Amino Acid III Flashcards
Synthesis of creatine requires?
glycine, arginine, and S-adenosylmethionine (SAM) (methyl group donor)
Use of Creatine
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
Creatine vs Creatinine
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)
Creatine Deficiencies
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
Products Derived from Tyrosine (5)
1) dopamine
2) norepinephrine
3) epinephrine
4) thyroid hormones
5) melanin
Synthesis of Dopamine, Norepinephrine and Epinephrine
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)
Aromatic Hydroxylase Enzymes
Phe, Tyr, and Trp; require THBtn
Parkinsonism
elderly, high frequency; degeneration of dopaminergic neurons; difficulty controlling voluntary muscle movements; no cure but patients administered DOPA
Thyroid Hormones Synthesis
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
Synthesis of Melanin
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
Albinism
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
Special Products of Tryptophan (3)
- Serotonin
- Melatonin
- Niacin
Synthesis of Serotonin
Trp —-(Trp Hydroxylase)—> 5-hydroxyTrp—-(decarboxylation)—> serotonin
Synthesis of Melatonin
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
Synthesis of Niacin
occurs in liver; Trp —(IDO)—>N-formylkynurenine
Indolamine-2,3-dioxygenase
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
Niacin Deficiency
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
Hartnup Disease and Trp
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
Special Products derived from Decarboxylation of AA’s
GABA and Histamine
Synthesis of GABA
gamma-aminobutyric acid; inhibitory neurotransmitter; decarboxylation of glutamate; Glu—(Pyridoxal Phosphate [B6])—> GABA
Synthesis of Histamine
decarboxylation of histidine; histamine = product of mast (immune) cells;
Glutathione and its purpose
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;
Glutathione and Drug Detoxification
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
