Creatinine VS Creatine

Bottom Line:

CreaTINE is converted in the body to phosphocreatine which is used to make ATP in high energy requiring tissues like the brain and skeletal muscle. CreaTININE is the breakdown product of creatine and is used as a biomarker of kidney function.

Memory Aids:

CreaTINE turns into creaTININE.



Anyone who has done any amount of internal medicine has probably heard of creatinine. And anyone who is involved in athletics has probably heard of creatine. It turns out that these are very closely related molecules and that could be a good or bad thing in terms of remembering them depending on how you look at it.

The gist of the story is this. High intensity exercise or high energy requiring tissues (skeletal muscle, the brain) can quickly deplete local stores of ATP. The body needs a “reservoir” molecule that can sit around and store energy near the site of use to allow quick regeneration of ATP in the case it is needed. Now how do our molecules of the day fit into that story?

Creatine is synthesized in the liver (and kidneys) from the amino acids glycine and arginine (with some help from methionine). It can also be ingested in the form of athletic supplements (I can’t tell you how pleased I am to include a reference to an excellent review article on here). It travels from the source to skeletal muscles, the brain, heart, eyes (retina), and smooth muscle via the blood (these tissues have active transporters to grab it).  Inside the target tissues it is converted to phosphocreatine by the creatine kinase enzyme in a process that consumes 1 ATP. Now you might say, “I thought creatine was supposed to increase ATP levels, not lower them”, and you would be right. The issue here is location.

There are creatine kinase molecules found in the mitochondria of these tissues and they use the ATP produced in the mitochondria to create a whackload of phosphocreatine. This phosphocreatine is ferried outside the mitochondria, into the cytosol, and dumped next to some cellular machinery that will shortly be requiring lots of ATP. If we use the example of skeletal muscle, the phosphocreatine might be dumped next to some actin and myosin filaments. When intense exercise starts, the actin and myosin quickly consume all the available ATP floating nearby, but luckily there are some creatine kinase enzymes floating nearby too. These are different creatine kinase molecules than the ones found in the mitochondria. They catalyze the conversion of phosphocreatine and ADP back into ATP and regular old creatine again. The ATP is used by the muscle while the creatine wanders back to the mitochondria where it gets converted back into phosphocreatine by the creatine kinase in there. So the benefit here is that during “down time” the mitochondria can pump out these phosphocreatine molecules and park them by the energy consumers in the cell. Phosphocreatine is presumably more stable and safe to have around than making a bunch of ATP and trying to keep it around.

Now creatine is metabolized at a steady rate into creatinine via a spontaneous, non-enzymatic dehydration reaction. The general rate I found is about 2% of body creatine is converted to creatinine daily. Creatinine is filtered freely through the glomerulus (there is apparently some direct excretion in the distal tubule too). The important point is that there is no reabsorption. So since it is freely filtered and not reabsorbed, it reflects the glomerular filtration rate and hence renal function. Males produce on average 20-25 mg/kg/day, females about 15-20 mg/kg/day. Of course heavily muscled people have more muscle and can store more creatine, therefore they produce more creatinine. Emaciated, cachectic, or just plain small patients have less muscle and might produce smaller amounts. Lab Tests Online reports the reference ranges for creatinine production as: male 80 – 115 µmol/L (0.9 – 1.3 mg/dL) and female 53 – 97 µmol/L (0.6 – 1.1 mg/dL).


This is a Physiology Reviews article which is enormous, but contains all the information you could possibly want to know on the subject.

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