Biochem Quiz 9

Asparagine Synthesis

• Amidation of aspartate

• OAA → Aspartate via Transaminase

  • glutamate to a-kg

• Aspartate → Asparagine via Asparagine Synthetase

  • glutamine → glutamate

  • ATP → AMP + P

Asparaginase

• Can covert asparagine to aspartate by hydrolysis

• Deamidation

  • Removal of amino group from asparagine

Conditionally Essential Amino Acids

1. Arginine

2. Cysteine

3. Glutamine

4. Glycine

5. Proline

6. Tyrosine

Where is creatine synthesized?

• Muscles (mainly)

• Liver

• Kidneys

• Pancreas

Synthesis of Creatine

• Reactants: Arginine, Glycine, Methionine

• Enzyme: SAM (AdoMet) → AcoHcy

• Product: Creatine

Creatine is stored as _________ . This is created via the enzyme ________ .

phosphocreatine; creatine kinase

Creatinine

• waste product; indicator of renal function

• produced from breakdown of creatine

• occurs in muscle cells

Synthesis of Tyrosine

• Reactant: Phenylalanine

• Enzyme: Phenylalanine Hydroxylase

• Cofactor: BH4

• Product: Tyrosine

SAM/Ado-Met

• Methylating agent

• Most abundant methionine containing metabolite

• Formation of creatine and epinephrine

Methionine Cycle: SAM Synthesis

Methionine and ATP are converted into S-adenosylmethionine (SAM) by the enzyme methionine adenosyltransferase (MAT)

Methionine Cycle: Methylation

SAM donates methyl group to various substrates via methyl transferases, forming S-adenosylhomocysteine (SAH)

Methionine Cycle: SAH Hydrolysis

SAH is hydrolyzed by adenosylhomocysteinase (AHCY) to produce homocysteine and adenosine

Methionine Cycle: Remethylation

Homocysteine is recycled back into methionine via methionine synthase, utilizing vitamin B12 and 5-methyltetrahydrofolate (5-MTHF) as cofactors

Glutathione (GSH)

• Cellular reducing agent

• Derived from glutamate, cysteine, and glycine

Glutamate as a Neurotransmitter

• Main excitatory neurotransmitter

• Memory, cognition, mood regulation

Aspartate as a Neurotransmitter

Excitatory

Glycine as a Neurotransmitter

• Inhibitory

• Within spinal cord, brainstem, retina

Catecholamines

• Fight or flight response

• Require tyrosine for synthesis

• Dopamine, Norepinephrine, Epinephrine

GABA

• Need glutamate for synthesis

• Vitamin B6 dependent

• Inhibitory neurotransmitter

Serotonin

• Derived from tryptophan

• Mood regulation, sleep, digestion

Adenine

Adenine

• Purine

• Matches with thymine (DNA) or uracil (RNA)

Guanine

Guanine

• Purine

• Matches with cytosine

Cytosine

Cytosine

• Pyrimidine

Thymine

Thymine

• Pyrimidine

Uracil

Uracil

• Pyrimidine

• In RNA

De Novo Pathways: Nucleotide Biosynthesis

• Bases synthesized while attached to ribose

• Pyrimidine ring synthesized as orotate

• Glu provides most amino groups

______ is the precursor for purines

Gly

_____ is the precursor for pyrimidines

Asp

PRPP

Synthesis of PRPP

• Reactants: Ribose-5-phosphate and ATP

• Enzyme: PRPP synthetase

• Product: PRPP + AMP

CPS2

• cytosolic enzyme

• makes carbamoyl phosphate

• glutamine dependent

• transfer tunnel

Ammonia Transfer Tunnel of CPS2

• moves unprotonated ammonia from glutamine hydrolysis site

• prevents ammonia protonation

• allows for carbamate to be transferred to carbamoyl phosphate

Formation of Carbamoyl-Aspartate

Reactant: Aspartate, Carbamoyl Phosphate

Enzyme: ATCase

Product: N-Carbamoylaspartate

What is the CAD Complex?

CPS2, ATCase, DHD

Formation of Orotate (2) Steps

Step 1:

N-Carbamoylaspartate → L-Dihydroorotate via DHO (dehydration)

Step 2:

L-Dihydroorotate → Orotate via DHODH (oxidation)

• NAD+ reduced to NADH

orotate

OMP

Formation OMP

Reactants: Orotate and PRPP

Enzyme: OPT

Product: OMP

Formation of UMP

Reactant: OMP

Enzyme: OMP Decarboxylase

Product: UMP

UMP

Formation UTP

Reactant: UMP and 2 ATP

Enzyme: Kinase

Product: UTP

Formation of CTP

Reactants: UTP

• Gln → Glu

• ATP → ADP

Enzyme: CS

Product: CTP

CTP

Formation of TMP

• Thymidylate Synthase: dUMP → dTMP

• One carbon unit transferred from N5, N10 methylenetetrahydrofolate to dUMP

  • then reduced to a methyl group

• Dihydrofolate Reductase: reduces dihydrofolate to tetrahydrofolate

CPS2 inhibited by _______ and activated by _______

UTP; PRPP

ATCase Regulation

• Feedback Inhibition via CTP

• Accelerated by ATP

CTP Synthetase (CS 2 is form used in pyrimidine synthesis)

• Activated by GTP

  • Balances amounts of C and G