Biochem Of Met, Block 2, # 8: Nitrogen Met, Urea Cycle

Front 1

When do you want to oxidize amino acids, and what's the general overivew of the process?

Back 1

When diet is rich in amino acids, when have more than are needed for synthesis, during starvation/uncontrolled diabetes.

3 step process: amino acids loose amino group and become a ketone skeleton. The ketone skeleton is oxidized or converted to gluconeogenic compounds.

ammonia is converted to urea.

Front 2

what major intermediate is the amonia transfered to before becoming urea?

Back 2

Carbomyl Phososphate.

Front 3

Digestion of proteins - where does it happen and what major enzymes are used?

Back 3

Stomach: pepsin and gastrin

Pancreas: trypsin and secretin

Small intestines: absorb proteins

Most oxidation of AA's happens in the liver.

Front 4

If happening in the liver, what's the first big step of protein oxidation?

What about outside the liver?

Back 4

Start with an amino acid and an ALPHA KETO GLUTERATE. The nitrogen is going to get put on to the alpha keto gluterate to form GLUTAMATE.

The remaining ketone body is an ALpha Keto Acid.

catalyzed by AMINO TRANFERASE and requires PLP cofactor.

Outside the liver, amino group is transferred to an ALANINE or GLUTAMINE.

Front 5

What carriers exist to bring in nitrogen from other cells, and where are they coming from?

Also, what do these carriers break down into?

Back 5

Alanine and Glutamine:

Alanine comes ONLY FROM MUSCLES:

glutamine can come from muscles or other tissues (e.g., brain).

Alanine looses amino and becomes pyruvate (pyruvate is its alpha keto acid).

Glutamine has 2 amino groups - loose one and become glutamate, loose 2 and become alpha keto gluterate.

Front 6

Glucose and Alanine in muscles - what happens during strenous exercise in relation to amino acid breakdown?

Back 6

oxygen eventually runs out, yielding an excess of pyruvate. if don't want to run through anerobic respiration, can shuttle pyruvates away.

pyruvate reacts with glutamine to form alanine (pyrutave + amino group = alanine) and alpha ketogluterate (glutamine minus its nitrogen).

Catalyzed by ALT (alanine transaminase).

Alanine goes to liver, un-done back to pyruvate and do gluconeogenesis, which puts glucose back into the blood.

Front 7

If alanine brings in from muscles, what's going on with glutamine? How is it made, and when it's in the liver, what happens to it?

Back 7

In tissues: glutamine synthetase adds nitrogen to glutamate to make glutamine (costs ATP). Glutamine transferred to liver.

Liver uses Glutaminase to break off nitrogen and make glutamate.

Front 8

Once you've made glutamate in the liver, how do you get the nitrogen off to turn it into urea? What happens to the glutamate?

Back 8

Need Glutamate Dehydrogenase! Turns your glutamate back into alpha keto gluterate.

Front 9

Once you have free nitrogen off glutamate, what's the overall picture of what's accomplished?

Back 9

NH3 plus Hco3- and arpartate are converted to urea (2 nitrogens on it) and fumarate (CAC intermediate), at the cost of 3 ATP.

Front 10

Okay: 4 steps after freeing of nitrogen. What's the first? Where does it happen?

Back 10

Amonia and carbonic acid to make CARBAOMOYL PHOSPHATE, via carbamoyl-p-synthetase 1, requiring 2 ATP.

Happens in mitochondria

Front 11

What's the next step?

Back 11

Carbomyl reacts with ornathine to make CIRTRULLINE using ORNATHINE TRANSCARBOMYLASE.

Citrulline can leave the mito and enter the cytosol.

Front 12

3rd reaction?

Back 12

Citrulline + Asparate go to arigininosuccinate, via ariginosuccinate synthase.

NOTE: costs 1 ATP.

Front 13

Where does aspartate come from?

Back 13

Comes from oxaloacetate: it gets a nitrogen from glutamate via AST (aspartate transaminase), a liver function test enzyme.

Front 14

4th reaction?

Back 14

Auriginosuccinate to Fumarate and Arginine, via aurriginosuccinitase.

Front 15

5th reaction?

Back 15

arginine to ornithine and urea, via arginase = END OF CYCLE.

Front 16

what's a treatment for trying to deal with high urea? What's the problem having lots of extra amonia around?

Back 16

lactulose.

Amonia toxcisity can come from using up all your CAC intermediates in the flushing of urea.

Also, benzoate and glycene can be used as treatment options.

Front 17

How is amonia generally moved around the blood?

Back 17

as alanine or argenine.

Front 18

How is the urea cycle regulated?

Back 18

Long term depends on the synthesis of all the enzymes involved.

Short term can be turned on indirectly by Argnine, acting on CPS-1

Glutemate and acetyl CoA can make N-Acetyl Gluteate via N-Acetyl Glutemate Synthase.

N-Acetyl Glutemate turns on CPS-1.

Arginine turns on N-Acetyl Glutemate Synthase, making more, turning on CPS-1, driving the urea cycle.