Mstn Ii - Lecture 28

Front 1

Urea takes place in:

Back 1

both the mitochondria and the cytosol

first 2 steps: mito
last 3: cytosol

Front 2

Urea cycle step 1:

key regulatory point

Back 2

- Carbamoyl Phosphate Synthetase I (CPS I)
- carbamoyl phosphate from bicarbonate and ammonia
- concomitant hydrolysis of 2 ATP molecules
- in mito

- attachment of 1st urea nitrogen
- donated from ammonia

Front 3

2nd step in urea cycle:

Back 3

- ornithine transcarbamoylase transfers the carbamoyl group from the carbamoyl phosphate onto ornithine in the synthesis of citrulline
- citrulline is transported from mito into the cytosol

Front 4

step 3 of urea cycle:

Back 4

arigininosuccinate synthetase catalyzes the acquisition of the 2nd nitrogen atom from aspartate.
- citrulline ureido group is condensed with the aspartate amino group to yield argininosuccinate.

- attachment of the 2nd nitrogen group
- ATP is hydrolized into AMP + PPi
- expend 2 high energy bonds

Front 5

step 4 of urea cycle

Back 5

argininosuccinase
- cleaves the aspartate carbon skeleton off of the argininosuccinate in the form of fumarate (a CAC intermediate).

- fumarase can convert the fumarate into malate.
- malate dehydrogenase can convert malate into OAA

- now left with arginine

Front 6

step 5 of urea cycle

Back 6

arginase

catalyzes the hydrolysis of arginine to yield urea and regenerate ornithine, which is transported back into the mito

Front 7

Assimilation of 2 N into urea requires:

Back 7

4 high-energy bonds from ATP.

Front 8

Ornithine

1 out of 2 ways of regulation of urea cycle

Back 8

- key factor in the synthesis of urea
- can be made from arginine as seen in Step 4, but is also derived from the amino acid, glutamate. If glutamate is limited, then the ornithine is also limited, slowing down urea cycle.

Front 9

CPS 1 reaction

2/2 ways of regulating urea cycle

Back 9

- allosterically activated by metabolite N-acetylgluamate synthase
- metabolite is synthesized from glutamate and acetyl-CoA by the enzyme N-acetylglutamate synthesis.
- which in turn is activated by arginine.

- N-acetylglutamate is degraded by a specfic hydrolase.

Front 10

the more acetyl CoA and glutamate present:

Back 10

the more the body needs to eliminate excess nitrogen, the more the urea cycle is driven forward.

Front 11

hydrolysis of high energy bonds in the urea cycle:

Back 11

2 ATP in step 1

1 ATP in step 3

PPi in step 5

Front 12

conversion of fumarate into malate produces:

(step 4)

Back 12

1NADH

Front 13

NADHs are produced when:

Back 13

- step 4: conversion of Fumarate into Malate

- glutamate dehydrogenase converst glutamate into ammonium ions and alpha-ketoglutarate

Front 14

link between urea cycle and citric acid cycle:

Back 14

- aspartate
- urea cycle in step 3

- via the formation and breakdown of argininosuccinate

Front 15

linkage between the urea cycle and the CAC helps:

Back 15

maintain blood glucose levels by maintaining gluconeogenesis

Front 16

all the starting materials for gluconeogenesis are located in the:

Back 16

cytosol