Protein Metabolism II: Nitrogen

Question 1

control point of urea cycle

Answer 1

carbomoyl phosphate synthase I: mitochondria
uses 2/3 ATPs used in cycle
allosteric activation via n-acetyltransglutamate (synthesis dependent on Argenine)

Question 2

allosteric activator of control enzyme in urea cycle

Answer 2

n-acetyltransglutamate

n-acetylglutamate synthase activated by arginine

Question 3

Glutamine

Answer 3

Glu Dehydrogenase= control point
controls the direction of nitrogen removal/ incorporation of AA

Glu Synthase: Glutamate–> Glutamine for transport in liver to urea cycle

Question 4

Alanine

Answer 4

transport in muscle; alanine/glucose cycle

pyruvate –> alanine: transport to liver
alanine –> pyruvate: gluconeogenesis back to muscle

Question 5

Arginine

Answer 5

crosstalk and alternative reactions to urea cycle

NO synthase: Arginine –> citrulline + NO

Arginase: Arginine –> ornithine: produces creatine phosphate for muscle energy

Question 6

Ketogenic

Answer 6

no net production of glucose

lysine & leucine are only ketogenic because their breakdown gives Acetyl CoA (2 carbons)

Question 7

glucogenic

Answer 7

produces pyruvate or kreb cycle intermediates

oxaloacetate in kreb cycle from aspartate transamination

Question 8

MSUD

Answer 8

deficient a-keto dehydrogenase
blocked oxidative carboxylation of branched AA (isoleucine, leucine, valine)

CNS deficits, Intelectual Disability, Death
buildup a-ketoacids in urine: sweet smelling
increased a-ketoacids in blood: especially leucine

Question 9

MSUD Tx

Answer 9

restrict dietary leucine, isoleucine, valine

thiamine supplementation

Question 10

hyperammonemia

Answer 10

acquired or hereditary from urea cycle enzyme deficiencies

excess NH4 depletes a-ketoglutarate –> Inhibition of TCA cycle

Question 11

Ammonia Intoxication symptoms

Answer 11

tremor (asterixis)
slurred speech
somnolence
vomiting
cerebral edema
blurred vision

Question 12

hyper ammonemia treatment

Answer 12

limit dietary protein

Benzoate/ phenylbutarate: bind to AA and lead to excretion

Lactulose: acidify GI tract to trap NH4 for excretion

Question 13

how to differentiate N-acetylglutamate deficiency from carbamoyl phosphate synthetase I deficiency?

Answer 13

Increased ornithine with normal urea cycle suggest n-acetylglutamate deficiency

Question 14

ornithine transcarbamylase deficiency

Answer 14

most common urea cycle disorder (x-linked recessive)

usually presents first few days of life
increased orotic acid in blood/urine
decreased BUN
hyperammonemia symptoms

NO megaloblastic anemia bc different from orotic acuduria

Question 15

Neomycin (oral)

Answer 15

can be used to treat hyper ammonia by reducing number of urease producing bacteria in the gut

Question 16

Phenylbutyrate (prodrug)

Answer 16

phenylacetate (active drug)

combines with glutamine to form phenylacetylglutamine to be excreted in urine

assists in nitrogen clearance from blood

Question 17

Tyrosine products

Answer 17

prohormone T4 and active hormone T3

Question 18

TSH

Answer 18

stimulated iodide (I-) uptake and release of T3, T4
TBG (thyroxin binding globulin): transports T3, T4

Question 19

rate limiting step in porphyrin production

Answer 19

aminolevulinate synthase: gly + sucinyl CoA –> Ala

mitochondria
decreased by Heme & glucose
increased by p450 inducers

Question 20

enzymes effected in lead poisoning

Answer 20

aminolevulinate dehydrase (cytosol)
2ALA --> Porphobilinogen

ferrochelatase (mitochondria)
Protoporphyrin IV –> heme

Question 21

Bilirubin in blood

Answer 21

via albumin

Question 22

bilirubin in Liver

Answer 22

bilirubin –> bilirubin diglucuronide (conjugated bilirubin)

Question 23

Bilirubin in intestine

Answer 23

bilirubin diglucuronide –> sterobilin

Question 24

Relationship between Heme and aminotransferases

Answer 24

decreased heme = increased ALA synthase
Increased heme = decreased ALA synthase

*??Negative feedback

Question 25

Lead poisoning substrates & symptoms

Answer 25

substrates in blood: protoporphyrin, ALA

microcytic anemia, GI/Kidney disease
Children: mental deterioration
Adults: headache, memory loss, demyelination

Question 26

Acute Intermittent Porphyria

Answer 26

enzyme: porphobininogen deaminase
substrate: porphobilinogen, als, coporphobilinogen (urine)

Symptoms: 5Ps
Painful Abdomen
Port wine colored urine
Polyneuropathy
Psychological disturbances
Precipitated by drugs, ETOH, Starvation

hepatic

Question 27

treatment for Acute Intermittent Porphyria

Answer 27

glucose and Heme to inhibit ALA synthetase

Question 28

drug relationship to porphyrias

Answer 28

Cytochrome P-450 inducers precipitate attacks because P-450 reduces Heme, which increases ALA synthase synthesis

results in increase of heme precursors

*relates to hepatic porphyrias

Question 29

Prophyria Cutanea Tarda

Answer 29

most common prophyria
Enzyme: uroporphyrinogen decarboxylase

Substrate: uroporphyrin (red-brown urine)

Blistering cutaneous photosensitivity

mixed hepatic/ erythropoietic