Urea Cycle Flashcards
Where does toxic ammonia come from?
The breakdown of amino acids in muscles
What does the enzyme Glutamine synthetase do?
It uses 2 ATP to combine ammonia and glutamate to make Glutamine.
What does the enzyme Glutaminase do?
Cleaves glutamine to make glutamate and ammonia.
What does glutamine do?
Acts as a shuttle to transport ammonia through the blood.
What does Glutamate dehydrogenase do?
Combines ammonia with alpha-ketogluterate to make glutamate.
What does Alanine transaminase do and why?
Converts glutamate and pyruvate into alpha-ketogluterate and alanine. Glutamate cannot travel in the blood, but alanine can.
What does alanine do?
Converted from glutamate and pyruvate to transport imbedded ammonia through the blood to the liver cells.
What does the enzyme alanine transaminase do?
Converts alanine and alpha-ketogluterate back to pyruvate and glutamate in liver cell.
What does the enzyme carbamoyl phosphate synthetase 1 do?
It uses 2 ATP to combine ammonia with carbon monoxide to make carbamoyl phosphate.
What does the enzyme Ornithine transcarbamylase do?
Combines carbamoyl phosphate with ornithine to make citrulline.
What does the enzyme Ornithine translocase do?
Transports citrulline out of the mitochondria and into the cytoplasm of the liver cells.
What does the enzyme Argininosuccinate synthetase 1 do?
It uses 1 ATP to combine citrulline with aspartate to make arginiosuccinate in the cytoplasm.
What does the enzyme Arginiosuccinate lyase do?
It cleaves argininosuccinate into arginine and fumarate.
What does fumarate do?
Fumarate is used to make NADH in the citric acid cycle.
What does the enzyme Arginase do?
It activates hydrolysis in arginine to make urea and ornithine which is transported to the kidneys and mitochondria respectively.
Why is alpha-ketogluterate important?
The alpha-amino group of amino acids protects it from oxidative breakdown, so it must be removed and transferred to alpha-ketogluterate to begin their catabolism
What is transamination?
Funneling amino groups into glutamate
What is the first step in amino acid catabolism?
The transfer of the alpha-amino group from an amino acid to an alpha-ketogluterate by different types of specific aminotransferases, creating glutamate and leaving an alpha-keto acid. (Occurs for all amino acids except for lysine and threonine)
What does aspartate aminotransferase do?
Transfers amino groups from glutamate to oxaloacetate to form aspartate (Glutamate- amino groups ==> amino groups + oxaloacetate ==> aspartate)
What creates aspartate from glutamate amino groups combining with ocaloacetate?
Aspartate aminotransferases
How can you use aminotransferases to diagnose disease?
Aminotransferase enzymes are only found in the outside the cell in low levels, so if lots of them are found in the blood or the urine, then we know that there is cell damage
Why is glutamate important?
- The ammonia combines with glutamate to make glutamine, the non-toxic ammonia carrier.
- Glutamate is a substrate AND a regulator of the rate-limiting step activator N-acetylglutamate
What breaks down glutamate?
The enzyme glutamate dehydrogenase deaminates glutamate to release ammonia and alpha-ketogluterate (which is recycled into the citric acid cycle)
Describe the glucose-alanine pathway
Glycolysis in the muscles produce pyruvate from glucose. Alanine aminotransferase combines ammonia with pyruvate to form alanine which is then sent to the liver. In the liver, the alanine is converted back to pyruvate by alanine aminotransferase, which releases ammonia. The pyruvate continues to glucose production, while the ammonia is loaded into the urea cycle to be made into urea.
Why is urea important
It is a non-toxic molecule that can transport toxic ammonia from the liver, to the kidneys
What medicine can help with hyerammonemia?
Neomycin –> reduce ammonia-producing bacteria
What happens after ingestion of a protein-rich meal?
The concentration of N-acetylglutamate increases
What is the essential activator of the rate-limiting step in the urea cycle?
N-acetylglutamate synthase –> Acetyl-coa + glutamate ==> N-acetylglutamate
What is the rate-limiting step in the urea cycle?
Carbamoyl phosphate synthetase 1
What is the amino acid pool?
The total quantity of free amino acids available in the body at any given time.
What are the different diseases that come from defects in the metabolism and catabolism of amino acids?
Cystinuria, Histidinemia, Phenylketonuria, Methylmalonyl CoA mutase deficiency, Albinism, Homocystinuria, Alkaptonuria, Maple syrup urine disease, Cystathioninuria
What is transamination?
Transfer of amino groups from one molecule to another molecule
How many intermediates does the breakdown of amino acids have after you remove the alpha-amino groups
(Seven)
1. alpha-ketogluterate
2. oxaloacetate
3. pyruvate
4. fumarate
5. succinyl coenzyme A
6. acetyl coenzyme A
7. acetoacetate
What is oxidative deamination?
Removing amino groups from amino acids to break them down
What are glucogenic amino acids?
Amino acid catabolism yields intermediates of gluconeogenesis
What are ketogenic amino acids?
Amino acid catabolism yields ketone bodies or precursors.
(Cant be converted to glucose cause both carbon atoms are degraded into CO2 and the TCA/Krebs cycle)
What does it mean for amino acids to be both glucogenic and ketogenic?
Amino acid catabolism yields intermediates of both gluconeogenesis and ketone bodies
What does the TCA cycle do?
It removes electrons from acetyl CoA and uses the electrons to form NADPH and FADH2
What happens in oxidative phosphorylation?
Electrons released in the reoxidation of NADH and FADH2 flow through the electron transport chain to generate a proton gradient across the membrane so the protons flow through ATP synthase to generate ATP from ADP and inorganic phosphate
What are single carbon units? (slide 8)
What is tetrahydrofolate (THF)?
An active form of folate (vitamin B9 or folacin)
Can carry methyl (-CH3), methylene (-CH2-), formyl (-CH=O), formimino (-CH=NH), methenyl (-CH=)
Serine Hydroxymethyltransferase will combine Glycine and N5,N10-Methylenetetrahydrofolate to make Serine and a byproduct of Tetrahydrofolate
What can a folate deficiency lead to?
Defects in protein synthesis
What is SAM?
(S-adenosylmethionine)
Precursor for methyl transfer reactions
Only transfers methyl groups
S-adenosylmethionine synthetase uses ATP to make S-adenosylmethionine. Methyltransferases will turn methyl acceptors into methylated products and make S-adenosylhomocysteine
What is required to convert norepinephrine to epinephrine?
SAM; S-adenosylmethionine
What is Biotin?
Water-soluble vitamin B7 cofactor
It helps to transfer one carbon group in the form of CO2
What are the One Carbon Pool Compounds?
- SAM - only transfers methyl groups
- THF - can carry many one carbon units
- Biotin - transfers carbon dioxide
How does Asparagine and Aspartate enter metabolism?
They enter as Oxaloacaetate
What is Asparginase?
It is an anti-cancer drug.
Normally, the body produces enough asparagine. Cancer cells are different in the way that they cannot produce enough asparagine, so the levels are already low in cancer patients. Asparaginase breaks down the what is left of the asparagine that is found in the blood, causing the cancer cells to die from asparagine deprivation.
Which amino acids enter metabolism as alpha-ketogluterate?
Glutamine, Proline, Arginine, Histidine
How is glutamate made?
The enzyme glutaminase converts glutamine to glutamate and NH3
How is glutamate made?
Proline is oxidized into glutamate
How is arginine degraded?
The enzyme arginase converts Arginine to Ornithine and then to Alpha-ketogluterate
How is Histidine degraded?
Histidine is oxidatively deaminated to Urocanic acid
Why is there a clincal test for folic acid deficiency?
A person without folic acid will excrete large amounts of FIGlu (N-Forminoglutamate) especially after ingesting Histidine. Without folic acid, the FIGlu cannot be converted into alpha-ketogluterate.
The test includes injecting the person with lots of Histidine and checking to see if they excrete N-formiminoglutamate. If so, there is a lack of folic acid.
Why is folic acid/ tetrahydrofolate important?
It converts Histidine to alpha-ketogluterate. Without it, there will be a build up in N-formiminoglutamate
What is Histidinemia?
Mutation in the enzyme Histidase, which normally would convert Histidine to Urocanic acid and eventually to alpha-ketogluterate. This causes a build up in Histidine in the blood and urine.
What is Alanine converted into?
Alanine aminotransferase converts alanine to pyruvate
What is Glycine converted to?
Serine hydroxymethyltransferase converts Glycine to Serine and then to Pyruvate
What is special about Cystine?
It is a dimeric amino acid formed by the oxidation of 2 Cysteine residues convalently bonded to make a disulphide bond
How does Cystine turn into Pyruvate?
Cystine is reduced using NADH+H into Cysteine and is converted to pyruvate with desulfuration
What amino acids form Fumarate?
Phenylalanine and Tyrosine
What is the fate of Phenylalanine?
The enzyme Phenylalanine hydroxylase converts Phynylalanine to Tyrosine which can be converted into either glucogenic Fumarate or ketogenic Acetoacetate
What amino acids form Succinyl CoA?
Methionine, Valine, Isoleucine, and Threonine
What are branched chain amino acids?
What is Maple syrup urine disease?
Which amino acids are able to pass the mitochondrial membrane?
Ornithine and Citrulline
Which amino acids are not used in proteins?
Ornithine and Citrulline
Which amino acid links the urea cycle with other metabolic pathways?
Fumarate
What medication can help with Hyperammonemia, and how?
Neomycin can kill bacteria that convert non-toxic intestinal urea into toxic ammonia that escapes into the bloodstream.
