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The Urea Cycle and Reactive Oxygen Species

Terms in this set (32)

What happens to protein that is not broken down or absorbed?
Once protein is broken down to amino acids and absorbed, any that is not used for protein synthesis is "deaminated" and the carbon skeleton is used to provide carbohydrate or stored as fat
What happens during fasting? What waste does it generate?
During fasting, muscle protein is broken down to produce energy, again generating nitrogenous waste
Where is nitrogen converted to urea? Where is it recreated?
Nitrogen must be converted into urea in the LIVER to be excreted in the urine
Why are some amino acids not essential?
The reason some amino acids are not "essential" is because they can be made via "transamination"
What is transamination?
Transamination is also a process for removing nitrogen from amino acids; in this way tissues can use the carbon skeleton of the amino acid as fuel and transport the nitrogen to the liver for conversion to urea
What is PLP?
PLP is the coenzyme, pyridoxal phosphate, the active form of vitamin B6
What is the nitrogen balance in healthy adults?
Healthy adults are in nitrogen balance; the amount of nitrogen in the protein taken in is about equal with that excreted, mostly as urea
Ammonia--> urea balance
The properly functioning liver has a great capacity for forming urea; the greater the amount of ammonia produced, the greater the amount converted to urea
What do high levels of ammonia indicate?
High levels of ammonia indicate a problem with the liver; high urea the kidney
What can oxygen also be?
Although oxygen is necessary for life, it can also be toxic
Why is oxygen biracial?
Because oxygen has two single electrons in two different orbitals, both with the same spin, it is a "biradical"
Why can't the 2 electrons oxidize the bonds? What is required?
Fortunately these 2 electrons with the same spin cannot easily oxidize the bonds in organic compounds because of "spin restriction" - an enzyme is usually required
What is ROS naturally generated by?
Unfortunately, reactive oxygen species (ROS) are generated naturally by cellular processes
What are free radicals?
"Free" radicals are those that can exist independently (radicals can be made in an enzymatic reaction but are intermediates that form stable products and do not go "free")
What can free radicals do?
Free radicals can take electrons from other compounds (usually H's) and initiate chain reactions that damage substances within the cell
What does the mitochondrial electron transport chain do?
The mitochondrial electron transport chain produces ATP to run cellular processes but accidentally forms superoxide
What can generate ROS?
Ionizing radiation (from X-rays and radioactive chemicals) can generate ROS
What does cytochrome P450 do?
Cytochrome P450 enzymes metabolize drugs (and alcohol) and chemical toxins
What is the job or p450?
The job of these enzymes is to oxidize the drugs and other substrates to make them more soluble for excretion
What can radical intermediates do in these reactions?
Radical intermediates of these enzyme reactions can "escape" and become free radicals, causing cell damage
How can DNA be damaged by ROS?
DNA can be damaged by ROS due to strand breaks, or one of 20 different alterations that can lead to mutations
What can DNA repair systems do?
DNA repair systems can fix some of these alterations but if they are missed mutations accumulate
What reactive nitrogen-oxygen species? (RNOS)
These are free radicals as well and can cause damage to cellular components: DNA, cell membranes, enzymes, the electron-transport chain, etc.

No need to know the compounds, just that they are produced in the cell or can be from outside sources, and they are damaging to cells
What happens in inflammation to free radicals?
In inflammation free radicals are used to destroy invading pathogens or clean up dead cells in damaged tissues
In activated neutrophils what does the respiratory burst do?
In activated neutrophils the "respiratory burst" consumes oxygen to create the reactive substances that will kill phagocytosed bacteria

The release of these free radicals in areas of inflammation can lead to damage in surrounding tissues
Cellular defense mechanisms
Lucky for us we have an array of cellular defenses to help fight the effects of free radicals

We can also choose to consume a healthy diet with plenty of antioxidants to help with this defense

Many diseases occur or are made worse by too many of these ROS/RNOS
Endogenous antioxidants
Endogenous antioxidants such as superoxide dismutases (SOD) and catalases have different isoforms that exist in different parts of the cell
What do glutathione peroxidases do?
Glutathione (a tripeptide of glycine, cysteine, and glutamate) peroxidases function to remove peroxide formed outside of peroxisomes
What do those enzymes contain?
These enzymes contain metals such as Cu, Zn, Mn, Fe, and Se, which is one of the reason these minerals are required in the diet
What neutralizes free radicals?
Vitamins such as the fat-soluble vitamin E and the water soluble vitamin C are involved in neutralizing free radicals
What can vitamin E do?
Vitamin E can donate an electron to radicals and vitamin C can donate an electron to vitamin E to regenerate its antioxidant capacity
What do carotenoids do?
Carotenoids, derived from the diet have antioxidant properties as well
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