You eat well, train smart, and still feel wiped after a long fast or a hard workout. What if a tiny molecule in your urine could reveal how well your mitochondria are handling the load? The Tiglylglycine (TG) test does exactly that. It turns a whisper of amino acid metabolism into a measurable signal you can track. Not a hype metric. A real biochemical breadcrumb that follows isoleucine catabolism and fatty acid oxidation in real time.
What This Test Actually Measures
Plain-English definition
The Tiglylglycine test measures a specific acylglycine in urine that forms when your body conjugates tiglyl-CoA with glycine. Tiglyl-CoA is an intermediate in the breakdown of the essential amino acid isoleucine. When mitochondrial enzymes are stressed or partially blocked, more tiglyl-CoA gets diverted into tiglylglycine and excreted. Translation: higher TG often signals a bottleneck in isoleucine catabolism or broader mitochondrial beta-oxidation strain.
How it gets into the body
You do not “take in” tiglylglycine from the environment. You make it. During normal protein turnover and after protein-rich meals, isoleucine is broken down in mitochondria. One step creates tiglyl-CoA. If that intermediate cannot efficiently proceed to the next energy-producing steps, your liver uses glycine N-acyltransferase to couple tiglyl-CoA to glycine. The resulting tiglylglycine is water soluble and exits in urine. Periods of fasting, illness, or intense endurance training can push more substrate through this pathway and reveal hidden inefficiencies.
What sample you’ll provide
This test uses urine, typically a first-morning sample corrected to creatinine to account for dilution. Because acylglycines turn over quickly, a spot urine sample reflects recent metabolic status over the previous day or so rather than long-term exposure.
How the Test Works
Collection and timing
Collection is simple: you provide a clean-catch urine sample. First-morning collections are common to reduce variability from daytime hydration and activity. Keeping your routine consistent before each test helps you see signal over noise. Big swings in fasting duration, extreme workouts, or unusual diets can shift acylglycine levels and make apples-to-apples comparisons harder.
Laboratories quantify tiglylglycine using mass spectrometry, most often liquid chromatography–tandem mass spectrometry for high specificity and low detection limits. Internal standards help separate TG from look-alike molecules and control for extraction recovery. Some labs use gas chromatography–mass spectrometry after derivatization; the aim is the same: precise separation, accurate quantification.
What the number represents
Results are typically reported as a concentration indexed to urine creatinine, such as micromoles per mole creatinine. The number reflects the amount of tiglylglycine excreted over a short window, often 24 to 48 hours. High values suggest increased diversion of tiglyl-CoA into glycine conjugation and point to metabolic conditions that favor that detour.
What the Results Mean
Reference intervals vs. personal context
Population reference intervals anchor interpretation, but they are not one-size-fits-all. Age matters because newborns and infants often have higher acylglycine outputs as their mitochondria mature. Hydration changes apparent concentration. Recent fasting, fever, or prolonged exercise can transiently elevate acylglycines. A value above your lab’s upper reference limit flags a signal worth contextualizing with symptoms, diet, and complementary labs. A single elevated TG does not diagnose a disease; it indicates a metabolic pattern that merits a closer look.
Pattern recognition
TG rarely speaks alone. When tiglylglycine rises alongside specific acylglycines or acylcarnitines, the pattern points toward the pathway under strain. Pairing TG with C5:1 acylcarnitine can highlight an isoleucine step. Broad elevations in multiple acylglycines, plus dicarboxylic acids in urine organic acids, can suggest generalized fatty acid oxidation stress. A cluster that includes 3-methylcrotonylglycine pushes attention toward leucine metabolism, while increases in suberylglycine hint at medium-chain fatty acid flux. Pattern, not just magnitude, is the story.
Follow-up testing
Because tiglylglycine is a pathway marker, it is often interpreted with a plasma acylcarnitine profile, urine organic acids, and basic chemistries like glucose, ketones, and liver enzymes. In select cases, clinicians use genetic testing to evaluate enzymes involved in isoleucine catabolism or electron transfer flavoprotein function. Riboflavin status can be relevant because several mitochondrial dehydrogenases depend on FAD, derived from vitamin B2. The goal is to connect the TG signal to the right mechanism, then track it over time for trend confirmation.
Key Systems Affected
Nervous system
Mitochondria power neurons. When beta-oxidation and branched-chain amino acid pathways falter, the brain feels it. Energy shortfalls can present as fatigue, brain fog, or slow recovery after catabolic stress. In more severe inborn errors, infants or children might experience hypoketotic hypoglycemia or developmental concerns during catabolic episodes. For most adults, TG is a subtle clue linking “why am I so drained after a long fast?” to mitochondrial workload.
Liver and detox pathways
The liver is home base for glycine conjugation. When tiglyl-CoA accumulates, hepatic glycine N-acyltransferase ramps up conjugation to tiglylglycine. That demand can nudge glycine pools and intersect with other conjugation pathways. Oxidative stress markers sometimes drift when mitochondrial flux is off, and mild transaminase bumps can appear during systemic stress. TG tells you where the load is coming from: an upstream isoleucine intermediate getting rerouted.
Kidneys and filtration
Tiglylglycine is excreted by the kidneys, so renal function influences what you measure. Creatinine indexing helps normalize for dilution, but significant kidney impairment can lower measured excretion even when production is high. Hydration alters apparent concentration. That is why stable collection conditions boost interpretability.
Endocrine and metabolism
Hormonal states steer substrate choice. During fasting, low insulin and higher glucagon increase fatty acid oxidation and amino acid catabolism. Endurance training shifts the mix further. Those states can transiently elevate acylglycines, including TG, without any pathology. Carnitine availability also modulates acyl flux, and riboflavin status shapes the activity of FAD-dependent dehydrogenases central to these pathways.
Common Sources of Exposure
Environmental and household
There is no environmental “exposure” to tiglylglycine itself. What elevates TG are physiological conditions that increase isoleucine breakdown or reveal mitochondrial bottlenecks. Think prolonged fasting, intercurrent illness, high-volume endurance efforts, or rapid weight-loss phases that upshift beta-oxidation. In those contexts, TG serves as a readout of how well your system keeps the assembly line moving.
Dietary and occupational
Protein-rich meals increase isoleucine flux. Ketogenic or very low-carb patterns boost reliance on fatty acid oxidation, which can uncover hidden inefficiencies and nudge acylglycines upward. Most people process these shifts smoothly. If TG rises disproportionately to context, that is the useful signal. There is no known occupational source of TG because it is an endogenous compound.
Clues from history
Helpful prompts include recent fasting duration, illness or fever, big swings in training load, and diet changes like starting a ketogenic phase. In infants and children, feeding difficulties, lethargy with illness, or newborn screening flags add important context. In adults, unexplained fatigue during fasts or long runs, or slow recovery after viral infections, can align with transient TG elevations.
Detoxification and Elimination
Physiology 101
Primary clearance is conjugation plus renal excretion. When tiglyl-CoA accumulates, the liver attaches glycine to form tiglylglycine, which is then filtered by the kidneys and released in urine. The process unfolds over hours to days, so your result mirrors recent metabolic conditions rather than months of history. Remove the push, and the signal typically fades quickly.
Systems that support clearance
Several systems determine how much tiglyl-CoA needs conjugation. Mitochondrial enzymes in the isoleucine pathway move the intermediate forward. Electron transfer flavoprotein and its dehydrogenase shuttle electrons to the respiratory chain. Adequate riboflavin supports FAD-dependent steps. Glycine pools enable conjugation when detours occur. Renal filtration completes the exit.
Why responses vary
Genetics influence enzyme efficiency in the isoleucine pathway and in electron transfer, explaining why some people generate more TG under the same stress. Nutrient status, especially riboflavin and carnitine, shifts capacity. Age matters because neonatal mitochondria are still calibrating. Co-exposures like intercurrent illness, fever, or caloric deficit change substrate flow and reveal latent bottlenecks that are invisible at rest.
Biomarker Correlations
Functional context from broader labs
Acylcarnitine profiles add sharp resolution. A rise in C5:1 acylcarnitine alongside tiglylglycine strengthens the isoleucine link. Organic acid testing can show companion dicarboxylic acids during fatty acid oxidation strain. Basic labs like glucose, ketones, lactate, and liver enzymes help frame whether the TG signal coincides with systemic stress or is an isolated blip.
Nutrient cofactors and capacity
Riboflavin status is a quiet lever here because FAD sits inside several dehydrogenases that move substrates past the tiglyl-CoA step. Carnitine supports shuttling of acyl groups into mitochondria and buffers overflow as acylcarnitines. Glycine availability affects conjugation options. Coenzyme Q10 connects downstream in the electron transport chain. Together, these cofactors describe the runway length for clean substrate oxidation.
Interpreting together
When tiglylglycine rises in parallel with a compatible acylcarnitine signature and organic acid pattern, the story edges toward a pathway bottleneck rather than a lab quirk. If TG is modestly elevated but glucose, ketones, and clinical context point to a recent fast or a marathon training block, a transient physiologic bump is more likely. Trend plus pattern is how you separate strain from signal.
Optimal vs. Normal
Population ranges
Reference ranges reflect typical values in a broad population. For many healthy adults, tiglylglycine is low to undetectable at baseline. Infants can show higher values during metabolic maturation. Different labs use different methods and cutoffs, so ranges are not interchangeable across reports.
Longevity-oriented targets
Clinicians focused on metabolic resilience often aim for a stable, low TG signal outside periods of catabolic stress. The idea is simple: the less diversion into glycine conjugation under everyday conditions, the smoother the mitochondrial flow. There is no universal “optimal” number, but a personal baseline that sits comfortably within your lab’s reference interval and stays steady over time is reassuring.
Trend over time
Direction tells the tale. A single high datapoint is a weather snapshot. Serial results are climate. If TG drops after a febrile illness resolves or stabilizes after your training taper, the system is responsive. If it drifts upward without an obvious trigger, expanding the evaluation with companion biomarkers adds clarity. Nonlinear responses are common at low concentrations; small absolute changes can mark meaningful shifts because the baseline is near zero.
Why Testing Is Worth It
From mystery to measurement
Fatigue after fasting or long workouts can feel vague. The TG test converts that feeling into a measurable pathway readout. It maps how your mitochondria handle isoleucine intermediates under load and whether they need frequent detours. That is actionable biochemistry, not a vibe.
Guiding remediation
Results help prioritize where to look next. A transient bump that tracks with a known stressor points to normal physiology under strain. A persistent elevation with compatible acylcarnitine and organic acid patterns narrows attention to specific steps in mitochondrial metabolism. That clarity directs whether to focus on substrate context, cofactor capacity, or deeper evaluation of beta-oxidation pathways.
Prevention and baseline
A personal baseline is powerful. It makes future changes obvious and lets you see how life events, from marathon training cycles to intermittent fasting experiments, influence your mitochondrial workload. Early detection of atypical patterns can cue timely follow-up before symptoms escalate.
From Lab Values to Next Steps with Superpower
Tiglylglycine is a small molecule with a big message: how your mitochondria handle isoleucine and fatty acid flux when life gets demanding. Interpreted alongside acylcarnitines, organic acids, and core chemistries, it tells a coherent story about energy pathways, nutrient cofactors, and stress responsiveness. Connect the dots and you convert a single number into a map you can track over time.
Want the full picture? Pair your TG result with Superpower’s 100+ biomarker panel to see exposure, metabolism, and recovery in one view—then watch how your system adapts across training blocks, fasts, and everyday life.
