Amino acid metabolism

Question 1

Body needs aa for..

Answer 1

Protein synthesis
Energy sources- gluconeogenesis
Neurotransmitters- eg serotonin, dopamine
Nucleotide synthesis

Question 2

Source of aa in body

Answer 2

Proteins in diet (exogenous)
Breakdown of body’s own proteins (endogenous)
Biosynthesis

Question 3

Amino acid deamination (how ammonia is lost/transferred to another acceptor in exchange rxn)

Answer 3

1. Transamination

2. Oxidative deamination

Question 4

Importance of transamination

Answer 4

• Funnelling of alpha-amino grps of amino acids into glutamate for conversion into NH3
• Synthesis of nonessential aa

Question 5

Transamination steps

Answer 5

Stage 1. Conversion of aa to keto acid
-formation of amino acid-PLP (Pyridoxal 5’-P) Schiff base
-Formation of alpha-keto acid and (pyridoxamine-5’-P) PMP
Stage 2. Conversion of alpha-keto acid to an aa
-PMP reacts with alpha-keto acid to form Schiff base
-alpha keto acid-PMP Schiff base tautomerizes to form amino acid-PLP Schiff base
-Regeneration of Enzyme-PLP complex

Question 6

Oxidative deamination (enzyme)

Answer 6

Glutamate dehydrogenase (GDH)

Question 7

What do glucogenic and ketogenic aa breakdown into?

Answer 7

Gluogenic aa: degraded to glucose precursors

Ketogenic aa: broken down to acetyl-CoA or acetoacetate and can thus be converted to fatty acids or ketone bodies

Question 8

What is a critical cofactor for transaminases (Aminotransferase)

Answer 8

PLP Pyridoxal-5’-phosphate

Question 9

Glutamine Synthetase regulation by…(2enzymes)

Answer 9

Adenylyltransferase and uridilyltransferase

• Glutamine is amino grp donor for many biosynthetic products
• Primary storage form of ammonia

Question 10

Glutamine transamination from…

Answer 10

alpha-ketoglutarate

Question 11

Glutamine synthesized from..

Answer 11

Glutamate catalyst- Glutamine synthetase

Question 12

Allosteric feedback inhibitors of Gln Synthetase

Answer 12

His, Trp, carbamoyl phosphate, glucosamine-6-phosphate, AMP and CTP-end products starting with Glutamine
-Ala, Ser, Gly- reflect cell’s Nitrogen lvl

Question 13

Glutamine synthetase: Differences btw bacterial and mammalian forms

Answer 13

Mammalian enzyme activated by alpha-ketoglutarate, which is an end-pdt of oxidative deamination of glutamate
This activation prevents accumulation of ammonia produced by deamination rxn

Bac Gln synthetase

• Allosteric feedback inhibitors: 9, indpt binding sites and cumulative effectors
• Covalent modification

Question 14

Regulation of bac Gln synthetase

Answer 14

-Regulatory adenylyltransferase composed of enzyme component-AT and regulatory component PII
-the same enzyme catalyzes adenylation and deadenylation.
Unmodified PII- makes AT catalyze adenylation,
uridylylated PII- makes AT catalyze deadenylation

Uridylylation/deuridylylation activity catalyzed by another Uridyltransferase (UT) which adds/removes UMP to regulatory component PII
Only uridylylation is regulated, deuridylalation is not regulated
-when [Glutamine] high, Uridylylation of PII is inhibited (leads to decreased deadenylylation of Gln synthetase
-When [alpha-ketoglutarate] high, Uridylyltransferase to PII is activated (leads to increased deadenylylation of Gln synthetase)