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A number of enzymes can be measured in the blood or plasma that aid in the diagnosis of certain diseases. For example, patients with particular liver diseases may have elevated aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) levels in the blood. These enzymes are normally involved in biochemical reactions of metabolism that interconvert amino acids with other metabolic intermediates - that is, biochemical reactions that are common within the liver cell. Also, patients with pancreatitis frequently have elevated amylase and lipase levels, which are digestive enzymes normally secreted into the gastrointestinal tract. During pancreatitis these enzymes are released into the blood, rising and falling with the resolution of pancreatic damage/inflammation.

Pathologically, the tissues that are damaged in these diseases (liver and pancreas, respectively) are the source of the elevated enzymes. In healthy individuals, however, these same enzymes are still found in low concentrations in the circulating blood. What is the source of these enzymes that are found in low circulating concentrations? Is it still those same tissues (e.g. AST/ALT from the liver)? Is this secondary to "normal turnover" of cells within those tissues? Or, alternatively, are these enzymes secreted into the blood to serve a particular function?


For example... There is a freely available manuscript by Arnold and Rutter published in the Journal of Biological Chemistry (1963) that discusses experimental evidence for active amylase secretion from the liver during an isolated liver perfusion experiment. Amylase continues to be secreted, even in the absence of other enzymes that would otherwise indicate liver damage (suggesting that the amylase is intentionally being secreted for some unknown purpose). This is an paper from almost 60 years ago - do we know what some of these enzymes like AST/ALT and amylase do in the plasma? Or are those functions still unknown?

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These enzymes, while useful markers of disease, are not only produced during the disease state, and are not only produced in one organ. It is therefore not surprising that there are always low levels released into the biochemical milieu that is the blood. If there are not even low levels of the enzymes then that might indicate that the organ is not doing it's job properly.

I'll approach this from a veterinary viewpoint but I imagine it is much the same in humans. My preferred source for information about veterinary clinical pathology is Cornell's EClinpath site.

The major tissue sources of AST are liver, skeletal muscle, and cardiac muscle. A small amount is produced by erythrocytes. In lesser concentrations it is also found in renal epithelial cells and brain tissue. It therefore should be no surprise that low levels are found in blood. It is not difficult to picture a small amount of leakage from erythrocytes in the normal state, even without pathologic haemolysis, given the regular turnover of cells and permeability of erythrocytes – although I suspect this is a minor source. Just due to the fact that the liver's normal function is to deal with many cytotoxic compounds, even in the completely healthy patient there always is going to be some low level of hepatocellular damage. As a result, a very low serum level of AST might be indicative of a poorly functioning liver (e.g. with a chronic hepatitis).

Among veterinary species there is considerable variation in the clinical usefulness of ALT. For example, it is a very useful indicator of liver disease in dogs and cats, much less so in horses. Much like AST, ALT is also produced in liver, muscle, kidney, and erythrocytes.

Amylase is known to be produced by cells in the pancreas, salivary gland, duodenum, ileum, ovary, and testes. Of course, the pancreas produces the most of this enzyme, which is why it is somewhat clinically useful (though I can't say I like it much at least for veterinary species).

The bottom line is that these enzymes play an important role in biochemical reactions of many different tissues. While the enzymes may be produced in predominance in one tissue, they have the same function (at a biochemical level) in all these tissues (i.e. they convert the same reactions). I view it more as a difference of the tissue need for these enzymes rather than a difference in function between tissues.

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  • $\begingroup$ Harry - I guess my question bluntly is "is there any evidence that these enzymes (like AST, ALT, amylase) are intentionally secreted from healthy, non-damaged tissues? This is what is alluded to in the JBC article, but I've never heard any evidence for this in my experience. $\endgroup$ – Vance L Albaugh Jul 3 '16 at 3:15
  • $\begingroup$ @Vance I'm not sure, and I couldn't find any studies that specifically track these enzymes from their source in healthy patients. But I guess the point of my answer is that, for example, healthy functioning liver tissue might by definition of its function lead to mild hepatocellular damage and thus AST/ALT leakage. I understand this isn't a completely satisfactory answer so I hope that someone can come up with some numbers for us. $\endgroup$ – Harry Vervet Jul 3 '16 at 3:43

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