Amino Acid Catabolism - Urea Cycle

Front 1

Why is amino acid catabolism restricted to the liver?

Back 1

gluconeogenesis and urea cycle occur in the liver, (beta)-oxidation supplies the ATP needed for gluconeogenesis and urea cycle

Front 2

What must be done to an amino acid before it can be degraded?

Back 2

removal of the (alpha)-amino group

Front 3

What enzymes are responsible for the removal of the amino group from the amino acid?

Back 3

amino transferase funnels nitrogen into glutamate and generates an (alpha)-keto acid, glutamate dehydrogenase removes the amino group from the glutamate to form free ammonia

Front 4

What compound works along with aminotransferases to transfer the amino group from the amino acid to (alpha)-ketoglutarate (forming glutamate)?

Back 4

pyridoxal phosphate (PLP) vitamin B6, temporarily holds the amino group as it is transferred

Front 5

What is the "carbon skeleton" left after removing the amino froup from an amino acid

Back 5

(alpha) keto acid (e.g., oxaloacetate)

Front 6

What enzyme catalyzes the transfer of the amino group from alanine to (alpha) ketoglutarate?

Back 6

alanine aminotransferase (ALT), it is a reversible reaction

Front 7

What are the products of the alanine aminotransferase (ALT) catalyzed reaction?

Back 7

pyruvate from alanine and glutamate from (alpha)-ketoglutarate

Front 8

Which aminotransferase is considered an exception to the rule that most aminotransferases funnel amino groups into glutamate?

Back 8

aspartate aminotransferase (AST), used to form aspartate from glutamate (rather than the opposite)

Front 9

What liver enzyme is released to detect and monitor liver damage?

Back 9

serum aminotransferase, used in patients taking statin drugs, elevated levels do not necessarily indicate liver disease (muslce and kidney also release them)

Front 10

What mitochondrial enzyme catalyzes the reversible oxidative deamination of glutamate to form free ammonia, NADH, and (alpha)-ketoglutarate

Back 10

glutamate dehydrogenase

Front 11

What is the glutamate generated by amino acid catabolism used for?

Back 11

half is used to make free ammonia, the other half is used to make aspartate

Front 12

What are the sources of endogenous ammonia?

Back 12

primarily from amino acid catabolism using glutamate dehydrogenase, secondarily from degradation of purine and pyrimidine nucleotides, urea in the colon degrades to ammonia, intestine catabolizes glutamine to release ammonia, renal glutaminase degrades glutamine to ammonia

Front 13

What is ammonia used for?

Back 13

released in the urine as needed to balance pH

Front 14

How is ammonia disposed of?

Back 14

converted to urea or glutamine, each lower plasma ammonia (which is toxic)

Front 15

When is urea synthesized and where does it occur?

Back 15

urea cycle is always active (at varying rates), and it occurs in the liver

Front 16

What is the most abundant amino acid in plasma?

Back 16

glutamine

Front 17

What are the two sources of nitrogen in urea?

Back 17

one is from ammonia (from oxidative deamination via glutamate dehydrogenase), the other is from aspartate

Front 18

What is the rate limiting enzyme of the urea cycle and what reaction does it catalyze?

Back 18

carbamoyl phosphate synthetase I (CPSI), catalyzes the formation of carbamoyl phosphate from ammonia, ATP and CO2

Front 19

How much energy is required to detoxify ammonia (turn the urea cycle)?

Back 19

four ATP equivalents (ATP to AMP and two ATPs to ADPs)

Front 20

Which two compounds, within the urea cycle, cross the mitochondria?

Back 20

ornithine is transported in, citruline is transported out of the mitochondria

Front 21

The breakdown of which two amino acids results in acidic urine?

Back 21

sulfur containing amino acids, methionine and cysteine

Front 22

Is the Km of CPSI for ammonia high or low? What happens as ammonia levels increase?

Back 22

CPSI has a high Km for ammonia, as ammonia increases CPSI activity increases

Front 23

What are the allosteric effectors of CPSI and what are their effects?

Back 23

protons (acids)- negative effector
N-acetyleglutamate - positive effector

Front 24

How is N-acetylglutamate synthase regulated?

Back 24

substrate availability (glutamate + acetyl CoA), allosteric regulation by arginine (a positive effector)

Front 25

What factors decrease the activity of the urea cycle?

Back 25

low protein diet, high carbohydrate diet, fasting

Front 26

Besides urea, how is ammonia detoxified?

Back 26

conversion to glutamine via the "mop-up" reaction

Front 27

What is the "mop-up" reaction?

Back 27

in a cell separate from the urea cycle, the ammonia that escapes being converted to urea is converted to glutamine by glutamine synthetase (has a low Km for ammonia - CPSI has a high Km for amonia)

Front 28

What are the causes of hereditary hyperammonemia?

Back 28

any one of the five enzymes in the cycle may be missing

Front 29

What is the cause of hepatic cirrhosis?

Back 29

hepatocytes are replaced with fibroblasts (lack the urea cycle), results in higher ammonia levels

Front 30

What is the consequence of portal hypertension?

Back 30

blood is prevented from entering the liver, collateral circulation shunts blood away from liver (high ammonia blood)

Front 31

What does ammonia do at the blood brain barrier?

Back 31

it crosses the blood brain barrier → used to form glutamate → used to form glutamine (via glutamate dehydrogenase and glutamine synthetase, respectively)

Front 32

What do increased quantities of glutamate do in the brain?

Back 32

activation of N-methyl-D-aspartate (NMDA) receptors → ammonia toxicity

Front 33

What do increased levels of glutamine do in the brain?

Back 33

glutamine is osmotically active and cannot exit the brain → cerebral edema

Front 34

What is the therapy for acquired hyperammonemia?

Back 34

neomycin - reduces colonic bacteria that generate ammonia
lactulose - decreases absorption of ammonia in portal blood

Front 35

What is the therapy for hereditary hyperammonemia?

Back 35

low protein diet, phenylbutyrate, benzoate (conjugate with ammonia and are excreted in urine)