What is the Urea Cycle?
The urea cycle (also known as the ornithine cycle) is a cycle of biochemical reactions occurring in the cells of the liver that produces urea ((NH2)2CO) from ammonia (NH3) in the removal of waste nitrogen.
What is a Urea Cycle Disorder?
Urea cycle disorders (UCDs) are a group of inborn errors of metabolism affecting the detoxification of nitrogen.
WOW, what does all that mean to us with UCD’s?
Urea and proteins contain nitrogen. Protein is a chief source of nitrogen, it’s in the food we eat as protein. It’s also in our bodies. We are made up of protein (muscle, hair, skin, organs and tissues). Protein is made up of amino acids. Each amino acid (building block of protein) contains a special end group (chemical make-up) called an amine group (NH2, N is nitrogen and H2 is 2 hydrogens). Amino acids would not be amino acids without them. Nitrogen is found in our DNA and RNA, so nitrogen is throughout our bodies and in the food we eat as protein. Our bodies metabolize nitrogen constantly (from the food we eat, and even our own tissue when we are sick). There is a balance of nitrogen going on in our bodies constantly without us being aware of it. Ammonia, Urea, Uric Acid are all nitrogen wastes that the body excretes.
Understanding Nitrogen Balance
Nitrogen balance is a state in which the rate of nitrogen ingestion (what we eat) equals the rate of excretion. Growing children exhibit a state of positive nitrogen balance because they ingest more than they excrete because they retain protein for tissue growth. Pregnant women and athletes in resistance training also show positive nitrogen balance. When excretion exceeds ingestion, a person is in negative nitrogen balance. This indicates that body proteins are being broken down and used as fuel instead of from food when we don’t eat properly. In other words, when we don’t intake enough protein and/or are sick, our bodies can even use its own tissue to supply what it needs. Proteins of the muscle and liver are more easily broken down than others, so that means that negative nitrogen balance tends to be associated with muscle atrophy (muscle weakness, appearance of muscles getting smaller). When we get sick it is vital to remain hydrated and nourished. Sometimes, when we get sick, we tend to not want to eat and even the insufficient intake (like when we eat some but not enough) of carbs and fats, it can cause us to be in negative nitrogen balance (our bodies using and breaking down its own proteins). This is what we must avoid. That is why UCD patients MUST be diligent in sticking to their diet prescribed by their dietician and/or physician.
Here is some interesting news for UCD patients, carbohydrates and fats are known to have a protein-sparing effect. That means if you eat enough carbs and fats, your body will break these down for energy first. This is why when UCD patients become sick it is advised to push the soda (non-caffeine) and even some candy, because this is a quick source of carbohydrates, so that our bodies don’t get into negative nitrogen balance.
Medicines to be Avoided
Remember, glucocorticoids promote protein catabolism (breakdown) and as a result put you into a state of negative nitrogen balance (UCD patients must be careful if in negative nitrogen balance, it can happen when we are sick with flu, cold, etc. this can cause elevated ammonia levels). Glucocorticoids are a class of steroid hormones that stop inflammation. These are a HUGE concern for UCD patients. Corticosteroids, anti-inflammatories (steroidal based) are not to be used by UCD patients, however, there are times that their use can not be avoided, such as during an allergic reaction. In these instances the risk vs. benefit must be weighed carefully. Be sure to make your doctor aware of this information, AND there are certain epilepsy meds that should be avoided as well. We are all trying to prevent protein overload as UCD patients. Our successful nitrogen balance requires us to be proactive and aware of what types of food and medicine we intake so that we can be the most successful in our individual battles.
I hope that has helped you. These are the things that we can do something about like diet, protein intake, carb, and fat intake, glucocorticoid (corticosteroids) avoidance, and medicine regimen. These are all critical tools for our success.
Here is some more helpful information:
Each one of the 6 urea cycle enzymes are needed with converting ammonia nitrogen into urea nitrogen, this is a process of the urea cycle. When those enzymes are functioning properly, ammonia (one form of nitrogen) becomes urea (another form of nitrogen), and we just pee it out as urine (contains nitrogen waste). The problem having a UCD, we often don’t have enough function (if any) of our affected enzyme (depending on disorder severity) to help process that nitrogen corrrectly into the urea cycle so we can get rid of it. Ammonia nitrogen, (NH3), is unable to become urea nitrogen, (((NH2)2CO), and for those of us who can’t get rid of it, it goes throughout the blood stream until it reaches the brain.
This ammonia is toxic (toxic=poison), it causes brain damage, coma, and death. Out of control ammonia levels are ultimately what take the lives of our urea cycle disorder friends and family members.
There are ammonia scavenger drugs that help UCD patients to control these levels and without them many of us would not be here today. There are people all over the world who don’t have effective treatment or medications, too many of our friends around the world have neither one.
Patients with a complete enzyme deficiency often present during the first days of life with hyperammonemic coma ( hyper = high; ammonemic = ammonia condition) and can have high mortality despite early and aggressive treatment. The majority of survivors of a neonatal (after being born)presentation (episode) suffer from severe developmental delay and a high risk of recurrent crises. Late-onset patients may present at any age after the neonatal period and their risk of death is also high. Brain damage correlates with duration and severity of acute hyperammonemia, especially in neonatal patients. These conditions are rare and are caused by inherited deficiency of specific enzymes involved in the degradation of amino acids and the removal of ammonia, in urea cycle disorders , the ammonia isn’t removed in the body which can cause coma, brain damage and death.
There is no cure, but we will never stop hoping for a cure!
How many Urea Cycle Disorders are there?
There are 6 enzymes important to the urea cycle process.
The 6 are listed here. Also important to note, they are named according to the enzyme missing. Example: my daughter and I have OTC, we are missing the OTC enzyme, etc.
- Ornithine Transcarbamylase (OTC Deficiency)-OTC
- Argininosuccinic Acid Synthetase (Citrullinemia)-AS
- Arginase-AG
- Argininosuccinase Acid Lyase (argininosuccinic aciduria) or (ASA lyase)-AL
- Carbamyl Phosphate Synthetase (CPS1)-CPS1
- N-Acetylglutamate Synthetase-NAGS
There are 3 transporter defects as well, they are:
- Citrullinemia Type 2 – glutamate carrier, mitochondrial aspartate
- Dibasic amino acid carrier – lysinuric protein intolerance or hyperdibasic amino aciduria
- Mitochondrial ornithine carrier – or HHH syndrome (hyperornithinemia hyperammonemia homocitrullinemia
Be Encouraged!
We encourage you to ask as many questions as needed for you to better understand your UCD!
An oncoming hyperammonemic crisis can be unpredictable. UCD patients (not all) can have a sense of their own bodies going into a hyperammonemic state. Listen to your body and NEVER be afraid to ask questions. Ask lots of questions! The only bad question is the one you later regret not asking.
Use our “contact us” form, call, or email with your questions.
Stay informed and stay safe!
Forever hopeful,
CFUCDF