The degradation of tryptophan (TRP) along the kynurenine pathway plays a crucial role as a neuro- and immunomodulatory mechanism in response to inflammatory stimuli, such as lipopolysaccharides (LPS). In endotoxemia or sepsis, an enhanced activation of the rate-limiting enzyme indoleamine 2,3-dioxygenase (IDO) is associated with a higher mortality risk. It is assumed that IDO induced immunosuppressive effects provoke the development of a protracted compensatory hypoinflammatory phase up to a complete paralysis of the immune system, which is characterized by an endotoxin tolerance. However, the role of IDO activation in the development of life-threatening immunoparalysis is still poorly understood. Recent reports described the impact of inflammatory IDO activation and aryl hydrocarbon receptor- (AhR-) mediated pathways on the development of LPS tolerance and immune escape of cancer cells. These immunosuppressive mechanisms offer new insights for a better understanding of the development of cellular dysfunctions in immunoparalysis. This review provides a comprehensive update of significant biological functions of TRP metabolites along the kynurenine pathway and the complex regulation of LPS-induced IDO activation. In addition, the review focuses on the role of IDO-AhR-mediated immunosuppressive pathways in endotoxin tolerance and carcinogenesis revealing the significance of enhanced IDO activity for the establishment of life-threatening immunoparalysis in sepsis.

Elisa Wirthgen

Andreas Hoeflich

Endotoxin-Induced Tryptophan Degradation along the Kynurenine Pathway: The Role of Indolamine 2,3-Dioxygenase and Aryl Hydrocarbon Receptor-Mediated Immunosuppressive Effects in Endotoxin Tolerance and Cancer and Its Implications for Immunoparalysis

<i>Background</i>. Limited data exist regarding endothelin-1 (ET-1), a vasoactive contributor in vascular tone, in a population subjected to early vascular deterioration. We compared ET-1 levels and explored its association with markers of arterial stiffness in black and white South Africans.<i> Methodology</i>. This cross-sectional substudy included 195 black (men: <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2063904pt" id="M1" height="8.55521pt" version="1.1" viewBox="-0.0498162 -8.34882 34.1002 8.55521" width="34.1002pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-111" d="M495 86L479 114C446 82 419 66 409 66C401 66 401 72 406 97C420 166 436 231 453 297C489 435 454 448 428 448C406 448 384 439 354 422C305 394 222 327 161 247H159L183 345C200 415 194 448 173 448C143 448 82 410 23 351L38 325C64 349 95 371 105 371C111 371 116 365 109 336L25 -4L31 -12C50 -4 77 3 107 9C119 69 132 122 145 168C197 254 321 381 370 381C387 381 393 374 378 305L329 95C309 17 320 -12 345 -12C372 -12 430 19 495 86Z"/></g><g transform="matrix(.013,0,0,-0.013,10.158,0)"><path id="g117-34" d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"/></g><g transform="matrix(.013,0,0,-0.013,21.421,0)"><path id="g113-58" d="M244 635C114 635 38 519 38 422C38 317 111 240 217 240C236 240 255 244 277 256L345 292C311 140 203 39 59 15L64 -15C89 -15 150 -5 204 17C339 72 440 202 440 386C440 521 368 635 244 635ZM228 602C326 602 352 479 352 390C352 370 351 347 348 324C327 308 293 296 258 296C174 296 124 369 124 458C124 517 152 602 228 602Z"/></g><g transform="matrix(.013,0,0,-0.013,27.662,0)"><use xlink:href="#g113-58"/></g></svg>; women: <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2063904pt" id="M2" height="8.55521pt" version="1.1" viewBox="-0.0498162 -8.34882 34.1002 8.55521" width="34.1002pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-111"/></g><g transform="matrix(.013,0,0,-0.013,10.158,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.013,0,0,-0.013,21.421,0)"><use xlink:href="#g113-58"/></g><g transform="matrix(.013,0,0,-0.013,27.662,0)"><path id="g113-54" d="M153 550H386L412 615L406 623H120L82 318C104 327 142 338 184 338C294 338 347 275 347 187C347 112 305 39 221 39C160 39 119 71 97 89C88 97 80 96 71 90C59 80 50 67 49 57C48 45 52 36 66 23C80 9 123 -12 169 -12C221 -11 288 15 342 59C403 109 431 165 431 225C431 308 366 395 238 395C212 395 165 379 127 364L153 550Z"/></g></svg>) and 197 white (men: <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2063904pt" id="M3" height="8.55521pt" version="1.1" viewBox="-0.0498162 -8.34882 34.1002 8.55521" width="34.1002pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-111"/></g><g transform="matrix(.013,0,0,-0.013,10.158,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.013,0,0,-0.013,21.421,0)"><use xlink:href="#g113-58"/></g><g transform="matrix(.013,0,0,-0.013,27.662,0)"><use xlink:href="#g113-58"/></g></svg>; women: <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2063904pt" id="M4" height="8.55521pt" version="1.1" viewBox="-0.0498162 -8.34882 34.1002 8.55521" width="34.1002pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-111"/></g><g transform="matrix(.013,0,0,-0.013,10.158,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.013,0,0,-0.013,21.421,0)"><use xlink:href="#g113-58"/></g><g transform="matrix(.013,0,0,-0.013,27.662,0)"><path id="g113-57" d="M249 635C141 635 70 555 70 471C70 401 114 353 179 316C143 294 106 267 90 252C68 231 45 202 45 157C45 50 130 -12 237 -12C322 -12 435 52 435 169C435 256 372 304 303 343C349 374 375 398 383 407C401 429 411 458 411 487C411 569 344 635 249 635ZM238 603C285 603 337 567 337 482C337 422 310 385 276 358C205 393 145 426 145 500C145 552 179 603 238 603ZM248 20C183 20 125 70 125 163C125 218 158 268 206 300C284 261 355 217 355 143C355 66 308 20 248 20Z"/></g></svg>) South Africans. Serum ET-1 levels were measured as well as markers of arterial stiffness (blood pressure, pulse wave velocity, and arterial compliance). ET-1 levels were higher in black men and white women compared to their counterparts after adjusting for C-reactive protein. In both single and partial (adjusting for body mass index and gamma glutamyl transferase) regression analyses ET-1 correlated with age, interleukin-6, high density lipoprotein cholesterol, systolic blood pressure, pulse pressure, and pulse wave velocity in black women. In multivariate regression analyses the independent association of ET-1 with systolic blood pressure (Adj. <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2063999pt" id="M5" height="11.7978pt" version="1.1" viewBox="-0.0498162 -11.5914 49.9162 11.7978" width="49.9162pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-83" d="M610 18C585 26 567 34 540 68C517 97 499 128 476 171C452 215 425 276 413 304C496 332 570 394 570 494C570 555 545 595 509 619S419 650 364 650H139L133 622C216 615 219 612 203 527L129 132C112 40 105 36 23 28L17 0H279L285 28C199 34 194 40 211 132L239 284H284C320 284 334 275 351 236C374 182 394 140 420 93C459 23 495 -1 592 -8H600L610 18ZM480 485C480 424 449 372 403 342C374 323 338 316 293 316H245L291 562C296 589 301 601 311 608S337 618 358 618C432 618 480 575 480 485Z"/></g><g transform="matrix(.0091,0,0,-0.0091,8.151,-5.741)"><path id="g50-51" d="M414 144C384 79 371 75 317 75H135L276 221C367 316 408 376 408 465C408 570 327 635 237 635C179 635 131 609 100 575L42 494L67 471C94 510 138 565 205 565C277 565 321 517 321 435C321 348 258 270 195 195C146 137 88 81 33 26V0H411C423 44 433 88 446 135L414 144Z"/></g><g transform="matrix(.013,0,0,-0.013,16.73,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.013,0,0,-0.013,27.992,0)"><path id="g113-49" d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"/></g><g transform="matrix(.013,0,0,-0.013,34.232,0)"><path id="g113-47" d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"/></g><g transform="matrix(.013,0,0,-0.013,37.196,0)"><path id="g113-50" d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"/></g><g transform="matrix(.013,0,0,-0.013,43.436,0)"><path id="g113-52" d="M285 378C315 398 338 416 353 432C373 451 384 474 384 503C384 579 325 635 236 635H235C182 635 136 610 108 579L65 516L85 496C110 533 150 575 205 575C258 575 300 543 300 481C300 407 232 369 141 339L147 310C163 315 188 321 211 321C268 321 338 284 338 192C338 94 288 40 217 40C160 40 119 68 93 91C85 98 77 97 69 91C60 84 47 71 46 58C44 46 48 35 62 22C75 10 116 -12 162 -12C234 -12 424 62 424 224C424 297 373 359 285 376V378Z"/></g></svg>; <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42947pt" id="M6" height="12.7178pt" version="1.1" viewBox="-0.0498162 -9.28833 44.3696 12.7178" width="44.3696pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-224" d="M558 587C558 666 497 712 432 712C379 712 330 691 284 650C212 586 178 508 148 348L71 -65C49 -185 35 -229 23 -235L27 -261C49 -259 101 -251 124 -224C131 -216 138 -178 159 -24C171 66 197 200 227 356C264 550 295 668 393 668C443 668 479 632 479 575C479 516 446 458 383 418C361 404 344 398 318 397L296 350C395 338 460 281 460 192C460 110 411 40 300 40C258 40 215 55 192 69L181 51C191 18 222 -16 266 -16C308 -16 351 1 397 26C471 67 545 142 545 221C545 315 486 365 401 395C469 437 558 498 558 587Z"/></g><g transform="matrix(.013,0,0,-0.013,11.186,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.013,0,0,-0.013,22.449,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.689,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.653,0)"><path id="g113-51" d="M412 140C382 77 369 73 315 73H129L270 222C362 320 402 379 402 466C402 571 322 635 234 635C177 635 130 609 99 576L42 495L64 475C90 514 133 568 201 568C274 568 318 519 318 435C318 349 255 267 193 193C144 135 87 78 32 23V0H405C417 45 427 89 440 131L412 140Z"/></g><g transform="matrix(.013,0,0,-0.013,37.893,0)"><use xlink:href="#g113-57"/></g></svg>, <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42938pt" id="M7" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 44.5261 11.7782" width="44.5261pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-113" d="M570 304C570 398 525 448 414 448C385 448 343 445 312 434L329 511L321 518C297 504 262 482 244 460L233 411C195 397 159 381 128 358L135 332C160 347 189 360 224 373L111 -147C97 -210 84 -218 17 -231L13 -257L254 -247L259 -218L233 -216C183 -212 177 -202 189 -142L218 -1C238 -10 266 -12 283 -12C351 3 429 48 483 105C543 168 570 242 570 304ZM482 289C482 161 380 33 304 33C278 33 248 51 233 69L303 396C326 400 352 403 369 403C428 403 482 380 482 289Z"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><path id="g117-91" d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"/></g><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-50"/></g></svg>) and pulse pressure (Adj. <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2063999pt" id="M8" height="11.7978pt" version="1.1" viewBox="-0.0498162 -11.5914 49.9162 11.7978" width="49.9162pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-83"/></g><g transform="matrix(.0091,0,0,-0.0091,8.151,-5.741)"><use xlink:href="#g50-51"/></g><g transform="matrix(.013,0,0,-0.013,16.73,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.013,0,0,-0.013,27.992,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,34.232,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,37.196,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.013,0,0,-0.013,43.436,0)"><use xlink:href="#g113-50"/></g></svg>; <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42947pt" id="M9" height="12.7178pt" version="1.1" viewBox="-0.0498162 -9.28833 44.3696 12.7178" width="44.3696pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-224"/></g><g transform="matrix(.013,0,0,-0.013,11.186,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.013,0,0,-0.013,22.449,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.689,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.653,0)"><use xlink:href="#g113-51"/></g><g transform="matrix(.013,0,0,-0.013,37.893,0)"><path id="g113-56" d="M447 623H65C61 580 56 530 47 475H76C100 541 106 550 172 550H388C308 376 196 170 91 -1L98 -12L172 -2C268 204 360 408 455 611L447 623Z"/></g></svg>, <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42938pt" id="M10" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 44.5261 11.7782" width="44.5261pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><use xlink:href="#g117-91"/></g><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-50"/></g></svg>) was confirmed in black women only. ET-1 additionally associated with interleukin-6 in black women (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42938pt" id="M11" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 44.5261 11.7782" width="44.5261pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><use xlink:href="#g117-91"/></g><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-50"/></g></svg>).<i> Conclusion</i>. Our result suggests that ET-1 and its link with subclinical arteriosclerosis are potentially driven by low-grade inflammation as depicted by the association with interleukin-6 in the black female cohort.

Christine Susara du Plooy

Catharina Martha Cornelia Mels

Hugo Willem Huisman

Ruan Kruger

The Association of Endothelin-1 with Markers of Arterial Stiffness in Black South African Women: The SABPA Study

<i>E. coli</i> alanyl-tRNA exists as a dimer in its native form and the C-terminal coiled-coil part plays an important role in the dimerization process. The truncated N-terminal containing the first 700 amino acids (1&#x2013;700) forms a monomeric variant possessing similar aminoacylation activity like wild type. A point mutation in the C-terminal domain (G674D) also produces a monomeric variant with a fivefold reduced aminoacylation activity compared to the wild type enzyme. Urea induced denaturation of these monomeric mutants along with another alaRS variant (N461 alaRS) was studied together with the full-length enzyme  using various spectroscopic techniques such as intrinsic tryptophan fluorescence, 1-anilino-8-naphthalene-sulfonic acid binding, near- and far-UV circular dichroism, and analytical ultracentrifugation. Aminoacylation activity assay after refolding from denatured state revealed that the monomeric mutants studied here were unable to regain their activity, whereas the dimeric full-length alaRS gets back similar activity as the native enzyme.  This study indicates that dimerization is one of the key regulatory factors that is important in the proper folding and stability of <i>E. coli</i> alaRS.

Baisakhi Banerjee

Rajat Banerjee

Urea Unfolding Study of <i>E. coli</i> Alanyl-tRNA Synthetase and Its Monomeric Variants Proves the Role of C-Terminal Domain in Stability

Yeast can use a wide variety of nitrogen compounds. However, the ability to synthesize enzymes and permeases for catabolism of poor nitrogen sources is limited in the presence of a rich one. This general mechanism of transcriptional control is called nitrogen catabolite repression. Poor nitrogen sources, such as leucine, <i>&#x3b3;</i>-aminobutyric acid (GABA), and allantoin, enable growth after the synthesis of pathway-specific catabolic enzymes and permeases. This synthesis occurs only under conditions of nitrogen limitation and in the presence of a pathway-specific signal. In this work we studied the temporal order in the induction of <i>AGP1, BAP2, UGA4</i>, and <i>DAL7</i>, genes that are involved in the catabolism and use of leucine, GABA, and allantoin, three poor nitrogen sources. We found that when these amino acids are available, cells will express <i>AGP1</i> and <i>BAP2</i> in the first place, then <i>DAL7</i>, and at last <i>UGA4</i>. Dal81, a general positive regulator of genes involved in nitrogen utilization related to the metabolisms of GABA, leucine, and allantoin, plays a central role in this coordinated regulation.

Marcos D. Palavecino

Susana R. Correa-Garc&#xed;a

Mariana Berm&#xfa;dez-Moretti

Genes of Different Catabolic Pathways Are Coordinately Regulated by Dal81 in <i>Saccharomyces cerevisiae</i>

The catabolism of the 20 amino acids by <i>Thermoanaerobacter</i> strain AK90 (KR007667) was investigated under three different conditions: as single amino acids without an electron-scavenging system, in the presence of thiosulfate, and in coculture with a hydrogenotrophic methanogen. The strain degraded only serine without an alternative electron acceptor but degraded 11 amino acids (alanine, cysteine, isoleucine, leucine, lysine, methionine, phenylalanine, serine, threonine, tyrosine, and valine) under both of the electron-scavenging systems investigated. Acetate was the dominant end product from alanine, cysteine, lysine, serine, and threonine under electron-scavenging conditions. The branched-chain amino acids, isoleucine, leucine, and valine, were degraded to their corresponding fatty acids under methanogenic conditions and to a mixture of their corresponding fatty acids and alcohols in the presence of thiosulfate. The partial pressure of hydrogen seems to be of importance for the branched-chain alcohol formation. This was suggested by low but detectable hydrogen concentrations at the end of cultivation on the branched-chain amino acid in the presence of thiosulfate but not when cocultured with the methanogen. A more detailed examination of the role of thiosulfate as an electron acceptor was performed with <i>Thermoanaerobacter ethanolicus</i> (DSM 2246) and <i>Thermoanaerobacter brockii</i> (DSM 1457).

Sean Michael Scully

Johann Orlygsson

Amino Acid Metabolism of <i>Thermoanaerobacter</i> Strain AK90: The Role of Electron-Scavenging Systems in End Product Formation

The release of preloaded [<sup>3</sup>H]taurine from hippocampal slices from developing 7-day-old and young adult 3-month-old mice was studied in a superfusion system in the absence of glucose. These hypoglycemic conditions enhanced the release at both ages, the effect being markedly greater in developing mice. A depolarizing K<sup>+</sup> concentration accentuated the release, which indicates that it was partially mediated by exocytosis. The anion channel blockers were inhibitory, witnessing the contribution of ion channels. NO-generating agents fomented the release as a sign of the participation of excitatory amino acid receptors. The other second messenger systems were apparently less efficient. The much greater taurine release could be a reason for the well-known greater tolerance of developing nervous tissue to lack of glucose.

Simo S. Oja

Pirjo Saransaari

Properties of Taurine Release in Glucose-Free Media in Hippocampal Slices from Developing and Adult Mice

The addition of carbohydrate (CHO) in the form of simple sugars to creatine (Cr) supplements is central. The study aimed to determine whether ingestion of glucose (Glu) simultaneously with Cr and glycerol (Cr/Gly) supplement is detrimental to plasma lipids of endurance-trained individuals and find out whether modification arising can be attenuated by replacing part of the Glu with alpha lipoic acid (Ala). Twenty-two endurance-trained cyclists were randomized to receive Cr/Gly/Glu (11.4&#x2009;g Cr-H<sub>2</sub>O, 1&#x2009;g Gly/kg BM, and 150&#x2009;g Glu) or Cr/Gly/Glu/Ala (11.4&#x2009;g Cr-H<sub>2</sub>O, 1&#x2009;g Gly/kg BM, 100&#x2009;g Glu, and 1&#x2009;g Ala) for 7 days. Fasting concentration of TAG increased significantly (<i>P</i> &#x3c; 0.01) after supplementation with Cr/Gly/Glu (before: 0.9 &#xb1; 0.2&#x2009;mmol/L; after: 1.3 &#xb1; 0.4&#x2009;mmol/L) and Cr/Gly/Glu/Ala (before: 0.8 &#xb1; 0.2&#x2009;mmol/L; after: 1.2 &#xb1; 0.5&#x2009;mmol/L) but changes were not different between the groups. Supplementation significantly (<i>P</i> &#x3c; 0.05) increased the TAG to HDL-cholesterol ratio but had no effect on fasting concentration of total, HDL-, and LDL-cholesterol and insulin resistance. Thus, addition of Glu to Cr containing supplements enhances plasma TAG concentration and the TAG to HDL-cholesterol ratio and this enhancement cannot be attenuated by partial replacement of Glu with Ala.

Thelma P. Polyviou

Yannis P. Pitsiladis

Carlos Celis-Morales

Benjamin Brown

John R. Speakman

Dalia Malkova

The Effects of Hyperhydrating Supplements Containing Creatine and Glucose on Plasma Lipids and Insulin Sensitivity in Endurance-Trained Athletes

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Journal of Amino Acids