Urea Cycle; Synthesis of Amino Acids Flashcards
What is the byproduct of amino acid degradation in the fasting state?
Lots of Nitrogen
Where does glutamine go to get deanimated?
The liver
What liver enzymes turn glutamate to alpha-ketoglutarate?
- Reaction type?
- Glutaminase - Deanimation
- Glutamate Dehydrogenase - Deanimation
What enzyme deaminates alanine in the liver?
ALT
The amino group from what amino acid is used in the Urea Cycle?
- Alanine
* Note: this comes from deamination via ALT
What is the point of the Alanine cycle?
To convert Alanine to pyruvate for Gluconeogenesis
What tissues are nourished by glucose made in the Alanine cycle during the fasting state?
- Brain
- Red Blood Cells
What amino acid collects the amino groups that are taken from Alanine and other amino acids during the urea cycle?
Glutamate
What are the 3 key amino acids in the urea cycle?
- Glutamine
- Glutamate
- Alanine
Although NH4+ is the predominant form of ammonia following decarboxylation, why is NH3 also important?
Because it can cross membranes such as the BBB
What are some of the consequences of having too much ammonia in the blood (normal = 30-60 um)?
- Ammonia can cross the BBB (high levels are toxic)
- Alpha Ketoglutate (important in TCA) and glutamate (Neurotransmitter) are depleted as they get converted to Glutamine
**Overall it affects neurotransmitter and TCA
Where does most nitrogen disposal take place?
Urea Cycle in LIVER
Where does the Urea cycle occur?
- In mitochondria and cytoplasm
* ALL of it occurs in the liver
How many nitrogens are disposed of with each urea?
2
T or F: the urea cycle results in a net gain of energy in the cell
False, Making Urea is an Energetically Expensive process
What is the source of the first and seconds nitrogens in the urea cycle?
- Carbomoyl Phosphate
2. Aspartate
What is BUN a measure of?
The amount of Urea in the blood
When would a patient of high BUN?
Renal Failure
What does low BUN mean?
There is probably some type of deficiency
in enzyme or substrate
What is the most common urea cycle defect?
- OTC deficiency
What is the physiologic result from OTC deficiency?
- Blood ammonia levels are really high, NO detectable Citrulline, and HIGH Oroate
- Result is mental retardation
What is the treatment for OTC deficiency?
- Low-protein diet
2. Drugs that react with amino acids
What drugs react with amino acids do to help treat OTC deficiency?
- why does it work?
- Benzoic acid and phenylbutyrate
- These bind amino acids then are peed out
- New nitrogen is used to make amino acids , thus pulling it out of the blood
What are the 2 possible fates of oroate when there is an OTC deficiency?
- Could be used to make pyrimidines
2. Excreted in urine (this is how it is detected)
What enzyme is responsible for turning ammmonia into Carbamoyl Phosphate?
CPSI
How would you distinguish a CPSI deficiency from an OTC deficiency?
- The type of breakdown product
- Carbamoyl Phosphate will not be present in CPSI deficiency (oroate probably won’t be present either)
What enzyme is responsible for making citrulline?
OTC
What disease results from defective phenylalanine hydroxylase enzyme?
Phenylketoneuria (PKU)
What intermediate would be expected to be elevated in PKU?
Phenylalanine
What kind of diet would someone with PKU need?
- Diet Low in Phenylalanine and high in tyrosine
What type of coefactor is used in most aminotransferases?
PLP
What is the coefactor for Tyrosine Aminotransferase?
PLP
What disease results from deficient Tyrosine Aminotransferase?
Tyrosinemia II
What products build up in tyrosinemia II?
- Tyrosine and Phenylalanine
- That’s why you treat these patients with low tyrosine and low Phenylalanine diet
What disease results from Homogentisate Oxidase deficiency?
Alcaptonuria
What are the side effects and symptoms of alcaptonuria?
- Urine turns dark when exposed to air
2. Arthritis may develop later in life due to pigment build up
What is the precursor for Serine?
- 3-Phosphoglycerate
* THIS IS A GLYCOLYTIC INTERMEDIATE*
What is the precursor for Alanine?
Pyruvate
What is the precursor for Glycine?
Serine
T or F: The reaction of Serine —> Glycine catalyzed by Serine Hydroxymethyl Transferase is reversible
True
What coefactors are needed to convert Serine to glycine?
PLP and Tetrahydrofolate (FH4)
What is the most common purpose of FH4 (tetrahydrofolate) in enzymes?
- It moves 1 carbon groups
Where is folate obtained and what is the most common form in the body?
- Obtained from leafy vegetable, fruits, and legumes
- FH4 the fully reduced form is most common
Why does folate deficiency lead to neural tube defects?
- It inhibits DNA synthesis
What metabolic disorder results from inability to make Cysteine?
Homocysteinemia - High Homocysteine in blood
What enzyme is likely deficient in Homocysteminemia?
- Enzyme converting Homocysteine to Cystathione
- Enzyme = CBS (don’t have to know name)
What are two possible causes of Homocysteinemia?
- CBS (enzyme deficiency preventing Homocysteine –> Cystathione)
- FH4 or B12 deficiency (prevents homocysteine —> Methionine)
**Two possible causes means you can’t pinpoint the problem just by having high levels of homocysteine in the urine
T or F: homocysteine can be used as a marker of Cardiovascular Disease
True
Is Homocysteinuria observed when someone has Homocysteinemia?
NO, homocystinuria IS though
What is classical homocysteinemia?
- Results from an enzyme deficiency
How can classical homocyteinemia be differentiated from that which results from B12 or Folate insufficiency?
-would blood or urine testing be better for diagnosis?
Methionine will build up indicating B12 and FH4 are still working
- YOU HAVE TO TEST BLOOD, methionine will not show up in urine
What are two symptoms of Homocysteinemia?
- Dislocated Optic Lenses
2. Abnormal Blood Clotting - tissues have infarcts
How shoul classic homocysteinemia be treated?
- Diet Low in Met
- Oral B6 works for about 50% of people
Where does the source of Arginine in the cell come from?
The urea cycle
