Do humans produce rennin?

Question

At school, we've been taught that human infants produce rennin/chymosin (which aids in the digestion of milk). More specifically, it is the peptic cells in the stomach which secrete prorennin, the inactive form of rennin (in addition to pepsinogen, the pepsin proenzyme).

User @another'homosapien's answer here also seems to concur with this (excellent answer by the way, I enjoyed reading it).

However

According to Mod. @AliceD's answer here (yet another excellent answer):

...in humans there is only a chymosin pseudogene present...

Which (probably?) implies that humans (infant or otherwise) do not produce rennin.

I managed to get my hands on the Textbook of Medical Physiology (Guyton and Hall, South-Asian edition), and according to the book (Chapter Gastric secretions, page 406) peptic cells produce a large quantity of pepsinogen. There is, however, no mention of prorennin. I even flipped over to the Appendix at the back to look up "Rennin", but it turns out there is absolutely no mention of rennin in the book.

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My questions,

• Some sources claim that rennin is produced in human (infants). Is this true?

• Other sources claim that rennin is not produced in humans ( we have a pseudogene for it though). Is this correct (I mean the "rennin-is-not-produced" bit, not the "pseudogene" bit)?

• If rennin is produced in humans only during infancy, what stops it from being produced as we mature? (I'm asking this because every source I've seen that claims that rennin is produced in humans, explicitly states that is done so during infancy...which would suggest that rennin is not produced in adults)

Answer 1

Scanning various reviews it seems that everyone who mentions the possibility of a human chymosin refers to a single paper. So for example this 2014 review has a single reference to a human chymosin:

Henschel et al. detected a protease in the gastric aspirates of newborn infants within 6–10 h postpartum that was not pepsin [62]. The electrophoretic mobility and immunoreactivity are similar to that of calf chymosin, a protease that cleaves κ-casein and causes casein curdling. This protease is unique in that it disappears from gastric fluid at 10 days postpartum and is not found in adult gastric fluid.

I don't have access to the Henschel et al. paper (from 1987) but here is the abstract:

The electrophoretic mobilities of proteases present in gastric juice taken within 10 h of birth from 5 healthy, premature infants were compared with calf chymosin, pig pepsin A and human adult gastric juice. The juice from 2 infants contained predominantly a chymosin-like enzyme, another had almost exclusively pepsins similar to those of the adult juice, while the other two contained a mixture of both. The pepsins consisted of two elements, probably pepsin A (EC 3.4.23.1), and pepsin C (EC 3.4.23.3). Single radial immunodiffusion gave a definite reaction to calf anti-chymosin serum in five samples taken from a further 17 infants. These results indicate that some human infants secrete chymosin. The reaction in the immunodiffusion assay indicated a much lower enzyme activity than that implied from electrophoretic separations. It is suggested that species differences resulted in poor cross-reactivity of the antiserum.

Now, obviously, without seeing the data it isn't possible to be conclusively critical, but the quality of the evidence seems to be rather weak, being based upon similar electrophoretic mobilities and an immunodiffusion assay (why not a Western blot?) with an overt apology for weak cross-reactivity of the antiserum used.

However, leaving all of that to one side, the strangest thing about this is the sporadic appearance of the proposed chymosin: although 4/5 were scored as chymosin positive in the 1st experiment, is it likely that 2 of these would apparently contain little pepsin? And in the second experiment (the immunoassay) only 5/17 scored positive for chymosin.

Evidently no-one has ever reproduced this result, and the evidence for the pseudogene (but no active gene) is very strong. I vote that humans do not produce a chymosin.

Update Having read Bryan Krause's answer: if the human gene product was lacking an exon's worth of amino acid sequence then presumably it wouldn't have an electrophoretic mobility that was closely similar to the calf protein.

Answer 2

I think the answer is really that is isn't clear, though I only searched a bit and found mostly old papers.

It seems like people have found immunoreactivity to anti-rennin antibodies in human infants, but that doesn't necessarly mean rennin is present, just something similar (which could even be a totally unrelated protein).

On the genetics side, humans have a pseudogene for rennin (known as prochymosin), but if you take the same exons from that gene that are used to make rennin in cows, the protein would be truncated because one of those exons has a frame-shift mutation (this is why they are calling it a pseudogene). However, it is possible that there is a functional protein produced by that gene if that 'exon' is excised from the transcript (see the paper below).

Örd, T., Kolmer, M., Villems, R., & Saarma, M. (1990). Structure of the human genomic region homologous to the bovine prochymosin-encoding gene. Gene, 91(2), 241-246.

Answer 3

Way back in 1964 I was asked a question about Rennin in a physiology class. Perhaps you are not searching back far enough for information. Also, if the infant was not nursing on human milk there may not be a substance present to cause rennin production, if nursing on cows milk the substance that causes the production is not the same as in human milk so no rennin is produced. If all other mammals produce rennin it would seem that humans would also produce unless after several generations no stimulation has resulted in functional loss. One assumption you can always make is the body knows what it is doing. We discover scientific facts:God creates them.