protein metabolism II Flashcards
- List the sulfer containing amino acids.
methionine (Met-essential) and cysteine (cys- unessential b/c it is synthesized from Met)
- Describe the biological utility of Cys in regard to its oxidative state (alone or within GSH).
The –SH can form disulfides with another Cys forming oxidized cystine, which is important for the structural integrity of many proteins (especially extracellular proteins). Also, cysteine is part of glutathione (GSH) which is a highly soluble tripeptide that controls redox potential via conversion to GSSG
functions of glutathione
- Thiol acts as redox buffer (SH buffer) to maintain proteins in reduced forms and regulate activity. 2. cofactor for glutathione transferase. 3. reduces H2O2 to water and protects against Reactive O2 species. 4. reduces heme to Fe2 to allow it to bind O2
Function of glutathione peroxidase
oxidizes GSH to GSSG- mutations lead to high breast cancer risk
function of glutathione reductase
reduces GSSG to GSG
function of glutathione- S- transferase
conjugation of GSH to agents- involved in detox, drug resistance,tumors
- Describe Met , its relation to SAM and the energy provided in SAM.
Met is used to produce S-adenosylmethionine which is an intermediate in cysteine production. SAM is converted to S-adenoyslhomocysteine (SAH) making SAM a major carbon/methyl donor and a high energy storage unit lik ATP
functions of SAM
Highly reactive- involved in methylation of proteins, nucleic acids, lipids, carbs. Plays role in epigenetics, cancer, maternal diet and depression
List rxn of Met to Cys
Met > SAM > SAH > homocysteine > cystathionine > cysteine
Describe Met recycling and cofactors needd
Met > SAM > SAH > homocysteine > Met. Homocysteine to Met requires Tetrahydrofolate and Vit B12
function of THF and B12 in Met recycling
A methyl group is transferred from THF to B12 to homocysteine to regenerate methionine
Hyperhomocysteinemia
elevated levels of homocysteine cause multiple problems that include cardiovascular disease. Results from low levels of folate, B6, & B12 (vascular disease). Cysteine is now essential and treat with folate, B6, & B12
Homocystinuria
Results from defect in cystathionine-b-synthase (CBS) and cannot convert homocysteine to cystathionine (and eventually cysteine). Leads to mental retardation, osteoporosis, & vascular disease. Cysteine is now essential. Can treat with Vit B6 to “force” CBS activity.
Cysteinuria
kidney stones (renal failure), due to defective in transporter of cysteine (& Ornithine, Lysine, Arginine) that leads to crystallization in urea, treat with acetazolamide that makes cysteine more soluble.
Effects of elevated homocysteine
vascular disease, impaired wound healing, cancer (cervical), cardiovascular mortality
products of tryptophan metabolism
pyruvate/acetyl coA or seretonin/melatonin/niacin
Co factor of tryptophan metabolism
Tetrahydrobiopterin cofactor (BH4)
products of phenylalanine metabolism
Phe > Tyr > DOPA > catecholamines or melanin
Phenylketonuria
defect in phenylalanine hydroxylase that leads to build-up of alternative byproducts (phenyllactate, phenylacetate, and phenylpyruvate).
List enzymes which BH4 is cofactor for
Phenylalanine hydroxylase, tyrosine hydroxylase and tryptophan hydroxylase
tyrosinemia
defect in any of the steps that convert tyrosine to fumarate and acetoacetyl CoA
parkinsons
Low dopamine due to destruction of neurons- treat with DOPA, MAOIs and catecholamine Mtase inhibitors
function of MAOs
breakdown DOPA, dopamine, NE and epi
