L-threonine is regulating the acid-base balance in the human body

I. Metabolic Characteristics and Acid-Base Substance Production

As an essential amino acid with a hydroxyl group, L-threonine's metabolic pathways relate to acid-base balance through unique decomposition products:

1. Hepatic Catabolic Pathway

Catalyzed by threonine dehydratase (TDH), L-threonine first converts to α-ketobutyrate, then generates acetyl-CoA via mitochondrial β-oxidation. Each molecule of threonine produces ~2 H⁺ during complete oxidation, theoretically imposing an acid load. However, its net acid production (15–20 mEq/g nitrogen) is significantly lower than sulfur-containing amino acids (≈40 mEq/g nitrogen).

2. Renal Metabolic Buffering

Proximal tubular cells convert threonine to glycine and glyoxylic acid via threonine dehydrogenase (TDH2). Glycine, as an ammonia precursor, generates NH₃ through glutaminase-mediated decomposition in the kidney. NH₃ combines with H⁺ to form NH₄⁺ for urinary excretion, exerting direct alkalinizing effects. Studies show renal threonine uptake increases by 30%–50% under acid load, enhancing ammonia production.

II. Indirect Buffering Mechanisms via Protein Synthesis

As a key component of structural proteins like collagen and mucin, L-threonine influences acid-base balance through synthesis and degradation:

1. Construction of Protein Buffering Systems

Threonine-containing proteins feature histidine residues with imidazole groups (pKa≈6.0), critical for blood buffering. For example, threonine accounts for 5%–7% of plasma albumin, whose buffering system rapidly neutralizes sudden H⁺ surges (e.g., during lactic acidosis). Threonine deficiency reduces hepatic albumin synthesis, weakening immediate blood buffering capacity.

2. Link Between Tissue Repair and Acid-Base Homeostasis

In tissues vulnerable to acid-base damage (e.g., intestinal mucosa, renal tubules), threonine is a major substrate for mucin (e.g., MUC2). The mucin layer acts as a physical barrier, reducing direct erosion by acidic substances (e.g., gastric acid, urine). Threonine deficiency decreases intestinal mucus layer thickness by 40% in mice, increasing mucosal H⁺ permeability and indirectly affecting systemic acid-base balance.

III. Synergistic Regulation with Other Amino Acids

L-threonine forms a metabolic network with glutamine, arginine, etc., in acid-base balance:

1. Renal Synergy Between Glutamine and Threonine

Glutamine decomposition in the kidney produces NH₃ and α-ketoglutarate (generating HCO₃⁻), while threonine provides precursors for glutamine synthesis via glycine. During alkalosis, renal threonine metabolism decreases to limit NH₃ production; during acidosis, both synergize to enhance ammonia excretion and HCO₃⁻ reabsorption.

2. Acid-Base Signal Interaction Between Arginine and Threonine

Nitric oxide (NO) from arginine metabolism regulates threonine transporter (e.g., B⁰AT1) expression in renal tubular epithelial cells. In metabolic acidosis models, NO promotes tubular threonine uptake via PI3K-AKT signaling, enhancing NH₄⁺ production. This interaction endows threonine’s acid-base regulation with dynamic adaptability.

IV. Compensatory Regulation in Pathological States

L-threonine exhibits specific regulatory roles in acid-base imbalance-related diseases:

1. Protective Mechanisms in Chronic Kidney Disease (CKD)

CKD patients often suffer metabolic acidosis due to reduced glomerular filtration and renal acid excretion. Threonine compensates via:

Enhancing renal tubular glutaminase activity to increase NH₄⁺ production (20%–30% above normal);

Serving as an energy substrate to maintain tubular epithelial function and improve HCO₃⁻ reabsorption. Clinical studies show threonine supplementation raises serum HCO₃⁻ by 1.5–2.0 mEq/L in CKD patients, reducing acidosis incidence.

2. Metabolic Intervention in Diabetic Ketoacidosis (DKA)

During DKA, massive ketone body (β-hydroxybutyrate, acetoacetate) production causes H⁺ overload. Threonine contributes to correction by:

Feeding acetyl-CoA into the TCA cycle to reduce ketone precursor (e.g., acetoacetate) availability;

Promoting skeletal muscle ketone utilization to lower blood ketoacid concentration. Animal experiments show threonine supplementation decreases blood ketone levels by 25%–30% in DKA models, accelerating acid-base balance recovery.

V. Clinical Correlations Between Dietary Threonine and Acid-Base Balance

Long-term dietary threonine intake influences systemic acid-base status:

1. Potential Balancing Effects of High-Protein Diets

While threonine-rich foods (dairy, eggs, lean meat) impose some acid load, threonine-mediated protein synthesis and renal ammonia metabolism partially offset this effect. Healthy individuals consuming 1.2 g/kg threonine daily (1.5× the normal recommendation) exhibit 15%–20% higher urinary NH₄⁺ excretion and maintain serum HCO₃⁻ at the upper normal range.

2. Risks of Acid-Base Imbalance in Threonine Deficiency

Vegetarians or patients with malabsorption are prone to relative threonine deficiency, potentially leading to:

Reduced hepatic albumin synthesis, weakening blood buffering;

Decreased renal ammonia production, increasing metabolic acidosis risk. Epidemiological data show individuals with threonine intake <50% of the recommendation have serum HCO₃⁻ 1–2 mEq/L lower and urinary pH 0.3–0.5 units lower than normal populations.

L-threonine regulates human acid-base balance through multi-dimensional mechanisms: dynamic equilibrium of acid-base production, construction of protein buffering systems, renal ammonia metabolism synergy, and pathological compensation. Its core role lies in its dual nature as a hydroxyl-containing amino acid: decomposing to produce acids while promoting renal ammonia generation and tissue repair for alkalinization. This bidirectional regulation makes it a vital amino acid for maintaining acid-base homeostasis. Clinically, rational threonine supplementation (especially in CKD, DKA, etc.) may assist in improving acid-base imbalance by enhancing renal acid excretion and tissue buffering, though specific dosages and intervention timings require more evidence from evidence-based medicine.