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Unveiling the Hidden World Inside Us: The Intricate Dance of Diet, Metabolism, and Oxalate Production

Jan 10, 2024 | Diet, Digestive/Urinary, Evidence Based, Inflammation, Oxalate, Science-Based, Wellness

The topic of oxalate accumulation from citrate by Aspergillus Niger, and specifically the biosynthesis of oxalate from its ultimate precursor, is an area of interest in microbiology and biochemistry. Aspergillus Niger is a common species of fungus known for its industrial applications and its role in various biochemical processes. Here’s a summary based on the available resources.

Oxalate Biosynthesis

Oxalate is a simple dicarboxylic acid and in the context of Aspergillus Niger, it’s a secondary metabolite. The biosynthesis of oxalate involves enzymatic reactions where oxaloacetate, formed from citrate, is converted into oxalate. This process involves the decarboxylation of oxaloacetate to form oxalate and acetic acid or CO2, depending on the specific pathway.

Role of Citrate

Citrate, a key intermediate in the citric acid cycle, serves as the precursor for oxalate biosynthesis in Aspergillus Niger. The fungus has the ability to accumulate high levels of citrate and convert it into oxalate under certain conditions. This conversion is significant in various industrial and biotechnological applications.

The conversion of citrate to oxalate in Aspergillus Niger is catalyzed by specific enzymes. These enzymes are part of the metabolic pathways that regulate the production and accumulation of oxalate in the fungus. The regulation of these enzymes can influence the amount of oxalate produced.

Environmental Factors

The production of oxalate from citrate in Aspergillus Niger can be influenced by various environmental factors, including pH, temperature, and the availability of nutrients. Under acidic conditions, Aspergillus Niger tends to produce more oxalate.

The ability of Aspergillus Niger to produce oxalate from citrate has implications in biotechnology. Oxalate production can be harnessed for various applications, including the bioremediation of metal ions through the formation of insoluble oxalates and in the production of certain pharmaceuticals.

Understanding the mechanisms behind oxalate biosynthesis in Aspergillus Niger is valuable for both fundamental scientific research and practical applications. It can aid in the development of strategies to either enhance or inhibit oxalate production, depending on the desired outcome.

Can oxalate be formed in humans from Aspergillus via this citrate pathway?

In humans, oxalate is primarily produced as a metabolic end-product, mainly from the metabolism of vitamin C, glyoxylate, and possibly other precursors. However, the specific pathway involving Aspergillus Niger converting citrate to oxalate, as observed in fungal metabolism, does not directly occur in human physiology.

In humans, the biochemical pathways for oxalate production are different from those in fungi like Aspergillus Niger. While Aspergillus Niger can convert citrate to oxalate efficiently, human metabolism processes citrate mainly through the citric acid cycle (Krebs cycle) for energy production, without converting it to oxalate as a significant pathway.

However, it’s important to note that gut microbiota, including various bacteria, can influence oxalate metabolism in the human body. Some gut bacteria are capable of degrading oxalates, which can help in reducing the overall oxalate burden. But this bacterial degradation of oxalates in the human gut is distinct from the fungal conversion of citrate to oxalate seen in Aspergillus Niger.

While Aspergillus Niger has a unique pathway for converting citrate to oxalate, this specific pathway is not a part of human oxalate metabolism. Human oxalate production is primarily endogenous and linked to different metabolic processes compared to what is observed in fungal systems.

Aspergillus, particularly Aspergillus Niger, is known for its ability to produce oxalates in its own metabolic processes. However, the direct contribution of Aspergillus to oxalate levels in humans is a different matter and is more complex.

Humans can be exposed to Aspergillus species through various environmental sources, as these fungi are commonly found in soil, air, and decaying plant matter. While these exposures are generally harmless to healthy individuals, they can pose risks in certain situations.

In immunocompromised individuals, Aspergillus can cause infection, known as aspergillosis. This condition can lead to various health issues, but the direct contribution of Aspergillus to oxalate production in the human body through infection is not clearly established.

Endogenous Oxalate Production

In humans, oxalate is typically produced endogenously as a metabolic byproduct. This production is not directly linked to fungal activities but rather to the metabolism of certain substances like vitamin C and glyoxylate.

Gut Microbiome Interaction

The human gut microbiome, which includes a variety of bacteria, can interact with ingested oxalates, affecting their absorption and excretion. Certain gut bacteria can degrade oxalates, potentially reducing their levels in the body. However, the role of Aspergillus or its metabolites in this process is not a significant factor in human oxalate metabolism.

There is also a situation known as Enteric Hyperoxaluria which I discuss in more detail here. This is often due to fat malabsorption seen when there is leaky gut, AKA intestinal permeability and poor bile synthesis. Keep in mind, mitochondrial dysfunction can lead to this phenomenon as well, as you need ATP to make enzymes!

Dietary Oxalate Sources

Most oxalates in the human diet come from certain plant foods, not from fungal sources. The contribution of Aspergillus to dietary oxalate intake is negligible compared to direct ingestion of oxalate-rich foods.

Aspergillus and Industrial Processes: While Aspergillus Niger is used industrially for oxalate production and other biochemical processes, this does not directly influence oxalate levels in humans unless there is some form of direct and significant exposure or contamination.

Let’s delve into the details of how oxalate is produced in the human body, focusing specifically on the contributions of vitamin C and glyoxylate.

Vitamin C and Oxalate Production

Vitamin C Metabolism

Vitamin C, also known as ascorbic acid, is an essential nutrient in the human diet. It’s involved in several key physiological processes, including the synthesis of collagen, the enhancement of iron absorption, and functioning as an antioxidant.

Conversion to Oxalate

A portion of ingested vitamin C is metabolically converted to oxalate in the body. When vitamin C is broken down (metabolized), one of the byproducts is oxalate. This conversion process typically occurs in the liver and kidneys.

Factors Influencing Oxalate Production

The amount of oxalate produced from vitamin C can vary based on several factors, including the amount of vitamin C ingested. High doses of vitamin C, especially when taken as supplements, are more likely to result in increased oxalate production. However, for most people consuming vitamin C within recommended dietary allowances, this is not a significant concern.

Oxalate and Kidney Stones

The oxalate produced can combine with calcium to form calcium oxalate, which is a common type of kidney stone. Therefore, individuals who are prone to forming kidney stones, particularly calcium oxalate stones, are often advised to monitor their vitamin C intake.

Glyoxylate and Oxalate Production

Glyoxylate is an intermediary compound in the metabolism of certain amino acids and lipids. It’s a part of various metabolic pathways in the body, particularly those involving the processing of fats and proteins.

In humans, glyoxylate can be converted into oxalate. This conversion is part of the body’s normal metabolic processes and usually happens in the liver. Glyoxylate itself can be derived from the breakdown of glycine (an amino acid) or from the metabolism of hydroxyproline (found in collagen).

In certain rare genetic conditions, like primary hyperoxaluria, the body’s metabolism of glyoxylate to oxalate is abnormally increased. This leads to excessive production and accumulation of oxalate, which can form crystals and result in kidney stones or other health issues.

For most individuals, the body maintains a balance in glyoxylate and oxalate levels. Problems typically arise only in the presence of specific metabolic disorders or genetic conditions.

I talk more about this in this blog.

In conclusion, both vitamin C and glyoxylate are involved in the endogenous production of oxalate in humans. While vitamin C contributes to oxalate production as a byproduct of its metabolism, glyoxylate is converted to oxalate as part of amino acid and lipid metabolism. Understanding these pathways is crucial, especially for individuals who are prone to kidney stones or have metabolic disorders affecting oxalate production.

Can Aspergillus contribute to oxalate in humans?

Humans can be exposed to Aspergillus species through various environmental sources, as these fungi are commonly found in soil, air, and decaying plant matter. While these exposures are generally harmless to healthy individuals, they can pose risks in certain situations.

Oxalate deposition

In immunocompromised individuals, Aspergillus can cause infection, known as aspergillosis. This condition can lead to various health issues, but the direct contribution of Aspergillus to oxalate production in the human body through infection is not clearly established.

This article suggests that oxalate deposition occurred due to Aspergillus, it is likely referring to a rare and specific pathological condition. In such cases, Aspergillus infection could potentially lead to oxalate production or deposition in human tissues in the following ways:

Certain species of Aspergillus, like Aspergillus Niger, are known to produce oxalates as a part of their metabolic processes. In cases of invasive aspergillosis (a severe fungal infection that can occur in immunocompromised individuals), the fungus might produce oxalates locally in the infected tissues. This could lead to oxalate deposition in those tissues.

Secondary Effects of Infection

The body’s response to a fungal infection, including inflammatory processes, might indirectly contribute to localized oxalate deposition. For example, tissue damage and inflammatory responses could alter local metabolism and pH, potentially influencing oxalate precipitation.

Direct Deposition from the Fungus

In rare and severe cases, the fungus itself may deposit oxalates directly into the tissue as a part of its growth and metabolic activity. This is an unusual situation and typically associated with severe, unchecked infections.

Case Reports and Studies

Instances of oxalate deposition due to Aspergillus are relatively rare and are usually documented in case reports or specific clinical studies. They often occur in unique clinical scenarios, particularly in patients with compromised immune systems.

It’s important to note that such cases are exceptional and not representative of the typical interaction between Aspergillus and human oxalate metabolism. In the vast majority of situations, Aspergillus exposure or infection in humans does not lead to significant oxalate deposition.

References

Crivelli JJ, Mitchell T, Knight J, Wood KD, Assimos DG, Holmes RP, Fargue S. Contribution of Dietary Oxalate and Oxalate Precursors to Urinary Oxalate Excretion. Nutrients. 2020 Dec 28;13(1):62. doi: 10.3390/nu13010062. PMID: 33379176; PMCID: PMC7823532

Kubicek CP, Schreferl-Kunar G, Wöhrer W, Röhr M. Evidence for a cytoplasmic pathway of oxalate biosynthesis in Aspergillus niger. Appl Environ Microbiol. 1988 Mar;54(3):633-7. doi: 10.1128/aem.54.3.633-637.1988. PMID: 3132096; PMCID: PMC202517.

Müller HM. Oxalate accumulation from citrate by Aspergillus niger. I. Biosynthesis of oxalate from its ultimate precursor. Arch Microbiol. 1975 Apr 7;103(2):185-9. doi: 10.1007/BF00436348. PMID: 1156092.

Oda M, Saraya T, Wakayama M, Shibuya K, Ogawa Y, Inui T, Yokoyama E, Inoue M, Shimoyamada H, Fujiwara M, Ota T, Takizawa H, Goto H. Calcium oxalate crystal deposition in a patient with Aspergilloma due to Aspergillus niger. J Thorac Dis. 2013 Aug;5(4):E174-8. doi: 10.3978/j.issn.2072-1439.2013.08.45. PMID: 23991333; PMCID: PMC3755682.

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