- Intermediate created: Carbamoyl phosphate
- Enzyme: Carbamoyl Phosphate Synthetase
> Requires ATP

> Major point of regulation

> 1. Activation of bicarbonate with ATP, to form carboxyphosphate

> 2. Addition of ammonium

> 3. Activation of carbamic acid with ATP to form carbamoyl phosphate

> Anhydride bond, higher transfer potential

- Carbamoyl Phosphate Synthetase is responsible for substrate channeling - prevents loss of intermediates


Carbamoyl Phosphate Synthesis

- Ornithine + Carbamoyl Phosphate -> Citrulline
- Enzyme: Ornithine transcarbamylase
- Citrulline is transported to the cytosol


Formation of Citrulline (in mitochondrial matrix)

- Reaction requires ATP and is driven forward by PPi cleavage
- Citrulline + Aspartate -> Argininosuccinate
- Enzyme: Argininosuccinate synthetase


Formation of Argininosuccinate (cytoplasm)

- Argininosuccinate -> Arginine + Fumarate
- Enzyme: Argininosuccinase
- Carbon Skeleton Link to TCA cycle

Formation of Fumarate

- Arginine -> Ornithine + Urea
- Enzyme: Arginase
- Ornithine transported from cytosol to MT (mitochondrial matrix) to join the urea cycle
- Urea given off in urine


Cleavage

1. Transamination to make aspartate
2. Condensation with acetyl CoA to make citrate -> energy
3. Gluconeogenesis -> energy export
4. Conversion to pyruvate then to Acetyl CoA for fatty acid synthesis

Four fates of OAA (Oxaloacetate)

- 1st amino group from ammonium, second amino group from aspartate, carbon comes from bicarbonate
- ** Fumarate is formed from the breakdown of argininosuccinate in the urea cycle, and links the urea cycle with the TCA cycle
- First reactions occur in the mitochondrial matrix

OVERVIEW
- Carbamoyl Phosphate synthesis
- Formation of Citrulline (in mitochondrial matrix)
- Formation of Argininosuccinate (cytoplasm)
- Formation of Fumarate
- Cleavage

- Eventually converted to OAA, cycle can start again


Michigan State University

Amino acids make up every protein. There are 20 total amino acids each with a unique side-chain group. Some additional amino acids are listed, but only 20 are coded from DNA directly. These side-chains allow for chemical interactions like sulfide bonds, hydrogen bonds, and ionic bonds. Amino acids are further divided by being non-polar, polar, and charged. They link together with a peptide bond making a string of amino acids a polypeptide. Finally, each amino acids is assigned a name, a three-letter symbol and a one-letter symbol. 


Amino Acids are involved in many systems and issues with its breakdown can cause diseases: 
- In the liver: major site of urea production in the urea cycle
- Alpha-keto acids can deliver amino groups to the liver 
- Ammonium is toxic: lethargy, headache, vomiting, seizures, death
- Seen in compromised liver


Amino Acids

- Enzyme: Glutamate dehydrogenase
- 1. Oxidation (NAD+ or NADP+) of glutamate to yield Schiff-base intermediate
- 2. Hydrolysis deamination of intermediate to make alpha-ketoglutarate
- Glutamate -> alpha-ketoglutarate and ammonium
- Mitochondrial enzyme: NH4+ is toxic
> Reactions close to equilibrium

> Usually pulled forward by loss of NH4+


Oxidative deamination of amino acids to yield glutamate in liver

Urea Cycle

- Phenylketonuria (PKU)
- Alkaptonuria
- Maple-Syrup urine disease

Inborn Errors of Amino Acid Catabolism

Protein structure is the 3-dimensional assembly caused by the string of amino acids translated from RNA . Protein structures varies immensely due to the assembly of the amino acids.
There are four subdivisions of proteins structures:
- Primary structure
- Secondary structure
- Tertiary structure 
- Quaternary structure 

Learn Before

Related

Learn After