The protein you eat becomes enzymes, hormones, structural components, immune molecules, and neurotransmitters. The pathways from dietary protein to functional molecules have specific nutrient cofactor requirements at every step. When these pathways are disrupted by B6 insufficiency, gut dysfunction, or Clostridium overgrowth, the consequences appear across mood, cognition, energy, and immune function simultaneously.
Protein is the macronutrient that does the most work. Not in terms of calories — fat provides more calories per gram — but in terms of biological function. Proteins are enzymes, hormones, structural components, immune molecules, transporters, receptors, and signalling agents. The dietary protein that enters your gut as chicken breast or lentils is broken down to individual amino acids and reassembled, according to genetic instruction, into the specific proteins your body needs at that moment. What you eat, how you digest it, and how your metabolism handles the nitrogen it releases are all clinically consequential.
Transamination: The transfer of an amino group from one molecule to another, catalysed by aminotransferases (transaminases). ALT (alanine aminotransferase) and AST (aspartate aminotransferase) — the liver enzymes on every blood panel — are transamination enzymes. Elevated ALT and AST indicate hepatocyte damage because these enzymes leak from injured liver cells into the blood. All transamination reactions require pyridoxal phosphate (P5P, active B6) as a cofactor. B6 insufficiency impairs amino acid metabolism broadly.
Oxidative deamination: Removal of the amino group as ammonium (NH4+), leaving a carbon skeleton (alpha-keto acid) that enters energy metabolism. Glutamate dehydrogenase performs this reaction for glutamate, releasing ammonia and alpha-ketoglutarate (a Krebs cycle intermediate). This is why the Krebs cycle and amino acid metabolism are deeply intertwined — amino acid carbon skeletons feed directly into the cycle.
The urea cycle: Ammonia (NH3) is toxic to the brain. The liver converts ammonia to urea via the urea cycle (ornithine → citrulline → argininosuccinate → arginine → ornithine + urea). Urea is water-soluble and excreted in urine. The urea cycle requires: arginine, ornithine, citrulline (all produced in the cycle), bicarbonate (links to acid-base balance), N-acetylglutamate (NAG) as an allosteric activator, and adequate liver function. Urea cycle stress elevates orotate on the OAT — a marker of nitrogen overload or cycle impairment.
Glucogenic vs ketogenic amino acids: Amino acid carbon skeletons are classified by their metabolic fate. Glucogenic amino acids (alanine, glycine, serine, glutamine, and others) can be converted to glucose via gluconeogenesis. Ketogenic amino acids (leucine, lysine) produce acetyl-CoA or acetoacetate and cannot produce glucose. Most amino acids are both. This distinction matters in fasting and diabetes — glucogenic amino acids maintain blood glucose when carbohydrate is unavailable.
Several amino acids are direct precursors to neurotransmitters — the same molecules the Neurogistics system assesses via urinary metabolites. The pathway from dietary protein to neurotransmitter synthesis is a chain of enzymatic reactions, each with specific nutrient cofactor requirements.
Tryptophan hydroxylase (requires iron, oxygen, BH4). Aromatic amino acid decarboxylase (requires B6/P5P). BH4 is synthesised via the MTHFR pathway — MTHFR variants impair BH4 production and therefore impair serotonin synthesis independently of tryptophan availability.
Tyrosine hydroxylase (requires iron, BH4). AADC (requires B6/P5P). Dopamine → noradrenaline via dopamine beta-hydroxylase (DBH), requires copper and vitamin C. HPHPA from OAT inhibits DBH — the gut-brain dopamine connection.
Glutamate decarboxylase (GAD, requires B6/P5P as pyridoxal phosphate). GAD antibodies are present in type 1 diabetes and some neurological conditions — they impair GABA synthesis. B6 insufficiency is one of the most common contributors to low GABA and high glutamate patterns.
When tryptophan is shunted away from serotonin synthesis (by IDO enzyme, activated by inflammation), it goes through the kynurenine pathway. Quinolinate (neurotoxic, elevated in neuroinflammation) vs kynurenate (neuroprotective). Visible on OAT. B6 drives the neuroprotective branch.
Protein adequacy has two components that are frequently conflated: quantity (total grams of protein consumed) and quality (completeness of the amino acid profile and digestibility). The reference dietary intake of 0.75g protein per kg body weight is a minimum for nitrogen balance in sedentary adults, not an optimal for health, muscle maintenance, or recovery. In a meta-analysis of 49 trials in people doing resistance training, extra protein stopped adding muscle above about 1.6 g per kg of body weight a day (Morton 2018).
Protein digestibility matters because the amino acids that reach the bloodstream depend not just on what is eaten but on how well the upper GI tract digests it. Low gastric acid (hypochlorhydria), impaired pancreatic protease output (low elastase-1 on GI-MAP), and intestinal permeability all reduce effective amino acid absorption. A client eating “enough” protein but with impaired digestive function may be functionally protein-insufficient at the tissue level.
Nitrogen balance compares nitrogen intake (protein) to nitrogen excretion (urea in urine, faecal nitrogen). Positive nitrogen balance = protein synthesis exceeding breakdown = anabolism. Negative nitrogen balance = protein breakdown exceeding synthesis = muscle loss. Negative nitrogen balance occurs in: caloric restriction (gluconeogenesis consumes amino acids), infection and inflammation (acute phase response is protein-expensive), corticosteroid excess (chronic cortisol is catabolic), inadequate protein intake, and inadequate caloric intake (protein is diverted from synthesis to energy when calories are insufficient).
Amino acids are the most versatile molecules in metabolism. They build structure, carry signals, generate energy, produce neurotransmitters, support immunity, and buffer pH. When dietary protein is adequate but absorption is impaired, or when metabolic demand exceeds supply, the consequences appear across every system simultaneously — which is why fatigue, poor mood, slow recovery, hair loss, and immune dysfunction so often travel together.
Metabolomix+ OAT (amino acid panel): The most direct assessment. Measures urinary amino acids reflecting absorption, utilisation, and metabolic pathway activity. Key markers: low tryptophan (serotonin precursor depletion), low tyrosine (dopamine precursor), elevated orotate (urea cycle stress or B12 deficiency), elevated xanthurenate and kynurenate (B6 insufficiency, tryptophan pathway shunting), HPHPA (Clostridium marker disrupting dopamine pathway via DBH inhibition). Blood chemistry: Total protein and albumin (protein status over weeks to months), BUN/urea (nitrogen excretion rate — elevated suggests high protein catabolism or impaired excretion), ALT and AST (transaminase activity reflects amino acid metabolism; mild elevation may indicate B6 insufficiency before hepatocyte damage is the cause). GI-MAP: Elastase-1 (pancreatic protease output for protein digestion), SIgA (mucosal immune status affecting absorptive surface integrity), zonulin is often included, but it is a weak marker and does not measure permeability.
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