Protein Metabolism III: Sulfer and Aromatic Amino Acid Flashcards
sulful containing AA
cysteine (unessential)
methionine (essential
cysteine function
structural integrity of proteins (esp extracellular)
important role in redox potential
glutathione: tripeptide that controls redox potential via reversible reaction
Gsh–> Gssg
Methionine
produces intermediate in cysteine production: SAM
SAM
major carbon donor & high energy storage unit like ATP
Recycling MET rxn
MET>SAM>SAH>Homocysteine>Met
MET>SAM>SAH>Homocysteine>Crystathione>Cysteine
- Homocystein>Met requires THF and Vitamin B12 to transfer back CH3 group
- Homocysteine>Crystathione enzyme defective in homocystinuria, enzyme also requires B6
hyperhomocystemia
cause: low folate, B6, B12, vascular disease
Description: CV disease
AA: Cysteine becomes essential
Treat: Folate, B6, B12
homocystinuria
cause: defective CBS: can’t convert homocysteine>cysteine
description: mental retardation, osteoporosis, lens subluxation, tall with kyphosis, vascular disease, thrombosis, atherosclerosis (MI & Stroke)
AA: cysteine becomes essential
Treat: supplement B6 to force CBS activity
cysteinuria
cause: hereditary deficit of renal PCT and intestinal AA transporters for COLA (cysteine, ornithine, lysine, arginine)
Description: kidney stones/ failure
Diagnose: urinary cyanide nitroprusside test
Treat: Urinary alkinization (potassium citrate, acetazolamide); chelating agents
CBS enzyme
requires B6
reaction homocysteine> met
requires THF, vitamin B12
THF overview
¬ Synthesized in bacteria
¬ Precursor to folate
¬ One carbon group in any oxidative state is bonded to N-5 or N-10
THF Forms
Most reduced Form: methyl group
Oxidized Form: methylene group
Most Oxidized Form: methenyl, formyl, formin, or no group
Inter-convertable forms used to donate carbon in many reactions
GSH overview
¬ Redox Buffer
¬ Highly soluble tripeptide as opposed to Cys
¬ Milimolar in some tissues
GSH Functions
Thiol redox buffer = SH buffer; proteins in reduced form/ regulate activity
Enzyme cofactor for Gst (glutathione transferase)
Reduce Hydrogen peroxide to water; H202 H20; protects against ROS
Metabolism Products of tryptophan, phenylalanine, tyrosine
tryptophan: pyruvate or acetoacetate
Phenylalanine & tyrosine: fumerate or acetoacetate
Tryptophan Rxn
Tryptophan Hydroxylase: cofactor BH4
Trp»» serotonin (NT); melatonin (hormone); niacin (energy)
Phenylalanine Rxn
Phenylalanine hydroxylase: Cofactor BH4, deficient in PKU
Phe > Tyr
Tyrosine Rxn
Tyrosine hydroxylase: cofactor BH4
Tyr>Dopa»> Catecholamines (dopamine, NE, epinephrine)
PKU
Cause: deficient Phe hydroxylase or BH4 cofactor (malignant)
Description: excessive Phe leads to excess phenylketones in urine; Intellectual disability, growth retardation, fair skin, eczema, musty body odor
AA: tyrosine becomes essential
Screen: 2-3 days after birth/ after mom’s enzyme gone
Treat: decrease dietary Phe and increase tyrosine; avoid aspartame which contains Phe
maternal PKU
lack of proper therapy during pregnancy
Infant: microcephaly, intellectual disability, growth retardation, congenital heart defects
Akaptonuria
cause: deficient homogentisate oxidase in tyrosine degradation pathway to fumate
Description: dark connective tissue, brown pigmented scalar, urine black with exposure to air; debilitating arthralgia because homogentisic acid is toxic to cartilage
Treatment: low Phe diet with tyrosine
Albinism
cause: defect in Tyrosine metabolism and therefore deficiency in melanin production
Complete albinism: deficit tyrosinase
description: decreased pigmentation of eyes, hair, skin
Parkinson’s
dopamine is reduced in parkinson’s
one treatment is l-dopa which is dopamine precursor
MAOIs
MAO breaks down products of dopamine, NE, epinephrine, serotonin
hypertensive crisis with tyramine rich foods like cheese
