential to predict populations at risk for cardiometabolic disease, type 2 diabetes and mortality from ischemic heart disease. Importantly, the relationship of BCAAs to insulin resistance is affected by the intake of fat in the diet as well as age. Current evidence supports the potential use of BCAAs as biomarkers of disease. However, questions regarding the mechanisms underlying the relationship of BCAAs to disease process and severity need to be answered prior to the use of BCAAs as a biomarker in clinical practice.
In order to assess the effects of a branched chain amino acid (BCAA) enriched solution on urinary nitrogen loss and muscle protein breakdown, 22 burnt patients were randomly divided into two groups immediately after hospital admission : 11 patients received a 22% BCAA amino acid solution, 11 patients received a 41% BCAA amino acid solution. Nitrogen intake was 0.2 g per day during the first 4 days in each group. Urinary total nitrogen, urinary creatinine and urinary 3,methylhistidine (3,MeHis) were measured for 4 days. Nitrogen balance, 3,MeHis/nitrogen ratio and 3,MeHis/creatinine ratio were calculated in each group. The two groups were compared using Student's test. Nitrogen, creatinine and 3,MeHis urinary excretion, and nitrogen balance were not significantly different in the two groups, except for urinary nitrogen on day 3 which was slightly higher in the 41% BCAA group. The 3,MeHis/nitrogen ratio on day 1, day 2 and during the whole study period, as well as the 3,MeHis/creatinine ratio on day 2, were significantly lower in the 41% BCAA group. These results were in agreement with a decrease in muscle/whole body urinary nitrogen excretion. However, no beneficial effect upon nitrogen loss or nitrogen balance was shown by using the 41% BCAA rich amino acid solution.
Oxidative stress (OS) plays an important role in the progression of chronic liver disease including organ injury and hypoalbuminemia. Long-term oral supplementation with branched-chain amino acids (BCAAs) can inhibit liver dysfunction but their role in the prevention of liver fibrosis and injury to the liver is unclear. The aim of this study was to assess how BCAAs preserve liver function from OS. To investigate how BCAAs specifically prevent OS, we evaluated the effect of oral supplementation with BCAAs on OS using a rat liver cirrhosis model. Liver cirrhosis was induced in ten male Sprague-Dawley rats by administering carbon tetrachloride for 12 weeks. Five of the ten carbon tetrachloride-treated rats were assigned to a control group and five to a BCAA group. BCAA-supplementation significantly preserved plasma albumin concentrations and significantly inhibited the occurrence of organ injury as determined by blood chemistry analysis. Hepatic expression of OGG1 mRNA was increased in the BCAA group compared to the control group. In the BCAA group, increased hepatic levels of OGG1 protein were found by western blot. On the other hand, the number of 8-OHdG-positive cells was significantly higher in liver sections taken 1 month after carbon tetrachloride treatment. Furthermore, OGG1-positive cells were significantly increased in the hepatocytes around the central vein. BCAA was found to reduce OS, which could possibly lead to a decrease in the occurrence of hypoalbuminemia and organ injury. Our results indicate that BCAA-enriched nutrients stimulate antioxidant DNA repair in a rat model of liver injury induced by carbon tetrachloride.