11/5 Nitrogen Metabolism Part Ii

Front 1

What does a high level of acetyl CoA indicate?

Back 1

energy rich environment. It's a product of fatty acids metabolism and metabolism of CHO

Front 2

Urea cycle will be driven in ______ _____ environment

Back 2

energy rich

Front 3

How do you make N-acetylglutamate?

What is it catalyzed by?

What is its purpose?

Back 3

acetate to alpha amino group of Glu

catalyzed by NAGS

enhance activity of CPS I

Front 4

What is a positive regulator of NAGS?

Back 4

Arg

Front 5

For the urea cycle there's a one-to-one need for what two molecules?

How do they stay in balance?

Back 5

Asp and NH4


Using Glu which can be catalyzed to either easily (AST^H) or glutamate dehydrogenase, such that NH4 <---> Asp

Front 6

What is the order of fuel preference for the body?

How do we sense a fasting state? How does this affect fuel usage?

Back 6

Glc (CHO), fats, amino acids

Urea cycle varies in fed/fasting states
Fed: ATP,GTP allosteric inhibitor of glutamate dehydrogenase (Glu rises, aa's don't feed into it)
Fasting: ADP,GDP allosteric activator of glutamate dehydrogenase (Glu falls, aa's converge to it)

Front 7

Errors of metabolism: it's usually a _____ gene and problems arise become of the _______ of the substrate behind the metabolic ______ or the ______ of the product in front of the metabolic _______

Back 7

single
accumulation block
deficiency block

Front 8

Describe clinical presentation of urea cycle disorders.

Back 8

See in full-term newborn after a day
Poor feeding, lethargy, emesis, hyperpnea, seizures (NH4)

Front 9

What points in urea cycle are vulnerable to leading to hyperammonemia?

Back 9

All enzymes (NAGS CPSI OTC ASS ASL) except arginase

Front 10

What makes OTC deficiency special?

Back 10

most common and only X-linked defect of urea cycle disorders. Only one that elevates orotic acid.

Front 11

NAGS and CPS I deficiencies have what type of outcome?

Back 11

Infant days in neonatal period. They're too important

Front 12

What makes arginase deficiency special?

Back 12

Doesn't really cause hyperammonemia. Low ornithine and high Arg. Arg exported to kidney where the renal isoform of Arginase is up-regulated 5x. Arg being high -> high NO

Neonatal course is uneventful until 2-4 yr progressive spastic diplegia (paralysis of both sides of body), quadriplegia, intellectual impairment, delayed growth, seizures

Front 13

What is the source of orotic acid in OTC deficiency?

Back 13

carbamoyl phosphate + Asp via CPSII makes orotate

Front 14

What other cause for hyperammonemia besides these urea cycle enzyme deficiencies?

Back 14

Lysinuric protein intolerance

Front 15

How do you treat hyperammonemia?

Back 15

Reduce nitrogen intake (protein)
replace missing nitrogen compounds (Orn if arginase)
remove excess ammonia (fructose --bacteria--> acidic by-products which + ammonia -> salts;
benzoate Gly scavenger, phenylacetate Gln scavenger, these are then excreted;
hemodialysis)

Front 16

How to make Asn?

Why is this important?

Where does this happen?

Back 16

Asp and NH4+ using asparaginase. Reversible.

Asn -> NH4+ + Asp (+ aKG) --AST-> oxaloacetate (put into citric acid cycle) + (Glu -> aKG + NH4+ + NADH (made into ATP using ox-phos)

Small intestine. NH4+ formed goes off to the liver.

Front 17

What five aa won't escape from small intestine?

Back 17

Asn Asp
Gln Glu
Arg

Front 18

Metabolic fate of Gln and Glu in enterocytes

Back 18

Gln --glutaminase--> Glu and NH4+
Glu ---glu dehydrogenase--> aKG (citric acid cycle) and NH4+
OR
glutaminolysis
Gln --->Glu + pyruvate -----alanine aminotransferase ALT-->Ala and aKG (Ala can go to liver to build glycogen/Glc)
pyruvate from aKG in CAC making malate ----malic enzyme---> pyruvate

Front 19

What's the third way to export nitrogen from enterocytes?

Back 19

convert Glu to have an aldehyde group (glu 5-semialdehyde dehydrogenase) and then ornithine aminotransferase (OAT) --> ornithine

which OTC is there to make ornithine into citrulline which it exports

Front 20

What is metabolic fate of Arg in enterocytes?

Back 20

NO is tightly regulated.

Arg --arginase--> ornithine ---OTC--> citrulline

Front 21

Which amino acids are metabolized because they could generate a NT?

Back 21

Asp Glu (these both just are) Arg (makes NO)

Front 22

So what all is metabolized in the small intestine?

Back 22

Asn and Asp --> ATP and NH4
Gln and Glu --> Ala ATP NH4+
Arg and Glu --> citrulline

Front 23

What kinds of consumption does small intestine do?

Back 23

Hyp for collagen
purine and pyrimidines for nuclei acids
small peptides (glutathione)
hormones enzymes other proteins