Amino Acid III

Question 1

Synthesis of creatine requires?

Answer 1

glycine, arginine, and S-adenosylmethionine (SAM) (methyl group donor)

Question 2

Use of Creatine

Answer 2

when ATP conc. is high in muscle, creatine is -P’ed by creatine kinase (acts as energy reserve); is a phosphate donor for ADP when rapid use of ATP is occurring in muscles

Question 3

Creatine vs Creatinine

Answer 3

Creatine (2%) cyclizes to form creatinine (metabolic end product); released from muscle cells and into urine; amount of creatinine excreted is proportional to muscle mass; monitor creatinine levels over time they shouldnt change but if they do then there might be kidney impairment (increase creatinine = decreased kidney function)

Question 4

Creatine Deficiencies

Answer 4

hypotonia in children but display very little skeletal or cardiac muscle pathology; do have lots of neurological symptoms (seizures and epilepsy); treatment = supplementation w/ creatine in diet

Question 5

Products Derived from Tyrosine (5)

Answer 5

1) dopamine
2) norepinephrine
3) epinephrine
4) thyroid hormones
5) melanin

Question 6

Synthesis of Dopamine, Norepinephrine and Epinephrine

Answer 6

sequential modification in catecholeamine producing cells (level of modification depends on what cell needs); Tyr—(Tyr Hydroxylase)—> DOPA—-(DOPA decarboxylase)—>Dopamine—(dopamine beta-hydroxylase)—> Norepinephrine—-(Norep. N-methyltransferase)–> Epinephrine (SAM is methyl donor)

Question 7

Aromatic Hydroxylase Enzymes

Answer 7

Phe, Tyr, and Trp; require THBtn

Question 8

Parkinsonism

Answer 8

elderly, high frequency; degeneration of dopaminergic neurons; difficulty controlling voluntary muscle movements; no cure but patients administered DOPA

Question 9

Thyroid Hormones Synthesis

Answer 9

20-30% of Tyr residues on thyroglobulin are iodinated by thyroid peroxidase; some iodinated Tyr’s are coupled together; once Thyroglobulin degraded by lysosomes, T3 and T4 are released

Question 10

Synthesis of Melanin

Answer 10

from Tyr in golgi of melanocyte cells; Tyr—(tyrosinase)–> DOPA—-> dopaquinone, which is metabolized to give different melanin colors; melanin passed to keratinocytes; melanin provides protection against UV radiation

Question 11

Albinism

Answer 11

range of defects in pigmentation; most common = oculocutaneous albinism type 1 (OCA1) = loss of tyrosinase function = complete inablility to synthesize melanin; white hair, white skin, irides look pink; complications = vision impairment and skin tumors early on

Question 12

Special Products of Tryptophan (3)

Answer 12

1. Serotonin
2. Melatonin
3. Niacin

Question 13

Synthesis of Serotonin

Answer 13

Trp —-(Trp Hydroxylase)—> 5-hydroxyTrp—-(decarboxylation)—> serotonin

Question 14

Synthesis of Melatonin

Answer 14

pineal gland produces serotonin; serotonin used in production of melatonin; Serotonin—(N-acetyltransferase)—> N-acetylserotonin—(hydroxyindole O-methyltransferase [+SAM])—>melatonin; pineal gland has light/dark cycles and it releases melatonin in dark cycle to induce sleepiness

Question 15

Synthesis of Niacin

Answer 15

occurs in liver; Trp —(IDO)—>N-formylkynurenine

Question 16

Indolamine-2,3-dioxygenase

Answer 16

converts Trp to N-formylkynurenine; possible anti-cancer drug target; tumors escape immune detection by activating IDO to deplete Trp and create lots of Trp metabolites that interfere w/ proliferation of T-cells that would be involved in tumor destruction

Question 17

Niacin Deficiency

Answer 17

from lack of niacin itself OR from lack of Trp in diet; pellagra can result from lack of micronutrients required for conversion of Trp to niacin even if there is enough Trp; pellagra = dermatitis, diarrhea, dementia, death

Question 18

Hartnup Disease and Trp

Answer 18

Hartnup affects ability of intestine to uptake Trp and ability of kidney to resorb it; if Hartnup left untreated then pellagra-like symptoms can develop from not enough Trp uptake; Treatment w/ high protein diet and administration of niacin

Question 19

Special Products derived from Decarboxylation of AA’s

Answer 19

GABA and Histamine

Question 20

Synthesis of GABA

Answer 20

gamma-aminobutyric acid; inhibitory neurotransmitter; decarboxylation of glutamate; Glu—(Pyridoxal Phosphate [B6])—> GABA

Question 21

Synthesis of Histamine

Answer 21

decarboxylation of histidine; histamine = product of mast (immune) cells;

Question 22

Glutathione and its purpose

Answer 22

tripeptide Glu-Cys-Gly w/ gamma-glutamyl linkage (C=O of R-group bonded to alpha-amino group on next AA); very resistant to protease cleavage; intracellular reducing agent, scavenges free radicals, destroys peroxides and conjugates toxic molecules for excretion; GSSG dimer forms when oxidized;

Question 23

Glutathione and Drug Detoxification

Answer 23

Glutathione S-transferase catalyze transfer of glutathione to molecules that contain reactive -O, -S, and -N groups (prevents them from interacting w/ proteins and protects cell environment from damage; thioether linkage between glutathione and the toxic compound