Amino Acid Metabolism + Urea Cycle

T/F: amino acids can be stored in the body

false

Glucose is stored in the body as

glycogen

Fats are stored in the body as

TAGs

Amino acids have to be obtained from what sources?

• diet

• synthesized de novo

• produced from protein degradation

The catabolism of amino acids involves the removal of what chemical? What does this release?

• nitrogen

• ammonia, urea, uric acid

Describe protein digestion in the stomach

• HCl denatures the protein

• HCl activates pepsinogen → pepsin

  • breaks complex proteins to polypeptides

Describe protein digestion in the pancreas

• protease enzymes break down polypeptides to oligopeptides

  • trypsin

  • chymotrypsin

  • elastase

  • carboxypeptidase

Describe protein digestion in the SI

• aminopeptidases cleave oligopeptides → small peptides and free AAs

Transamination is a reaction involving the removal of ___ from amino acids

• nitrogen

  • alpha-amino group

Transamination is a reaction that involves the transfer of the alpha-amino gorup to what intermediate? What does this produce?

• alpha ketoglutarate

• products: glutamate and alpha ketoacid

What enzymes catalyze transamination?

• aminotransferase

• prosthetic group: pyridoxal phosphate

What are the 2 aminotransferases?

• alanine aminotransferase (ALT)

• aspartate aminotransferase (AST)

Pyruvate, OAA, and alpha-KG are all ___ acids

alpha-keto

• C=O group on the C adjacent to the COOH group

What reactions does ALT catalyze?

• pyruvate → alanine

• glutamate → alpha-KG

What reactions does AST catalyze?

• glutamate → alpha KG

• OAA → aspartate

What is the reaction that results in the removal of the amino group as free ammonia?

oxidative deamination

Describe the process of oxidative deamination

• removes the amino group as free ammonia

• enzyme: glutamate dehydrogenase

• uses NAD+ or NADP+

• occurs in liver/kidney

• products: alpha ketoacids + ammonia

  • ammonia converted to urea (liver)

What is urea?

• disposal form of amino groups from AAs

  • derived from ammonia, aspartate, and CO2

• produced in the liver → transported in blood by kidneys → excreted in urine

Some urea is cleaved by ____ _____ in the intestine into ammonia, which is removed in the feces

bacterial urease

Describe the process of the urea cycle

1. CO2 provides the C atom in urea

2. free ammonia provides 1 N atom in urea

3. Carbamoyl phosphate synthetase I is required by N-acetyl-glutamate

   • acts as an allosteric activator

4. Citrulline is transported out of the mitochondrion → aspartate

5. amino group of aspartate provides another N atom in urea

6. aspartate → arginosuccinate

7. arginosuccinate → arginine

8. arginine → ornithine is regenerated + transported into the mitochondrion

9. fumarate is hydrated to malate

10. malate is oxidized to OAA

11. OAA is transaminated to aspartate

Describe the process of nitrogen elimination

• removal of alpha amino group of AA

  • transamination

  • oxidative deamination

• NH3 is toxic

• converted to urea in the liver → eliminated in urine

What are essential amino acids?

AAs we have to get from our diet

What are non-essential AAs?

• AAs we can synthesize

• has biosynthetic precursors in the carb and lipid pathways

Define glucogenic AAs

• catabolism yields pyruvate or TCA cycle intermediate

• substrates for gluconeogenesis

Define ketogenic AAs

• catabolism yields acetoacetate or acetyl CoA and/or acetoacetyl CoA

• substrates for ketogenesis

• they do not give rise to the net formation of glucose

What essential AAs are glucogenic?

• Histidine (His, H)

• Methionine (Met, M)

• Threonine (Thr, T)

• Valine (Val)

What are non-essential AAs are glucogenic?

• alanine (Ala, A)

• Arginine (Arg, R)

• aspartate (Asp, D)

• Cysteine (Cys, C)

• Glutamate (Glu, E)

• Glutamine (Gln, Q)

• glycine (Gly, G)

• Proline (Pro, P)

• Serine (Ser, S)

• asparagine (Asn, N)

What essential AAs are both glucogenic and ketogenic?

• Isoleucine (Ile, I)

• Phenylalanine (Phe, F)

• Tryptophan (Trp, W)

What non essential AA is both glucogenic and ketogenic?

• Tyrosine (Tyr, Y)

What essential AAs are ketogenic?

• Leucine (Leu, L)

• Lysine, (Lys, K)

What nonessential AAs are ketogenic?

none

What are the six families of AA biosynthesis?

1. glutamate family

2. aspartate family

3. serine family

4. alanine family

5. aromatic AA family

6. histidine

What is the source of the glutamate family?

alpha-KG (TCA)

What is the source of the aspartate family?

OAA (TCA)

What is the source of the serine family?

3-phosphoglycerate (gluconeogenesis/glycolysis)

What is the source of the alanine family?

pyruvate (glucogenic)

What is the source of the aromatic AA family?

• phopshoenolpyruvate

• erythrose 4-phosphate (pentose phosphate pathway/PPP)

What is the source of the histidine family?

ribose 5-phosphate (PPP)

What are the specialized products of AAs?

• porphyrins (Hb)

• creatine (muscle mass)

• NTs (5-HT, catecholamines)

• purines + pyrimidines (nucleic acids)

• other N containing compounds (melanin)

Alanine and pyruvate are interconverted by which enzyme?

alanine aminotransferase

In the urea cycle, ornithine transcarbamoylase catalyzes:

formation of citrulline from ornithine and another reactant

What enzyme converts arginine into urea and ornithine?

arginase

Which reaction associated w/ the urea cycle occurs in the cytosol?

synthesis of arginosuccinate

In which pair of compounds is the second molecule produced by the deamination of the first molecule?

• glutamine and glutamate

• aspartate and OAA

• alanine and pyruvate

Deamination of MOST AAs in the liver is accompanied by the conversion of:

alpha-KG to glutamate

Which statement is true regarding the conversion of arginine to ornithine in the urea cycle?

The enzyme catalyzing this reaction is a hydrolase.

• arginase

Urea synthesis in mammals takes place primarily in tissues of the:

liver

Glutamate is metabolically converted to α-ketoglutarate and NH₄⁺ by a process described as:

oxidative deamination

Which cofactor is typically required in transamination rxns?

pyridoxal phosphate

Which amino acid can be considered to be both glucogenic and ketogenic?

tyrosine

Which statement is false regarding ketogenic and glucogenic amino acids?

a) Glucogenic amino acids cannot be used to make ketone bodies.

b) Ketogenic amino acids can be used to synthesize fatty acids.

c) Leucine and isoleucine are both exclusively ketogenic amino acids.

d) Both valine and threonine catabolism produce succinyl-CoA.

Leucine and isoleucine are both exclusively ketogenic amino acids.

Which amino acids are both ketogenic and glucogenic?

1. isoleucine

2. valine

3. histidine

4. arginine

5. tyrosine

1 and 5

Which two amino acids are exclusively ketogenic?

leucine and lysine

Amino acids are divided into biosynthetic families according to the fact that there are:

six types of important metabolic precursors.

Select all that apply. Essential amino acids are:

• leucine

• glycine

• alanine

• histidine

• tryptophan

leucine, histidine, tryptophan

Which compound can be described as glucogenic and ketogenic?

phenylalanine

In amino acid catabolism, the first reaction for many amino acids is a(n):

transamination requiring pyridoxal phosphate (PLP).