Nitrogen Metabolism

Question 1

AA production from the following enzyme activations:

1. peptidase
2. trypsin
3. chymotrypsin
4. elastase

Answer 1

1. peptidase - Phe, Tyr, Glu, and Asp
2. trypsin - Arg and Lys
3. chymotrypsin - Phe, Tyr, Trp, and Leu
4. elastase - Ala, Gly, and Ser

Question 2

Hartnup Disease

Answer 2

Genetic metabolic disorder that affects the absorption of neutral amino acids (GAVLIMPFW)
Most of the symptoms are caused by lack of essential amino acids
No tryptophan to synthesize niacin (B3)

Question 3

Cystinuria

Answer 3

Genetic metabolic disorder that affects the absorption of cysteine and basic amino acids (His, Lys, and Arg)
Only one essential amino acid-lysine (hard to see signs of deficiency)
High levels of cysteine in kidneys and bladder led to formation of kidney stones

Question 4

Steps of Ubiquitin

Answer 4

1. Protein is conjugated via a thioester bound to ubiquitin-activating enzyme (E1)
2. Ubiquitin is transferred to a Cys sulfhydryl group on the ubiquitin-conjugating enzyme (E2)
3. Ubiquitin-protein ligase (E3) transfers the activated ubiquitin to a Lys group on the target protein
4. Ubiquitinylated proteins are degraded in the proteasomes
   * Must get rid of damaged proteins before they harm your body!

Question 5

Marasmus

Answer 5

Child suffers from slowed growth and loss of muscle
Serum albumin levels are normal
Extremities are emaciated

Question 6

Kwashiorkor

Answer 6

Protein intake is low, but total calorie intake is near normal 
Hypoalbuminemia
Causes edema
Areas of hyperpigmentation 
Fatty liver

Question 7

Cystic Fibrosis

Answer 7

can cause a blocked pancreatic duct resulting in decreased secretion of digestive enzymes
Treated with pancreatic enzymes
Concentrations of the enzymes need to be increased as the patient ages

Question 8

Defected CPS1

Answer 8

low urine orotate, low blood citrulline and arginine, and high blood NH3

Question 9

Defected OCT

Answer 9

high urine orotate (due to build up of carbamoyl phosphate), low blood citrulline and arginine, and high blood NH3

Question 10

Defected Argininosuccinate Synthetase

Answer 10

extremely high citrulline (>1000 uM), low blood arginine and high blood NH3

Question 11

Defected Argininosuccinate Lyase

Answer 11

moderately high citrulline (200uM), low blood arginine, and high blood NH3

Question 12

Defected Arginase

Answer 12

high blood arginine and moderately high blood NH3

Question 13

Essential Amino Acids

Answer 13

Arg, His Ile, Leu, Lys, Met, Phe, Thr, Trp, Val

Question 14

Nonessential Amino Acids

Answer 14

Ala, Asn, Asp, Cys, Glu, Gln, Gly, Pro, Ser, Tyr

Question 15

Pseudo- Essential

Answer 15

Cys and Tyr; considered non essential, but they are synthesized from an essential AA (Cys from Met and Tyr from Phe)

Question 16

Pathways of AA Synthesis

1. Pyruvate
2. Oxaloacetate
3. alpha-ketoglutarate
4. 3PG/Glu
5. Phe

Answer 16

1. pyruvate makes Ala via PLP/B6
2. oxaloacetate makes Asp via PLP/B6 which makes Asn
3. alpha-ketoglutarate makes Glu via PLP/B6 which makes Pro, Asn, Asp, and Gln
4. 3PG/Glu makes Ser which makes Gly and Cys via PLP/B6
5. Phe makes Tyr via BH4

Question 17

Tetrahydrofolate

Answer 17

is a CH3 donor for several AA reactions and nucleotide metabolism; consumed via vitamin folate

Question 18

Ketogenic

Answer 18

Lys and Leu

Question 19

Both Ketogenic and Glucogenic

Answer 19

Ile, Phe, Thr, Tyr, Trp

Question 20

Glucogenic

Answer 20

Gly, Ala, Val, Met, Pro, Arg, His, Glu, Gln, Ser, Asn, Asp, and Cys

Question 21

Maple Syrup Urine Disease

Answer 21

Caused by a defect in enzymes that degrade branch chain amino acids (BCAA)
Branch chain amino acid build up in the blood and urine: Valine, Isoleucine, & Leucine
Makes urine smell like maple syrup (sweet smelling)
Several different classifications
Treated with a special diet low in BCAAs
BCAAs make up 25% of typical protein

Question 22

Phenylketonuria (PKU)

Answer 22

Caused by mutations to the gene that encodes for phenylalanine hydroxylase (PAH)
PAH catalyzes the reaction of phenylalanine to tyrosine
Mutation in PAH causes phenylalanine concentrations to be elevated- causing brain/mental defects
PKU can also be caused by defects in tetrahydrobiopterin (cofactor for PAH)
Treated with a diet low in phenyalanine

Question 23

Tyrosinemia I

Answer 23

Caused by defects in enzymes that break down tyrosine
Type 1- Fumarylacetoacetate hydrolase
Most severe form of the disease
Often presents as failure to thrive in infants
Leads to liver and kidney failure and problems with the nervous system
Diet must be controlled

Question 24

Tyrosinemia II

Answer 24

Caused by defects in enzymes that break down tyrosine
Type 2- Tyrosine aminotransferase
Affects eyes, skin and mental development
Diet must be controlled

Question 25

Alcaptonuria

Answer 25

Caused by a accumulation of homogentisic acid due to a defect in the enzyme homogentisate oxidase Accumulation of homogentisic acid leads to cartilage damage in the spine and lower back pain Arthritis May also cause heart disease

Question 26

Purine Synthesis

Answer 26

R-5-P converted to IMP via 11 enzymes using 6 ATP IMP makes AMP and GMP (reversible/salvaged) IMP to AMP uses 2 enzymes and 1 GTP where Asp acts as N donor IMP to GMP uses 2 enzymes and 1 ATP where Gln acts as N donor build the base on top of PRPP

Question 27

Control of Purine Biosynthesis 1. GMP to GTP (3 inhibitions) 2. AMP to GTP (3 inhibitions) 3. GTP and ATP (1 stimulation)

Answer 27

increased GTP (from GMP) stimulates AMP production increased ATP (from AMP) stimulates GMP production AMP to ATP and GMP to GTP inhibits PRPP synthase and GPA enzymes, which synthesize IMP GMP inhibits its own side's enzyme IMP dehydrogenase AMP inhibits its own side's enzyme adenylsuccinate synthetase

Question 28

Pyrimidine Synthesis

Answer 28

Gln to UMP using 6 enzymes and 2 ATP UMP is converted to CTP and UTP base formed first then add PRPP dTTP isn't converted to the ribonucleotide

Question 29

What makes up the Purine Rings? (C, N, and both)

Answer 29

C = HCO3-. Formate (2), and Glycine (2) N = Aspartate amine, glutamate amide (2), glycine Both: glycine

Question 30

Formation of dNTPs

Answer 30

not synthesized de novo reaction catalyzed by ribonucleotide reductase proper ratio is essential because otherwise can cause mutations (if too much or little of a dNTP)

Question 31

What makes up the Pyrimidine Rings? (C, N, and both)

Answer 31

``` C = HCO3- N = Aspartate and Glutamine ```

Question 32

Purine Degradation

Answer 32

Does not get back cost of energy, so more likely to be salvaged If broken down = uric acid in urine excess uric acid = gout Pyrimidine degradation does not cause any problems 90% of cases = lack of excretion Tx: allopurinol to inhibit xanthine oxidase

Question 33

Adenosine Deaminase Deficiency

Answer 33

enzyme for purine salvage Causes severe problems in the immune system The body isn’t able to produce T cells or B cells Child must be placed in a sterile environment to survive If HGPRT deficient = self mutilation/ mental defects