Branched-Chain Amino Acids Can Predict Mortality in ICU Sepsis Patients

Sepsis biomarkers and potential therapeutic targets are urgently needed. With proton nuclear magnetic resonance (1H NMR) spectroscopy, several metabolites can be assessed simultaneously. Fifty-three adult medical ICU sepsis patients and 25 ICU controls without sepsis were prospectively enrolled. 1H NMR differences between groups and associations with 28-day and ICU mortality were investigated. In multivariate metabolomic analyses, we found separate clustering of ICU controls and sepsis patients, as well as septic shock survivors and non-survivors. Lipoproteins were significantly different between sepsis and control patients. Levels of the branched-chain amino acids (BCAA) valine (median 43.3 [29.0–53.7] vs. 64.3 [47.7–72.3] normalized signal intensity units; p = 0.005), leucine (57.0 [38.4–71.0] vs. 73.0 [54.3–86.3]; p = 0.034) and isoleucine (15.2 [10.9–21.6] vs. 17.9 [16.1–24.4]; p = 0.048) were lower in patients with septic shock compared to those without. Similarly, BCAA were lower in ICU non-survivors compared to survivors, and BCAA were good discriminators for ICU and 28-day mortality. In uni- and multivariable logistic regression analyses, higher BCAA levels were associated with decreased ICU- and 28-day mortality. In conclusion, metabolomics using 1H NMR spectroscopy showed encouraging potential for personalized medicine in sepsis. BCAA was significantly lower in sepsis non-survivors and may be used as early biomarkers for outcome prediction.

Download Full-text

Aromatic amino acids play a harmonizing role in prostate cancer: A metabolomics-based cross-sectional study

International Journal of Reproductive BioMedicine ◽

10.18502/ijrm.v19i8.9622 ◽

2021 ◽

pp. 741-750

Author(s):

Ziba Akbari ◽

Roghayeh Taghipour Dijojin ◽

Zahra Zamani ◽

Reza Haji Hosseini ◽

Mohammad Arjmand

Keyword(s):

Prostate Cancer ◽

Amino Acids ◽

Nmr Spectroscopy ◽

1H Nmr ◽

1H Nmr Spectroscopy ◽

Aromatic Amino Acids ◽

Proton Nuclear Magnetic Resonance ◽

Least Squares Regression ◽

Cross Sectional ◽

Metabolomics Data

Background: Prostate cancer (PCa) is a common health problem worldwide. The rate of this disease is likely to grow by 2021. PCa is a heterogeneous disorder, and various biochemical factors contribute to the development of this disease. The metabolome is the complete set of metabolites in a cell or biological sample and represents the downstream end product of the omics. Hence, to model PCa by computational systems biology, a preliminary metabolomics-based study was used to compare the metabolome profile pattern between healthy and PCa men. Objective: This study was carried out to highlight energy metabolism modification and assist the prognosis and treatment of disease with unique biomarkers. Materials and Methods: In this cross-sectional research, 26 men diagnosed with stage-III PCa and 26 healthy men with normal PSA levels were enrolled. Urine was analyzed with proton nuclear magnetic resonance (1H-NMR) spectroscopy, accompanied by the MetaboAnalyst web-based platform tool for metabolomics data analysis. Partial least squares regression discriminant analysis was applied to clarify the separation between the two groups. Outliers were documented and metabolites determined, followed by identifying biochemical pathways. Results: Our findings reveal that modifications in aromatic amino acid metabolism and some of their metabolites have a high potential for use as urinary PCa biomarkers. Tryptophan metabolism (p < 0.001), tyrosine metabolism (p < 0.001), phenylalanine, tyrosine and tryptophan biosynthesis (p < 0.001), phenylalanine metabolism (p = 0.01), ubiquinone and other terpenoid-quinone biosynthesis (p = 0.19), nitrogen metabolism (p = 0.21), and thiamine metabolism (p = 0.41) with Q2 (0.198) and R2 (0.583) were significantly altered. Conclusion: The discriminated metabolites and their pathways play an essential role in PCa causes and harmony. Key words: Metabolomics, Prostate cancer, Aromatic amino acids, 1H-NMR spectroscopy.

Download Full-text

Discrimination of Enantiomers of Amides with Two Stereogenic Centers Enabled by Chiral Bisthiourea Derivatives Using 1H NMR Spectroscopy

Organic & Biomolecular Chemistry ◽

10.1039/d1ob00742d ◽

2021 ◽

Author(s):

Hanchang Zhang ◽

Hongmei Zhao ◽

Jie Wen ◽

Zhanbin Zhang ◽

Pericles Stavropoulos ◽

...

Keyword(s):

Amino Acids ◽

Nmr Spectroscopy ◽

1H Nmr ◽

1H Nmr Spectroscopy ◽

Chiral Recognition ◽

Stereogenic Centers

Enantiomers of a few new amides containing two stereogenic centers have been derived from D- and L-α-amino acids as guests for chiral recognition by 1H NMR spectroscopy. A variety of...

Download Full-text

Use of high-resolution proton nuclear magnetic resonance spectroscopy for rapid multi-component analysis of urine.

Clinical Chemistry ◽

10.1093/clinchem/30.3.426 ◽

1984 ◽

Vol 30 (3) ◽

pp. 426-432 ◽

Cited By ~ 204

Author(s):

J R Bales ◽

D P Higham ◽

I Howe ◽

J K Nicholson ◽

P J Sadler

Keyword(s):

Nuclear Magnetic Resonance ◽

Nmr Spectroscopy ◽

Magnetic Resonance ◽

High Resolution ◽

1H Nmr ◽

1H Nmr Spectroscopy ◽

Proton Nuclear Magnetic Resonance ◽

Resonance Spectroscopy ◽

Simple Method ◽

Nuclear Magnetic

Abstract Numerous low-Mr metabolites--including creatinine, citrate, hippurate, glucose, ketone bodies, and various amino acids--have been identified in 400- and 500-MHz proton nuclear magnetic resonance (1H NMR) spectra of intact human urine. The presence of many of these was related to the specific condition of the donors: humans in different physiological states (resting, fasting, or post-exercise) and pathological conditions (e.g., diabetes mellitus, cadmium-induced renal dysfunction). We have also monitored the metabolism of simple nonendogenous compounds (methanol and ethanol) and of acetaminophen. The pH-dependencies of the NMR chemical shifts of some urine components are reported. Our studies show that high-resolution 1H NMR spectroscopy provides a fast, simple method for "fingerprint" identification of urinary compounds. In some cases, analytes can be quantified by standard additions or by comparing integrated peak areas for the metabolites with those for creatinine. Determinations of creatinine by 1H NMR spectroscopy compared well with those by an independent chemical assay based on the Jaffé reaction.

Download Full-text

ChemInform Abstract: pH Dependence of the Stability of Boric Acid and Borate Esters of Amino Acids and Amino Diols in Aqueous Medium as Studied by 11B and 1H NMR Spectroscopy.

ChemInform ◽

10.1002/chin.198937076 ◽

1989 ◽

Vol 20 (37) ◽

Author(s):

J. VAN HAVEREN ◽

J. A. PETERS ◽

J. G. BATELAAN ◽

A. P. G. KIEBOOM ◽

H. VAN BEKKUM

Keyword(s):

Amino Acids ◽

Nmr Spectroscopy ◽

Boric Acid ◽

Aqueous Medium ◽

1H Nmr ◽

1H Nmr Spectroscopy ◽

Ph Dependence ◽

Borate Esters ◽

The Stability

Download Full-text

The First Application of 1H NMR Spectroscopy for the Assessment of the Authenticity of Perfumes

10.20944/preprints201908.0145.v1 ◽

2019 ◽

Author(s):

Grzegorz Ciepielowski ◽

Barbara Pacholczyk-Sienicka ◽

Łukasz Albrecht

Keyword(s):

Nmr Spectroscopy ◽

1H Nmr ◽

1H Nmr Spectroscopy ◽

Negative Impact ◽

Poor Quality ◽

Proton Nuclear Magnetic Resonance ◽

Resonance Spectroscopy ◽

Simple Method ◽

Counterfeit Goods ◽

Safety Issues

The industry of the counterfeit goods is one of the largest underground business in the world and it is rapidly growing. Counterfeits can lead not only to loss of profit for honest producers but also have a negative impact on consumers who receive poor quality goods at an excessive price and may be exposed to health damages and safety issues. Perfume industry is constantly exposed to the problem of counterfeits with the fast developing parallel market of inspired perfumes being an important issue. It prompts for the identification of methods that classify the quality of this type of products. In this paper the application of proton nuclear magnetic resonance spectroscopy is employed for the authentication of perfumery products for the first time. Molecular composition of several types of authentic brand fragrances for women were compared with their cheaper inspired equivalents and fake products. Our approach offers the prospect of a fast and simple method for discrimination and counterfeit detection of perfumes using 1H NMR spectroscopy.

Download Full-text

Uptake of tyrosine and leucine in vivo by brain of diabetic and control rats

AJP Cell Physiology ◽

10.1152/ajpcell.1984.247.5.c450 ◽

1984 ◽

Vol 247 (5) ◽

pp. C450-C453 ◽

Cited By ~ 20

Author(s):

J. T. Brosnan ◽

R. G. Forsey ◽

M. E. Brosnan

Keyword(s):

Amino Acids ◽

Branched Chain Amino Acids ◽

Diabetic Rats ◽

Injection Technique ◽

Brain Uptake ◽

Absolute Increase ◽

Normal Plasma ◽

Branched Chain ◽

And Control

The uptake of tyrosine and leucine by brain of control and diabetic rats was examined using the Oldendorf intracarotid injection technique. The brain uptake indexes (BUI) for tyrosine and leucine were identical in diabetic and control rats when the injectate consisted of labeled amino acids in Krebs saline. When the injectate consisted of radioactive amino acids added to plasma from either normal or diabetic rats, there was a decreased BUI for tyrosine from diabetic plasma compared with that from normal plasma. This was evident in both control and diabetic rats. Fractional uptake of leucine was unchanged in all situations. Because leucine level is elevated in plasma of diabetic rats there is an absolute increase in leucine uptake in diabetes. Branched-chain amino acids, added to normal plasma in the concentrations at which they occur in diabetic plasma, inhibited the uptake of tyrosine to the same extent as diabetic plasma did. We conclude that the decreased brain uptake and decreased brain level of tyrosine in diabetes is due to the high circulating levels of branched-chain amino acids and cannot be attributed to intrinsic changes in the blood-brain transporter for large neutral amino acids or to changes in other constituents of plasma.

Download Full-text

1H-NMR Metabolomics Identifies Significant Changes in Metabolism over Time in a Porcine Model of Severe Burn and Smoke Inhalation

Metabolites ◽

10.3390/metabo9070142 ◽

2019 ◽

Vol 9 (7) ◽

pp. 142

Author(s):

Cole Hendrickson ◽

Katharina Linden ◽

Stefan Kreyer ◽

Gregory Beilman ◽

Vittorio Scaravilli ◽

...

Keyword(s):

Nmr Spectroscopy ◽

1H Nmr ◽

1H Nmr Spectroscopy ◽

Porcine Model ◽

Burn Injury ◽

Smoke Inhalation ◽

Proton Nuclear Magnetic Resonance ◽

Severe Burn ◽

Concentration Changes ◽

Over Time

Burn injury initiates a hypermetabolic response leading to muscle catabolism and organ dysfunction but has not been well-characterized by high-throughput metabolomics. We examined changes in metabolism over the first 72 h post-burn using proton nuclear magnetic resonance (1H-NMR) spectroscopy and serum from a porcine model of severe burn injury. We sought to quantify the changes in metabolism that occur over time in response to severe burn and smoke inhalation in this preliminary study. Fifteen pigs received 40% total body surface area (TBSA) burns with additional pine bark smoke inhalation. Arterial blood was drawn at baseline (pre-burn) and every 24 h until 72 h post-injury or death. The aqueous portion of each serum sample was analyzed using 1H-NMR spectroscopy and metabolite concentrations were used for principal component analysis (PCA). Thirty-eight metabolites were quantified in 39 samples. Of these, 31 showed significant concentration changes over time (p < 0.05). PCA revealed clustering of samples by time point on a 2D scores plot. The first 48 h post-burn were characterized by high concentrations of histamine, alanine, phenylalanine, and tyrosine. Later timepoints were characterized by rising concentrations of 2-hydroxybutyrate, 3-hydroxybutyrate, acetoacetate, and isovalerate. No significant differences in metabolism related to mortality were observed. Our work highlights the accumulation of organic acids resulting from fatty acid catabolism and oxidative stress. Further studies will be required to relate accumulation of the four organic carboxylates identified in this analysis to outcomes from burn injury.

Download Full-text