Lecture 16-20

Question 1

Ammonotelic

Answer 1

NH3 excreting (ex: fish)

Question 2

Uricotelic

Answer 2

Uric acid excreting (ex: birds)

Question 3

Ureotelic

Answer 3

Urea excreting (ex: mammals)

Question 4

Ornithine transcarbamoylase

Answer 4

Mitochondrial enzyme. Carbamoyl-P comes from mitochondrial CPS-I rxn
Ornithine + carbamoyl-P <> Citrulline + Pi

Question 5

Argininosuccinate synthase

Answer 5

Cytosolic enzyme. Isomerizes citrulline to form imide and OH, then it adenylates the OH to prime Asp addition
Citrulline + Asp + ATP <> Argininosuccinate + AMP + PPi

Question 6

Arininosuccinate lyase

Answer 6

Cytosolic enzyme

Argininosuccinate <> Arg + Fumarate

Question 7

Arginase

Answer 7

Cytosolic enzyme

Arg + H2O <> Ornithine + Urea

Question 8

N-acetyl-glutamate synthase (NAGS)

Answer 8

Glu + Arg indicators of high amino acid content. Glu is substrate and Arg allosterically activates NAGS. NAGS deficiency results in hyperammonemia (requires NAG analogue - carbamoylglutamate)
Glu + acetyl-CoA <> N-acetyl-Glu + CoA

Question 9

N-acetyl-Glu (NAG)

Answer 9

Allosteric activator of CPS-I and needed to start urea cycle.

Question 10

Ornithine transcarbamoylase disorder

Answer 10

Most common inherited urea cycle disorder. Found in males and heterozygous females. Phenotype ranges from neonatal hyperammonemic coma to asymptomatic adult. Ammonia concentrations can increase rapidly causing ataxia, lethargy, and death.

Question 11

Arginase disoder

Answer 11

Untreated individuals have episodic hyperammonemia of varying degree (usually not life-threatening). Usually normal at birth and childhood (because Arg required for growth)

Question 12

Liver acinus

Answer 12

Biological ammonia trap. Endothelial lining is fenestrated (full of openings to expose hepatocytes to blood –> direct contact b/n hepatocytes and blood components). Allows rapid metabolite exchanges b/n liver and blood. Periportal hepatocytes rely on glutaminase and urea cycle. Perivenous scavenger cells use Gln synthetase.

Question 13

Arginine

Answer 13

Urea cycle intermediate. Synthesis from diet, cell protein turnover. Broken down into nitric oxide and citrulline.

Question 14

Creatinine and creatine-P

Answer 14

Uncatalyzed breakdown of creatine-P to creatinine. Yield depends on muscle mass and clearance rate indicates kidney function. Creatine is phosphorylated by ATP to create ATP-buffer in muscles

Question 15

Glutamate

Answer 15

Synthesized by transamination of aKG (transaminase), reductive deamination (GDH), or hydrolysis (glutaminase)

Question 16

Glutamine

Answer 16

Synthesized by glutamine synthetase

Question 17

Aspartate

Answer 17

Synthesized by transamination of OAA(transaminase) and hydrolysis (asparaginase)

Question 18

Asparagine

Answer 18

Synthesized by asparagine synthetase (CPS2-like enzyme)

Question 19

Alanine

Answer 19

Synthesized by transamination of pyruvate

Question 20

Alanine shuttle

Answer 20

Inter-organ transfer of ammonia nitrogen as alanine to prevent ammonia toxicity

Question 21

Proline

Answer 21

Reduction of glutamate into glutamate semi-aldehyde (transaminated into ornithine). Then cyclyzed and reduced by NADH into proline

Question 22

Hydroxyproline

Answer 22

Use of prolyl hydroxylase and O2 to make hydroxyproline. Enzyme relies on iron which must be reduced by vitamin C (absence of vitamin C destabilizes collagen –> scurvy)

Question 23

Serine

Answer 23

Synthesized in two pathways from 3-phosphoglycerate

Question 24

Tyrosine

Answer 24

Synthesized from phenylalanine by phenylalanine hydroxylase. Enzyme deficiency leads to PKU

Question 25

Cystenine

Answer 25

Synthesized from methionine. Met adenylated into SAM. SAM transfers methyl group in other rxns and becomes SAH which is hydrolyzed into homocysteine. Addition of serine and cleavage forms cysteine

Question 26

Thyroxin

Answer 26

T3 is active form. T4 converted into T3 by peripheral deiodinase. T3 targets all cells and binds to mobile receptors/TFs. Affects gene expression and increases basal metabolic rate. Not necessary for life, helps growth, development, and metabloism

Question 27

Amino acid neurotransmitters

Answer 27

Glutamate, aspartate, D-serine, glycine. Some AAs are converted into other neurotransmitters (E, F, W)

Question 28

Amino acid-derived neurotransmitters

Answer 28

Gamma-aminobutyric acid derived from glutamate decarboxylation (enzyme requires vitamin B6). Racemization of L-serine forms D-serine (enzyme requires vitamin B6)

Question 29

Heme biosyntesis

Answer 29

Complex series of enzymatic steps in both mitochondria and cytosol (first step in mitochondria = condensation of succinyl CoA and Gly into ALA)

Question 30

Anemia

Answer 30

With iron deficiency, Sn replaces Fe and impairs heme synthesis. Pb can inhibit heme synthesis.

Question 31

PRPP

Answer 31

Ribose-5-phosphate + ATP <> PRPP + AMP

PRPP + base <> nucleoside-5-P + PPi
PPi + H2O > 2 Pi (pulls first rxn in forward direction)

Question 32

CTP synthetase

Answer 32

Formed from UTP and uses CPS2-like mechanism. CS-1 essential for CDP-diacylglycerol formation. CS-2 is rate limiting enzyme in biosynthesis of RNA/DNA pyrimidines. CS-2 is activated by GTP (maintains purine/pyrimidine balance)