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Reference Guide
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3-Phenylpropionylglycine
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3-Phenylpropionylglycine

3-Phenylpropionylglycine (PPG) is a medium-chain acyl glycine compound formed by the conjugation of phenylpropionic acid with glycine, with the chemical formula C11H13NO3.  

While typically a minor metabolite of fatty acids, elevated urinary excretion of PPG can indicate certain metabolic disorders, such as medium-chain acyl-CoA dehydrogenase deficiency.

PPG is also a metabolite produced by gut microbiota, which significantly influence host metabolism.  For example, studies have shown that PPG has potential anti-adipogenic effects. 

It suppresses lipid droplet accumulation during adipocyte differentiation by down-regulating lipogenic genes and affecting the peroxisome proliferator-activated receptor (PPAR) signaling pathway. 

This makes PPG a promising candidate for developing anti-obesity and metabolism-modulating drugs.

Laboratory testing for PPG typically involves urine samples, with lower levels generally recommended. Elevated levels of PPG can be indicative of metabolic disorders, and treatments like riboflavin and MCT oil may help regulate its levels.

What is 3-Phenylpropionylglycine?  [3.] 

3-Phenylpropionylglycine is an medium-chain acyl glycine compound with the chemical formula C11H13NO3. It is a metabolite formed from the conjugation of phenylpropionic acid with glycine.

Acyl glycines are normally minor metabolites of fatty acids.  However, the excretion of certain acyl glycines, including 3-phenylpropionylglycine, can be elevated in certain metabolic disorders.  

For example, urinary excretion of 3-phenylpropionylglycine is a diagnostic marker for medium-chain acyl-CoA dehydrogenase deficiency, a relatively common deficiency.  

3-phenylpropionylglycine is a metabolite produced by various microbes that can generate phenylpropionic acid, the precursor of 3-phenylpropionylglycine.  [1.] 

3-Phenylpropionylglycine (PPG) as an Anti-Adipogenic Agent  [4.] 

Gut microbiota produce various metabolites that significantly influence host metabolism, offering potential resources for developing anti-obesity and metabolism-modulating drugs.  One such metabolite, 3-phenylpropionylglycine (PPG), a glycine conjugate of bacteria-derived 3-phenylpropionic acid (PPA), has shown promise in this regard.

In a study examining PPG's anti-adipogenic effects, researchers evaluated its impact on preadipocyte-to-adipocyte differentiation using 3T3-L1 cell models.  

PPG was found to suppress lipid droplet accumulation during differentiation by down-regulating lipogenic genes such as acetyl CoA carboxylase 1 (Acc1) and fatty acid synthase (Fasn).  Unlike similar compounds, such as cinnamoylglycine and hippuric acid, PPG specifically inhibited lipid accumulation. 

Transcriptomic analyses revealed that PPG down-regulated adipogenesis and metabolism-related genes, particularly affecting the peroxisome proliferator-activated receptor (PPAR) signaling pathway.  

This suppression is associated with adiponectin as a key gene in the network of differentially expressed genes. 

Thus, PPG inhibits adipocyte differentiation by targeting the adiponectin-PPAR pathway, highlighting its potential as a bacteria-derived metabolite with anti-adipogenic effects.

Laboratory Testing for 3-Phenylpropionylglycine

Lab Test Information, Sample Collection and Preparation

Typically, urine samples are collected for 3-Phenylpropionylglycine testing.  It is important to consult with the ordering provider regarding preparation prior to sample collection, as certain supplements or medications may alter test results.  

Interpretation of 3-Phenylpropionylglycine Results

Optimal Levels of 3-Phenylpropionylglycine Results

Generally, lower levels of compounds such as 3-phenylpropionylglycine are recommended.  

For reference, one lab recommends levels of 3-phenylpropionylglycine of: < 1.3

nmol/mg Creatinine  [6.] 

Clinical Significance of Elevated Levels of 3-Phenylpropionylglycine

Medium-chain acyl-CoA dehydrogenase deficiency (MCAD) is a common dehydrogenase deficiency that causes an elevation in 3-phenylpropionylglycine levels.  

Riboflavin and MCT oil may help regulate levels of 3-Phenylpropionylglycine.  [2.] 

Clinical Significance of Low Levels of 3-Phenylpropionylglycine

Low levels of 3-phenylpropionylglycine are not considered clinically significant.  

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3-Phenylpropionylglycine
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See References

[1.] Bhala A, Bennett MJ, McGowan KL, Hale DE. Limitations of 3-phenylpropionylglycine in early screening for medium-chain acyl-coenzyme A dehydrogenase deficiency. J Pediatr. 1993 Jan;122(1):100-3. doi: 10.1016/s0022-3476(05)83499-7. PMID: 8419594.

[2.] Document: OMX Quick Reference Guide | Diagnostic Solutions Laboratory. www.diagnosticsolutionslab.com. Accessed May 29, 2024. https://www.diagnosticsolutionslab.com/document/omx-quick-reference-guide

[3.] Human Metabolome Database: Showing metabocard for 3-Phenylpropionylglycine (HMDB0002042). hmdb.ca. Accessed May 29, 2024. https://hmdb.ca/metabolites/HMDB0002042

[4.] Jung HR, Oh Y, Jang D, Shin S, Lee SJ, Kim J, Lee SE, Oh J, Jang G, Kwon O, Lee Y, Lee HY, Cho SY. Gut bacteria-derived 3-phenylpropionylglycine mitigates adipocyte differentiation of 3T3-L1 cells by inhibiting adiponectin-PPAR pathway. Genes Genomics. 2023 Jan;45(1):71-81. doi: 10.1007/s13258-022-01332-y. Epub 2022 Nov 24. PMID: 36434390.

[5.] PubChem. Phenylpropionylglycine. pubchem.ncbi.nlm.nih.gov. Accessed May 29, 2024. https://pubchem.ncbi.nlm.nih.gov/compound/Phenylpropionylglycine

[6.] Rupa Health.  OMX - Urine + Plasma Sample Report.pdf. Google Docs. Accessed May 29, 2024. https://drive.google.com/file/d/1NWreSzJjfxdBXEi_D2ZjqEaEO1K_GeM2/view

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