Blood urea nitrogen and usage of proteins?

Question

I have been reading some books and am getting slightly confused. Here is roughly what I have read.

The greater the blood urea nitrogen the greater the usage of proteins (since blood urea nitrogen is created via the metabolism of proteins).

and

A positive nitrogen balance (where nitrogen balance $=$ N intake $-$ N loss) indicates a greater usage of proteins.

To me these two seem to be contradictory, if you have greater blood urea nitrogen then surly you will have more nitrogen lost meaning the nitrogen balance would be more negative. So do these two statements contradict and either way please can you explain.

Answer 1

The quotes in the question provide incomplete information at best.

Let's focus on the nitrogen (N) that comes from protein, ignoring for now how metabolism differs among amino acids. We'll assume for simplicity that liver function is OK so that the urea N production rate is a reasonable measure of protein N degradation rate (say in units like moles of N per hour).

First, consider simple conservation of mass:

Intake = Loss + Net Storage

If you think about this in terms of protein N from the perspective of the whole body, you start to see the limitations in those quotes.

First, loss from the whole body of metabolized protein N in the form of urea N mostly occurs via the urine. Impaired kidney function may lead to less urea being excreted than is being formed. You will then have "Net Storage" of urea N in the blood and body fluids, so BUN can rise even if metabolism of protein is unchanged. In fact, BUN tests can be used with other tests to provide information about kidney function. Thus BUN levels don't necessarily tell you much about the urea N production rate or protein degradation rate.

Second, you have to consider that one "use" of proteins can be "Net Storage" to build muscle mass. That type of "use" won't show up in increased urea N production. Alternatively, body protein in muscle can be broken down to be "used" for metabolism/catabolism during an overnight fast, possibly leading to increased urea N production rate depending on how the mix of protein, fat, and carbohydrate catabolism has changed. Furthermore, the effects on BUN levels will depend on kidney function.

Both storage and degradation/catabolism are important "uses" of protein N, but they have different implications for production of urea N, and BUN levels don't necessarily represent the urea production rate.

Answer 2

The thing to remember is that no living system is 100% efficient. Firstly lets deal with your statement here:

A positive nitrogen balance (where nitrogen balance = N intake − N loss) indicates a greater usage of proteins.

Basically means what it says on the tin. If your body is utilising more nitrogen then it is giving out:

Positive nitrogen balance is associated with periods of growth, hypothyroidism, tissue repair, and pregnancy. This means that the intake of nitrogen into the body is greater than the loss of nitrogen from the body, so there is an increase in the total body pool of protein.

Now we really cant measure notrogen on a weighing scale. So the blood urea level is used as an estimator for nitrogen metabolism.

Now, as mentioned below, no system is 100% efficient, and the purpose of urea is infact to be as a vehicle to excrete toxic ammonia. Sure the body looses a few nitrogens in the form of urea, but as a whole, it gains a lot more from the metabolism.

An analogy:

In other words, think of it like this: When you make something out of wood (proteins), you get wood shavings (ammonia). Now you cant reconstitute the wood shavings back to a full wood (proteins), nor can you use wood shavings (ammonia) as they are toxic for you. So you group up the wood shavings (urea) and get rid of it.

The formula is essentially:

The number of furniture made = Function of (Weight of wood delivered - weight of saw dust taken out)

If you use a lot of wood (proteins), and are a good craftsman (healthy human) you'll ultimately have a bit more shavings (blood urea nitrogen), but a lot more furniture to move around. Now since you cant see the furniture (proteins in tissues), but you can see the shavings coming out (blood urea nitrogen) there will be a rise in the BUN.

Now if you are a poor carpenter (disease or something), you mess up and you end up wasting a lot more wood as shavings than getting the furniture right. So for say 10 kilos of wood, you can only make one couch and 9 kilos of saw dust.. you are really not doing it right, and this is where the BUN gets in the negative territory (I know 10-9 is not negative, but remember the body has a baseline need of say 6 couches and you are only giving it 1, the body will get that from somewhere to the detriment if your health)

Apologies for the long winded analogy. I hope you understood what I was trying to imply. I am pretty sure someone out there will give a more scientifically accurate answer, so you might want to wait on that also.

Further reading from the wiki:

Amino acids from ingested food that are not used for the synthesis of proteins and other biological substances — or produced from catabolism of muscle protein — are oxidized by the body, yielding urea and carbon dioxide, as an alternative source of energy.

The oxidation pathway starts with the removal of the amino group by a transaminase; the amino group is then fed into the urea cycle. The first step in the conversion of amino acids from protein into metabolic waste in the liver is removal of the alpha-amino nitrogen, which results in ammonia. Because ammonia is toxic, it is excreted immediately by fish, converted into uric acid by birds, and converted into urea by mammals.

Ammonia (NH3) is a common byproduct of the metabolism of nitrogenous compounds. Ammonia is smaller, more volatile and more mobile than urea. If allowed to accumulate, ammonia would raise the pH in cells to toxic levels. Therefore many organisms convert ammonia to urea, even though this synthesis has a net energy cost. Being practically neutral and highly soluble in water, urea is a safe vehicle for the body to transport and excrete excess nitrogen.

Answer 3

Urea is the major nitrogenous end product of protein metabolism, and its production reflects both the dietary intake of protein as well as the protein catabolic rate. The magnitude of these processes have a similar influence on urea concentration in the blood stream. Please note, that BUN, aka blood urea nitrogen is a misnomer, here plasma or serum urea nitrogen is meant and not the urea concentration in the red blood cells.

Urea biosynthesis from ammonia is carried out exclusively by liver via urea cycle. As explained above, dietary protein intake as well as the protein catabolism end up with a certain amount of ammonia which converted to urea in the liver. This is why, the higher the protein intake, the higher the urea concentration; the more protein disintegrated via catabolism, the higher the urea concentration. The excretion of urea is carried out mostly by kidneys in a certain (almost constant) rate.

Now, the positive nitrogen balance means that in the system there is an increase of “net storage” of nitrogen (and we deal with azotemia). The important point is - the urea metabolism is a continuous event where two processes are going in almost (but not absolute) parallel: the urea production (liver) and urea excretion (kidneys). There is a constant “delay” between the urea production and urea excretion and if the organism is in high protein intake and/or high protein catabolism rate this delay will bigger. On the other hand, the bigger the excessive amount of urea, the more urea is excreted until its concentration is normalized. If the urea production will decrease (normal protein intake, normal metabolism), the system will eventually excrete the excessive amount of urea and nitrogen balance will be around zero value (never will be absolute zero though). So, if the blood sample from an otherwise healthy individual is taken in the middle of the explained cycle (higher protein intake/catabolism), there will be a positive nitrogen balance.

As can be seen from the explanation (I hope that it can), there is no contradictions between the clauses in the question.