SEMUT JEPANG (TENEBRIO MOLITOR)

APAKAH SEMUT JEPANG ITU ?

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:

1. Suka atau cepat berkembangbiak
2. Hidup berkoloni atau berkelompok
3. Ruas badan lebih besar dari ruas kepala
4. Ukuran tubuh kecil hanya beberapa milimeter
5. Bukan tipe hewan pemakan daging/sesama
6. Memiliki sayap tapi tidak bisa terbang
7. Makanan ragi tape
8. Memiliki badan yang keras,
9. 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

Erick D. Aguilar-Miranda ,^† Mercedes G. López ,^‡ Clara Escamilla-Santana ,^§ and Ana P. Barba de la Rosa *^†

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.

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.

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.