Sulfate

Sulfate, the fourth most abundant anion in human plasma, plays a crucial role in various physiological processes including xenobiotic biotransformation, steroid metabolism, and neurotransmitter regulation. 

Essential for cellular functions, sulfate aids in the sulfonation of steroids, proteins, and proteoglycans, modifying the biological activities of endogenous compounds and maintaining tissue structure. 

Sulfate is vital for fetal development, dependent on maternal supply due to limited fetal production, with defects in metabolism potentially causing developmental disorders. 

In liver detoxification, sulfotransferases use sulfate to make xenobiotics and endobiotics more hydrophilic for easier elimination. 

Sulfated steroid hormones, which serve as reservoirs for active hormones, play key roles in reproductive and endocrine functions. 

Sulfate, sourced from the metabolism of sulfur-containing amino acids like methionine and cysteine, is also a biomarker for kidney stones, helping assess urinary chemistry and renal function.

What is Sulfate?

Sulfate, the fourth most abundant anion in human plasma, is important in various physiological processes including xenobiotic biotransformation, steroid metabolism, and neurotransmitter regulation [11.].

Sulfate Roles in Human Physiology

Roles of Sulfate in Cellular and Tissue Health

Sulfate is essential for various cellular processes, including the sulfonation of steroids, proteins, and proteoglycans [5.].

Sulfonation, mediated by sulfotransferases, is critical for modifying biological activities of endogenous compounds and maintaining normal tissue structure [5., 6.]

Sulfate transport across cell membranes is facilitated by specific transporters, primarily from the SLC26 gene family [11.].

Sulfate in Fetal Development

Sulfate is essential for fetal development, with fetal tissues relying on maternal sulfate supply due to limited production capacity [5.].

Defects in sulfate metabolism can lead to various developmental disorders, particularly affecting bone and cartilage formation [5.].

Sulfate in Phase II Liver Detoxification

Sulfate is an essential compound in phase II liver detoxification through the action of sulfotransferases (SULTs). These enzymes catalyze the transfer of a sulfonate group to various substrates, including xenobiotics and endobiotics, making them more hydrophilic and easier to eliminate [16.].

Sulfated Steroid Hormones

Sulfated steroid hormones play a crucial role in reproductive processes and endocrine function. Initially considered inactive metabolites, these compounds serve as a storage reservoir for biologically active hormones [12.].

Sulfation enhances circulatory transit of hydrophobic steroids, while desulfation by steroid sulfatase (STS) activates them in target cells [13.].

Sulfated steroids are transported into cells via organic anion-transporting polypeptides [13.]. 

Estrogen sulfurylation in target tissues, such as the uterus and mammary tumors, may control the availability of 17β-estradiol to cytoplasmic receptors [3.].

The German Research Foundation established a research group to investigate the biological significance of sulfated steroid hormones in reproduction, focusing on transport, sulfation, desulfation, and effects on steroid biosynthesis and membrane receptors [9.].

Sources of Sulfate

Dietary Sulfate Sources

Sulfate is naturally produced through the metabolism of sulfur-containing amino acids such as methionine and cysteine [5., 7.].

Dietary sulfate is generally well-absorbed in the gastrointestinal tract, with absorption capacity plateauing at 5-16 mmol/day [7.].

Methionine and cysteine are amino acids obtained from dietary sources and are metabolized in the liver, releasing sulfate as a byproduct. Additionally, sulfate is produced during the breakdown of sulfated biomolecules, such as glycosaminoglycans and steroid hormones [8., 10.].

Sulfate as a Biomarker for Kidney Stones

Sulfate is an important biomarker for kidney stones due to its role in urinary chemistry and renal function. 

Urinary sulfate excretion is a key component in evaluating kidney stone patients, as it helps estimate dietary acid load and affects the saturation of calcium salts in urine [2., 4.].

Stone formers have been shown to have a significantly higher fractional excretion of sulfate compared to healthy individuals, with 80% of stone formers exhibiting fractional excretions above 0.26 [14.].

Sulfate measurement is commonly included in kidney stone panels and, when combined with other urinary parameters like pH and ammonium, provides insights into dietary stone risk, bowel disease, acidification disorders, and urinary infections [2.].

Lab Testing for Sulfate

Test Information, Sample Collection and Preparation

Sulfate as a standalone biomarker is typically tested to assess protein intake, as sulfur-containing proteins including methionine and cysteine are the primary sources of sulfate in the human body. It may also be used to help identify kidney stone risk [1., 15.].

Sulfate levels are typically assessed in urine. A spot collection or a 24 hour collection can be done. Samples can be collected from home or in a clinical setting.

It is important to consult with the ordering provider prior to sample collection, as special preparation or collection instructions may be necessary. 

Sulfated steroid hormones may also be assessed, which can be tested in blood, urine or saliva.

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