Istilah SEMUT JEPANG sudah banyak digunakan oleh masyarakat, tapi sebenarnya tidak mencirikan sebagai semut. Lebih cocok disebut kutu beras Tenebrio Molitor.
Perbedaan dari semut
Jepang dibandingkan semut spesies lainnya yakni memiliki badan yang keras,
bersayap namun tak bisa terbang, suka reproduksi, hidup secara berkelompok,
bukan hewan kanibal.
Sumber : http://semutjepangdibogor.blogspot.com/2015_02_01_archive.html
BBPPTP Ambon, Ulat tepung (Tenebrio molitor) dikenal
juga oleh kebanyakan masyarakat sebagai ulat hongkong. Imago dari serangga ini
berupa kumbang yang termasuk dalam genusTenebrio yang
memiliki warna merah kehitaman, hitam atau coklat gelap dan panjangnya
13-17 mm (Borror et
al., 1982).
Sumber : http://ditjenbun.pertanian.go.id/bbpptpambon/berita-309-tenebrio-molitor-hama-pascapanen-yang-bermanfaat.html
Ciri dari semut jepang ini secara umum adalah memiliki tubuh berwarna hitam kecoklatan, berkaki enam dan tekstur tubuhnya cenderung keras. Hewan ini memiliki sayap yang mirip dengan kumbang. Namun semut jepang tidak dapat terbang seperti serangga bersayap lainya.
Sumber : http://mulaiusaharumahan.blogspot.com/2014/10/cara-budidaya-semut-jepang.html
Keunikan khas Semut jepang
Semut jepang memiliki ciri atau tanda seperti:
- Suka atau cepat berkembangbiak
- Hidup berkoloni atau berkelompok
- Ruas badan lebih besar dari ruas kepala
- Ukuran tubuh kecil hanya beberapa milimeter
- Bukan tipe hewan pemakan daging/sesama
- Memiliki sayap tapi tidak bisa terbang
- Makanan ragi tape
- Memiliki badan yang keras,
- Memiliki kaki 6
Sumber : http://www.mearindo.com/2014/11/semut-jepang-solusi-untuk-asam-urat.html
Manfaat dan kegunaan dari semut Jepang menurut http://tipsdantrikampuh.blogspot.com/2014/09/manfaat-dan-kegunaan-dari-semut-jepang.html, adalah :
- Semut Jepang berguna untuk menjadikan tingkat kolesterol di darah normal, khususnya untuk orang yang mempunyai kadar kolesterol tinggi pada darah.
- Mengobati dan meringankan penyakit jantung.
- Mengobati dan meringankan penyakit asam urat, khusus orang dengan kadar asam urat tinggi di tubuh.
- Menjadikan jumlah gula di darah menjadi stabil, cocok untuk orang yang terserang penyakit diabetes.
- Menjadikan tekanan darah stabil, khususnya untuk orang yang menderita hipertensi (penyakit darah tinggi).
- Mampu menambah vitalitas dari pria maupun wanita, cocok bagi pria maupun wanita dengan jam kerja tinggi serta kesibukan untuk sehari-harinya, tubuh pun dapat menjadi lebih segar dengan semut Jepang.
Manfaat semut Jepang berdasarkan kajian ilmiah, kami paparkan sebagai berikut :
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Sumber : http://en.cnki.com.cn/Article_en/CJFDTOTAL-HBNS200201007.htm
Hasilnya penelitian menunjukkan bahwa fungsi Tenebrio molitor pada tikus adalah dapat meningkatkan pertumbuhan, meningkatkan kemampuan belajar dan menghafal serta merupakan anti kelelahan dan kekurangan oksigen dan meningkatkan intelegent.
Sumber : http://en.cnki.com.cn/Article_en/CJFDTOTAL-HBNS200201007.htm
Hasilnya penelitian menunjukkan bahwa Tenebrio molitor merupakan protein alami berkualitas tinggi, namun penggunaannya baru sebatas hal yang terkait dengan kesehatan - karena keterbatasan teknologi.
Sumber : http://en.cnki.com.cn/Article_en/CJFDTOTAL-HBNS200703007.htm
Sumber : http://en.cnki.com.cn/Article_en/CJFDTOTAL-SPKJ200904103.htm
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Characteristics of Maize Flour Tortilla Supplemented with Ground Tenebrio molitor Larvae
Instituto Tecnológico de Celaya, Avenida Tecnológico s/n, Celaya, Guanajuato 38010, México; Departamento de Biotecnología y Bioquímica, CINVESTAV-IPN, Km. 9.6 Libramiento Norte Carretera Irapuato-León, Irapuato, Guanajuato 36500, Mexico; and CES Internacional and Asociados, Cirilo Conejo 6, Querétaro, Querétaro, México
Abstract
The larva of the Tenebrio molitor, known as the yellow meal worm,
is a plague of wheat and flours. Consumption of the raw insects is not
well accepted because of their appearance. The objective of the present
work was to grow T. molitor larvae under standard conditions, to
analyze the chemical composition of the larvae powder, and to prepare
supplemented maize tortillas. Protein and fat contents were performed
with standard methods. Tenebrio larvae powder had a 58.4% protein
content; this protein was rich in essential amino acids such as
phenylalanine, tyrosine, and tryptophan; the found values satisfied
those recommended by the Food and Agriculture Organization. Fatty acid
composition was determined by GC-MS showing high contents of oleic acid
and linoleic acid (19.8 and 8.51%, respectively). A large proportion of
unsaturated fatty acids of longer chains was detected. Long-chain fatty
acids having two or three double bonds have been claimed as highly
beneficial to health. Tortillas supplemented with larvae powder had
excellent consumer acceptance, and tortilla protein content increased by
2% as well as the amount of essential amino acids. These results show
new ways to consume insects and at the same time increase the
nutritional value of the original food products.
Sumber : http://pubs.acs.org/doi/pdf/10.1021/jf010691y
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Energy-efficient food production to reduce global warming and ecodegradation: The use of edible insects
Shri Manakula Vinayagar College of Engineering and Technology, Puducherry, India.
Abstract
As
the global population continues to rise, and attempts to increase
arable land area come in sharp conflict with the necessity to retain
forests on one hand and pressures of urbanization on the other, the wave
of global food shortage that has hit the world recently is likely to
hit us again and again.
The increasing pressure on land is making meat production from macro-livestock
less sustainable than ever before. To add to the diminishing pastures
and broadening demand-supply gap of food grains are the shortages
arising due to the diversion of some of the food crops for biofuel
production. There is also an increasing use of fodder for generating
biomass energy.
The result is that even as the demand for animal protein keeps on
rising with the swelling global population, there is every possibility
that attempts to meet this demand would face serious crises in the
coming years. The adverse impacts of global warming are conspiring to make the situation even worse than it otherwise would have been.
The
present review brings home the fact that one of the possible ways to
get around this problem is to extend the practice of entomophagy – use
of insects as human food. As of now entomophagy is practiced in some regions
and some cultures, but, by-and-large, the bulk of global population
stay away from it. It is even looked down in several cultures and
forbidden in some others. The review brings out the irrationality of
omitting edible insects from human diet
given the generally higher quality of nutrition they contain as
compared to food based on macro-livestock. This aspect, coupled with
much lesser consumption of energy and natural resources associated with
insect-based protein production, makes entomophagy an option which
deserves urgent global attention.
The authors
highlight the relatively stronger sustainability of animal protein
production by way of insect farming because, pound to pound, the
production of insect protein takes much less land and energy than the more
widely consumed forms of animal protein. It is estimated that over a
thousand insect species are already a part of human diet and the
nutrition offered by several of the species matches or surpasses that
which is contained in traditional non-vegetarian foods. The paper also
deals with the relevance of entomophagy as a potentially more
ecologically compatible and sustainable source of animal protein than
the red and the white meat on which most of the world presently depends.
In the emerging global pattern based on an expanding share of renewable
energy sources, entomophagy fits in as a renewable source of food
energy for the future.
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Larvae of mealworm (Tenebrio molitor L.) as European novel food
Copyright © 2013 Ewa Siemianowska et al. This 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.
ABSTRACT
For centuries, insects have been used as
food due to their availability
and
easiness in raising that is much less burdensome
for environment than animal husbandry
breeding. Mealworm (Tenebrio molitor L.)
is a store-pest
of which larvae are consumed
by people. The aim of the
work
was to determine the nutritional value of
larvae
of mealworm (Tenebrio
molitor L.). The material was a three-month-old
mealworm larva
25 -
30 mm in length.
Larvae were boiled
for 3 min and next dried in 60˚C. Contents of water, ash,
minerals, protein, fat and fat acids profile have been determined. Fresh larvae contained 56% of
water, 18% of total protein, 22% of total fat and
1.55% of ash. High contents of minerals
were found in the larvae: magnesium (87.5
mg/100g), zinc (4.2 mg/100g), iron (3.8 mg/100g), copper (0.78 mg/100g) and manganese (0.44
mg/100g). The proportion of n-6/n-3 fatty acids was very
advantageous and amounted to
6.76. Larvae powder
contained twice higher
content of protein, fat, ash and minerals. Larva
of mealworm is a valuable
source of nutrients in amounts more profitable for human organism than
traditional meat food. Powdered larva is a high-grade
product to be applied as a supplement to traditional meals.
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A digestive prolyl carboxypeptidase in
Tenebrio molitor larvae
Irina A. Goptar a, Dmitry A. Shagin b, c, Irina A. Shagina c, Elena S. Mudrik c, Yulia A. Smirnova d, Dmitry P. Zhuzhikov e, Mikhail A. Belozersky d, Yakov E. Dunaevsky d, Brenda Oppert f, *, Irina Yu. Filippova a, Elena N. Elpidina d
a Chemical Faculty, Moscow State University, Moscow 119991, Russia
b
Shemiakin and Ovchinnikov Institute of Bioorganic Chemistry
RAS, Miklukho-Maklaya
16/10, 117997
Moscow, Russia
c Evrogen JSC, Miklukho-Maklaya 16/10, 117997 Moscow, Russia
d
A.N. Belozersky Institute
of Physico-Chemical Biology, Moscow
State University, Moscow 119991, Russia
e Biological Faculty, Moscow State University, Moscow 119991, Russia
f USDA Agricultural Research Service,
Center for Grain and Animal Health Research, 1515 College Ave., Manhattan, KS 66502, USA
ABSTRACT
Prolyl carboxypeptidase (PRCP) is a lysosomal proline specific serine peptidase
that also plays a vital role in the regulation of physiological processes in mammals. In this report, we
isolate and characterize the
first
PRCP in an insect. PRCP was purified from the anterior
midgut of larvae of
a stored product pest, Tenebrio molitor, using a three-step chromatography strategy,
and it
was determined that the purified enzyme was a dimer. The
cDNA
of
PRCP was cloned and sequenced, and the predicted protein was identical to the proteomic sequences of the purified enzyme. The substrate specificity and kinetic parameters of the enzyme were determined. The T. molitor PRCP participates in
the hydrolysis of
the insect’s major dietary
proteins, gliadins, and is
the first PRCP to be ascribed a digestive function. Our collective data suggest that the evolutionary enrichment of the digestive peptidase complex in
insects with an area of acidic to
neutral pH in the midgut is a result of the incorporation of
lysosomal peptidases,
including PRCP.
Introduction
Prolyl carboxypeptidase (PRCP; PCP, lysosomal carboxypeptidase,
angiotensinase C,
EC 3.4.16.2) belongs to a
group of proline specific peptidases (PSP) (Cunningham and O’Connor, 1997) that are involved
in the regulation of various
metabolic processes (Vanhoof et al., 1995). PSP represent a relatively small group of highly specific exo- and endo-peptidases that cleave bonds formed by
proline residues in
proteins and peptides. The unique activity of PSP is due to the structural features of proline, the only cyclic imino acid among 20 α amino acids found in
proteins and peptides. Peptide bonds containing proline residues are not hydrolyzed efficiently by most peptidases, and a proline residue in the peptide chain serves to protect against
degradation by enzymes with broad specificity. The ability of PSP to hydrolyze this bond determines the specific activity of the enzyme in
the
regulation of metabolic processes.
PRCP are serine peptidases that catalyze the cleavage of a substrate at the C-terminal amino acid linked to a
proline residue. At present, only PRCP from human (Odya et al., 1978; Tan et al., 1993; Shariat- Madar et al., 2002), pig (Yang et al., 1970; Kakimoto et al., 1973), monkey (Suzawa et al., 1995), and bacterium Xanthomonas malto- philia (Suga et al., 1995) have been isolated and studied. The primary structure of the isolated enzyme, present as
a dimer in solution, has been described only for human PRCP, and the enzyme was assigned to the S28
family of serine peptidases (Tan et al., 1993). The crystal structure was solved recently and revealed that PRCP has
a unique peptidase structure, with closest identity to dipeptidyl peptidase 7
(DPP7), containing a conserved a/b hydrolase domain and a
novel helical SKS domain that caps the active site with the catalytic Ser-Asp- His triad (Abeywickrema et al., 2010; Soisson et al., 2010).
PRCP is widely distributed in human tissues,
but mostly it is localized to the lungs, liver
and placenta (Tan et al., 1993). The
enzyme was initially found in human lysosomes (Yang et al., 1970; Kumamoto et al., 1981), but later it was found as a membrane-
expressed enzyme in
cultured human umbilical
vein
endothelial cells, explained by
the association of PRCP with specific membrane
proteins after exocytosis (Shariat-Madar et al., 2004).
The exact physiological functions for PRCP are
not completely understood. The
key
role for mammalian PRCP is in regulating
blood
pressure (Kumamoto et al., 1981; Tamaoki et al., 1994; Kaplan and Ghebrehiwet, 2010; Hagedorn, 2011), but PRCP is also involved in processes
of proliferation (Duan et al., 2011), inflammation (Kumamoto et al., 1981; Ngo et al., 2009) and angiogenesis (Mallela et al., 2009). PRCP also regulates food intake by inactivating a- melanocyte stimulating hormone (Wallingford
et al., 2009; Shariat- Madar et al., 2010; Diano, 2011; Jeong et al., 2012). The only report of
insect PRCP details changes in
expression of
the
PRCP gene in response to
magnesium exposure in Culex quinquefasciatus larvae
(Zhao et al., 2010).
The present research on insect PSP
is a part of our studies of digestive enzymes in larvae of the yellow mealworm, Tenebrio molitor (Coleoptera: Tenebrionidae), a pest of processed grains and
stored products. The complex of digestive peptidases
in T. molitor
larvae differs substantially from human
digestive
enzymes, although both the beetle and people have grain products as
a pri- mary food source. The major digestive organ of
the
larvae is the midgut, where a
sharp
pH gradient is found, from 5.6 in the anterior
midgut (AM) to 7.9 in posterior midgut (PM)
(Terra et al., 1985; Vinokurov et al., 2006a; Elpidina and Goptar, 2007). This gradient restricts
the activity of different digestive enzymes in specific compartments of the midgut,
which is usually consistent with the
pH-optima of
their
activity (Vinokurov et al., 2006b).
The major digestive peptidases in
the
AM of T. molitor larvae are cysteine peptidases,
represented by
four
to
six
distinct enzymes
(Terra and Cristofoletti,
1996; Vinokurov et al., 2006a,b; Prabhakar et al., 2007). The major cysteine peptidase activity is cathepsin L (Cristofoletti et al., 2005; Beton et al., 2012; Oppert et al., 2012) known as a lysosomal peptidase in
eukaryotes (Turk et al., 2012). In the PM of
T. molitor larvae, digestive enzymes
are mostly serine
peptidases, including
four trypsin-like
and five chymotrypsin-like
serine
peptidases (Tsybina et al., 2005; Elpidina et al., 2005; Vinokurov et al., 2006a,b) as well
as
a membrane-bound
amino- peptidase (Cristofoletti
and Terra, 1999, 2000) and soluble carboxypeptidase
(Ferreira et al., 1990; Prabhakar et al., 2007).
The
major
dietary proteins of T. molitor larvae,
prolamins, contain 30-50% glutamine
and 10-30% proline residues (Shewry and Tatham, 1990; Shewry and
Halford, 2002). Therefore, we
analyzed
the
major post-glutamine cleaving activities in the T. molitor larval digestive complex
and
found
that
they
were cysteine peptidases (Goptar et al., 2012). Based on the composition
of their diet, we also predicted the occurrence of digestive PSP
in T. molitor larvae. Indeed, we described the first proline-specific digestive peptidase in the midgut, which was a serine peptidase
that specifically cleaved after proline, had an
acidic pH
optimum (5.3), and was found mainly in the AM contents (Goptar et al., 2008a,b), but the enzyme was not identified. In the present
study, we identify this enzyme as a PRCP and detail the substrate speci-
ficity
and kinetic parameters of the first purified
PRCP in an insect. Our data suggest that PRCP is a digestive enzyme in T. molitor larvae, which is
a novel function for PRCP.
Discussion
In this paper, the first PRCP was isolated from an insect, T. molitor larvae. For
PRCP purification, a three-stage scheme was used. The
first
stage was by gel filtration. The
application of this type of
chromatography effectively separated PRCP, with a
molecular mass of 105
kDa,
from the major digestive serine and cysteine endo-
peptidases, with molecular masses less
than 40
kDa
(Vinokurov et al., 2006b) and therefore prevented proteolysis by endopepti-
dases during purification. Additional purification followed with anion exchange and hydrophobic chromatography, resulting in a relatively pure enzyme. The cDNA of the T. molitor larval PRCP was cloned and sequenced, and the identity of
the
predicted PRCP
sequence to the primary structure of
the isolated enzyme was confirmed by mass spectrometry.
The
ratio of the calculated molecular mass of
cloned PRCP and that determined by gel filtration suggests that the enzyme is
a dimer, and similar data are
reported for the human lysosomal PRCP (Odya et al., 1978; Tan et al., 1993). Also similar to the human PRCP, T. molitor PRCP displays acidic pH
optimum at
pH 5.6, correlating with its localization in the acidic AM of T. molitor larvae (Goptar et al., 2008b).
Previously, the primary
structure of the enzyme
was solved only
for human PRCP, and the enzyme was assigned
to the S28 family of serine peptidases (Tan et al., 1993). When PRCP was compared with
annotated sequences of
serine carboxypeptidases and
POP, there
was a
low
degree of
overall identity
(10e18%), but a
high (67%) identity in
active site amino acid residues. The authors concluded that PRCP is an evolutionary link connecting two families,
POP and serine carboxypeptidases, because they possess properties char- acteristic
of both families. Like serine
carboxypeptidases, PRCP
catalyzes the hydrolysis of
a
C-terminal residue that has a free carboxyl group at acidic pH values. On
the other hand,
PRCP hy- drolyzes bonds formed by the carbonyl group of proline residues as
do POP, and a
specific
inhibitor of POP, Z-Pro-prolinal,
inactivates PRCP
as well.
Resolution of the 2.8 A crystal structure of
the
human lysosomal PRCP (Soisson et al., 2010) delineated the structural basis of the different substrate specificities
of the two enzymes
comprising the unique S28 family of PSP: carboxypeptidase PRCP and aminopep-
tidase DPP7.
PRCP has an
extended active-site
cleft that can accommodate proline substrates with multiple
N-terminal resi- dues. In contrast, the substrate binding
groove of DPP7 is occluded
by a short amino acid insertion unique to DPP7 that creates a
truncated active site selective for dipeptidyl proteolysis of
N-ter- minal substrates.
The most specific substrate for T. molitor PRCP was N-protected peptide Z-PF, a selective substrate for
PRCP, but the activity assay with this
substrate was
rather
complicated. Because serine carboxypeptidases,
unlike metallocarboxypeptidases,
are
able to hydrolyze chromogenic p-nitroanilide substrates with a
detectable rate (Scheer et al., 2011), and due to the simplicity of the assay
method, we used these substrates for monitoring of the purifica- tion process and for the study of the substrate specificity. The best chromogenic peptide substrate was Z-AAP-pNA with the highest Vmax/Km value, despite the fact that the substrate
had the lowest
Km value.
The hydrolysis
of
substrates Z-AP-pNA and AP-pNA occurred with equal
efficiency, although Z-AP-pNA was more
tightly bound to the enzyme,
and AP-pNA
was hydrolyzed faster. Lengthening or
shortening
the substrate by one Ala
residue,
substituting Ala at Gly, as well as removing the N-protecting
group all led to an increase of the Km. The maximum rate of hydrolysis of Z-GP-pNA, a specific
substrate
for POP
(Cunningham and O’Connor, 1997) and Z-P-pNA
was an
order of magnitude lower
than
for the other substrates.
Kinetic studies
revealed
complete competitive inhibition of T. molitor PRCP by Z-Pro-prolinal. In
this
type of inhibition, the in- hibitor interacts with the same region of the enzyme that binds substrate. Therefore the inhibitor competes with the substrate for interaction with the enzyme, as do other substrate-like inhibitors
similar to Z-Pro-prolinal.
In contrast to
human PRCP, which specifically functions as a regulatory enzyme affecting
the blood system (Hagedorn, 2011; Adams et al., 2011), the
PRCP from T. molitor is
presumably a digestive enzyme.
Earlier, we described the localization and func- tions of two PSPs from T. molitor larvae (Goptar et al., 2008a,b). We demonstrated that one of the PSPs had an acidic pH optimum, was localized in
the
AM contents, and the activity profile changed in the digestive process similar to the general proteolytic activity, but these data were insufficient
for conclusive identification
of
this peptidase. In this report,
we identified this enzyme as PRCP and further demonstrate that
T. molitor larval
PRCP participates in gliadin hydrolysis that is reduced by
a specific inhibitor of
PRCP Z- Pro-prolinal.
Thus, we have isolated, purified, and identified the primary structure and further
characterized a digestive PRCP from the larval midgut of
an insect pest, T. molitor. The
unique aspects
of this enzyme are
that it is the first PRCP isolated
from an insect, and the first PRCP found to
function as a secreted digestive enzyme. It is unknown if PRCP is involved in digestion in other animals.
Specific digestive peptidases in insects that differentiate
the mode of gliadin hydrolysis from that of
human include cysteine peptidases with post-glutamine cleaving activity (Goptar et al., 2012), and PRCP with post-proline cleaving activity (this report). In
eukaryotic organisms, these enzymes participate in the intracellular lysosomal
degradation of
proteins. Many insects rely
on
typical serine digestive peptidases, trypsin and chymotrypsin, but some groups of
insects with an
area
of acidic to neutral pH in the midgut use cysteine cathepsins also
for digestion (Terra and Ferreira, 1994). Our data
suggest that the enrichment of the peptidase digestive complex in such insects
during evolution
is due to the adaptation of peptidases present in
the
lysosomes of eukaryotic organisms, such as cysteine cathepsins and PRCP.
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APAKAH "Prolyl carboxypeptidase" itu ?
Carboxypeptidase sikat enzim perbatasan pankreas yang membagi satu asam amino pada suatu waktu.
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Supplementation of l-carnitine in athletes:
does it make sense?
Heidrun Karlic, PhD, and Alfred Lohninger,
PhD
From the Ludwig Boltzmann Institute
for Leukemia Research and Hematology, Vienna, Austria; and the Department of Medical Chemistry,
University of Vienna, Vienna, Austria
Abstract
Studies in athletes have shown that carnitine supplementation may foster exercise performance. As reported in the majority of studies, an increase in maximal oxygen consumption and a lowering of the respiratory quotient indicate that dietary carnitine has the potential to stimulate lipid metabolism. Treatment with l-carnitine also has been shown to induce a significant postexercise decrease in plasma lactate, which is formed and used continuously under fully aerobic conditions. Data from preliminary studies have indicated that l-carnitine supplementation can attenuate the deleterious effects of hypoxic training and speed up recovery from exercise stress. Recent data have indicated that l-carnitine plays a decisive role in the prevention of cellular damage and favorably affects recovery from exercise stress. Uptake of l-carnitine by blood cells may induce at least three mechanisms: 1) stimulation of hematopoiesis, 2) a dose-dependent inhibition of collagen-induced platelet aggregation, and 3) the prevention of programmed cell death in immune cells. As recently shown, carnitine has direct effects in regulation of gene expression (i.e., carnitine-acyltransferases) and may also exert effects via modulating intracellular fatty acid concentration. Thus there is evidence for a beneficial effect of l-carnitine supplementation in training, competition, and recovery from strenuous exercise and in regenerative athletics.
Correspondence to: Heidrun Karlic, PhD, Ludwig Boltzmann Institute for Leukemia Research and Hematology, Hanusch Hospital, H. Collinstr. 30, A-1140 Vienna, Austria.
INTRODUCTION
Dietary
supplements to improve performance are familiar to many athletes. Manufacturers
more or less aggressively claim that the substances improve the performance of
athletes (i.e., act as ergo- genic aids) and/or speed up their recovery from
exercise. Most of these claims are
purely speculative and
based on assumptions about how
the dietary supplement
influences metabolism. The substance L-carnitine has been
particularly popular as a potential ergogenic aid because of its role in the
conversion of fat into energy.1,2 For a scheme, the reader is referred to Figure 1.
L-carnitine was first discovered in
muscle extracts by two
Russian scientists3 who named the substance for
the Latin word carnis (flesh or meat). Its chemical structure was established in 1927,
and in 1935 a pioneer article about L-carnitine was published,4 which triggered numerous studies
on the physiological functions of the chemical. In 1959 Fritz showed
that carnitine increases long-chain fatty oxidation in liver and heart.5 Another name for L-carnitine was vitamin BT (T tenebrio) because the larva of black beetle
Tenebrio molitor (Tenebrionidae, Coleoptera) requires L-carnitine as a growth factor in addition to folic acid and other known B vitamins.
Considering the chemical structure, the choline-like metabolite L-carnitine
(3-hydroxy-4-N,N,N- trimethylaminobutyrate,
L-3-hydroxy-4-N-trimethylaminobutyric acid or-trimethylamino- -hydroxybutyric acid) is a quaternary
amine. In phrenic nerve
diaphragm preparations, its effect, namely
induction of tetanic fade, can be reduced by addition of choline.6
FIG. 1. Role of L-carnitine in oxidative
metabolism. L-carnitine’s primary function (blue arrows) is to “shuttle” fatty
acids into the mitochondria by CPT-I. CPT-II mediates
the further progression toward -oxidation. Car- nitine’s secondary function affects
the CoASH/CoA ratio. CoASH is a
two-carbon compound; CoA
is a vitamin
B derivative. Supplemental L-carnitine
can react with some of the excess CoASH groups that accu- mulate during
strenous exercise, thereby producing acetylcarnitine. This lowers the CoASH/CoA
ratio, which in turn activates the enzyme PDH. PDH causes some pyruvate to be
converted to CoASH as opposed to lactic acid. Less lactic acid can mean delayed
fatigue. Further, L-carnitine reacts with the excess CoASH/CoA groups to form
acetylcarnitine (green arrow), free CoA is released. Free CoA is necessary for continuous operation of the Krebs cycle. Moreover, stimulating PDH enhances flow through the Krebs
cycle; as a consequence, maximum oxygen capacity (the capacity for aerobic regeneration of adenosine triphosphate) is increased. Together
with a decreased respiratory quotient (the quotient of exhaled CO2 equivalents per inhaled O2), this can mean increased exercise
performance. CoA, coenzyme; CoASH, CoASH, acetyl coenzyme A; CPT, carnitine
palmi- toyltransferase; PDH, pyruvate
dehydrogenase.
The function that has been investigated most thoroughly scientifically is the carnitine-dependent transport of fatty acids
through the inner mitochondrial membrane. Other established functions of L-carnitine are the preservation of membrane integrity, the stabilization of a
physiologic coenzyme A (CoA) acetyl-CoA (coASH) ratio in mitochondria, and the
reduction of lactate pro- duction.7,8 In vitro investigations have strongly supported the notion that L-carnitine is able to inhibit apoptosis (programmed cell death)9 –11
(Figure 2).
The intracellular homeostasis of carnitine is controlled by different membrane transporters. The organic cation transporters (OCTNs), in
particular OCTN2, physiologically the most important, operate on intestinal absorption and renal
reabsorption of L-carnitine
and play a major role in tissue distribution and varia- tions in transport
rates. Inborn or acquired defects on this carnitine transport mechanism lead to
primary or secondary carnitine deficiency.
The OCTN2 mRNA
content of cells
is reduced with aging12 and by oxygen radicals.13 OCTN2 is directly inhibited by several agents and substances known
to induce systemic carnitine deficiency.
Secondary carnitine deficiency
is often seen
in patients on regular hemodialysis,14 with metabolic disorders, and in pregnancy.15
L-carnitine, widely available over the counter, is also favored
among athletes. Rumors that L-carnitine supplementation helped the Italian national soccer team to win the world championship in 1982 contributed immensely to its popularity. The most important claim relates to the
role of carnitine in fat metabolism. L-carnitine is often advertized to improve fat metabolism, reduce fat mass, and
increase muscle mass. In other words, the substance is portrayed as a “fat burner.” Therefore, carnitine is
often recommended for conditions in which weight loss is indicated.
Endurance athletes use carnitine to increase the oxidation of fat during
exercise and spare muscle glycogen. This review critically examines whether the claims associated with L-carnitine are justified.
Historically, skeletal muscle
was seen mainly as the site of lactate production during contraction, and
lactate production was associated with insufficient muscle oxygenation and consequently
fatigue. Later, it was recognized that skeletal muscles
not only play an
important role in lactate production but also in lactate clearance, and this improved understanding
has led to a renewed interest in the metabolic fate of lactate in skeletal
muscle and other tissues. Tracing studies using radioactive labeled lactate
have shown that skeletal muscle extracts lactate from the circulation despite a
substantial net lactate release, and that skeletal muscle has a large capacity
for lactate oxidation; these processes are enhanced with exercise.
ROLE OF CARNITINE IN FAT METABOLISM
L-carnitine plays an important role in fat metabolism. In the overnight-fasted state, during the resting state, and during exercise of low to moderate intensity, longchain fatty acids represent up to 80% of the energy sources. The best described function of L-carnitine is in its role as a cofactor of carnitine, acyltransferases transporting long-chain fatty acids across the mitochondrial inner membrane.21 In the absence of L-carnitine, the inner mitochondrial membrane would be impermeable to long-chain fatty acids and fatty acyl-CoA esters. Once inside the mitochondria, these compounds can be degraded to acetyl-CoA through a process known as oxidation. Carnitine also plays a decisive role in maintaining the acetyl CoA/CoA ratio in the cell. During high-intensity exercise, there is a large production of acetyl-CoA. This increase in turn inhibits the pyruvate dehydrogenase (PDH) complex and reduces flux through the PDH complex.22 As a consequence, acetyl-CoA gives rise to lactate. Acetyl-CoA reacts with free carnitine to form acetyl-carnitine and CoA.
Carnitine therefore may supress the accumulation of lactic acid, thereby enhancing high-intensity
exercise performance. This has been confirmed in several studies,
which are summarized in Table I. Results from a
pilot study in patients with the human immuno- deficiency virus receiving
nucleoside analog therapy have sug- gested that L-carnitine may be helpful
for patients who have nucleoside analog–related lactic acidosis with blood
lactate levels higher than 10 mM/L.23 Sweeney et al.24 showed that addition of L-carnitine may improve the quality of platelet concentrates that are stored beyond
5 d
by providing better
pH preservation, less glucose consumption, and less lactate generation.
