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Flashcards in Protein Biochemistry 3 Deck (19)
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Sulfur-containing amino acids (2) and their importance

  • Methionine
  • Cysteine
  • Important because sulfur plays critical roles in protein formation through disulfide bonds
  • Disulfide bonds exist primarily in extracellular environment (membrane receptors)
  • Can control catalysis by changing enzymes from active to inactive forms


Biological utility of Cys in regard to oxidative state

  • Oxidized form makes disulfide bonds for structural integrity of proteins
  • Reduced form occurs when these bonds are broken
    • Integral part of tertiary protein structure and fxn


Role of glutathione (GSH) as reducing agent and "SH buffer"

  • GSH = product of HMS shunt off of glycolysis (along with ribose)
  • As a reducing agent: allows formation, breakage, and reformation of correct disulfide bonds --> allows for proper protein folding
  • Has a key sulfur branch (off its cysteine group) to make this possible
  • GSH much more soluble than Cys alone


4 functions of GSH

  1. Acts as redox buffer ("SH buffer") to maintain proteins in their reduced forms --> important for intracellular functions + regulates enzyme activity
  2. Cofactor for several enzymes (glutathione transferase, GST)
  3. Reduce hydrogen peroxide to water, provides general protection against reactive oxygen species
  4. Keeps heme reduced for functional hemoglobin --> heme iron must be ferrous (Fe2+) to bind O2


Met's relationship to SAM & energy provided in SAM

  • Met + ATP (SAM synthase) --> SAM
  • Sulfur group on SAM is very high energy, unstable, reactive --> allows attached methyl to be easily transferred
  • SAM = energy storage unit similar to ATP
    • Less stable
    • Stores energy as methyl group, not as phosphate group


Main functions of SAM & targets of this process

  • SAM utilized to transiently store high energy from ATP in form of methyl group on SAM molecule
  • Serves many biological roles
    • Charged sulfur involved in methylation, epigenetics, host defenses, cancer, maternal diet, depression
  • Homocysteine = product of Met/SAM pathway
  • SAM as methyl group donor:
    • Norepinephrine --> epinephrine
    • Cysteine residues --> DNA 


Tetrahydrofolate: source & uniqueness compared to SAM

  • THF created during regeneration of methionine from homocysteine
  • Comes from vitamin B9 (folic acid) - which comes from leafy greens & enriched cereals
  • Key for synthesis of AAs and nucleic acids
  • Unique compared to SAM - 
    • In addition to donating CH3 it also donates CH2, formimino (CH=NH), and formyl (CH=O)


Key steps in conversion of methionine --> homocysteine --> methionine & key co-factors

  • 2 key cofactors:
    • B12 + N5-methyl THF
    • Methyl group transferred from THF to B12 to homocysteine


Diseases related to Cys, Met metabolism (3)

  1. Hyperhomocysteinemia
  2. Homocystinuria
  3. Cysteinuria



  • Elevated levels of homocysteine --> cause multiple problems including CV disease
  • Caused by low levels of B9 (folate), B6 (PLP), B12 --> vascular disease
  • Cysteine becomes an essential amino acid (can't be made by body & must be supplemented)
  • Treat with folate, B6, B12



  • Defect in cystathionine-ß-synthase (CBS)
  • Leads to mental retardation, osteoporosis, dislocation of lens, & vascular disease
  • Cysteine now essential (cannot be made by body & must be supplemented)
  • Treat with vit B6 to "force" CBS activity



  • Defective transporter of cysteine across membrane
  • Prevents reabsorption
  • Leads to crystillization in urea
  • Treat with acetazolamide --> makes cysteine more soluble
  • Also drink a lot of water
  • Causes kidney stones + renal failure


Use of vitamins (folate, B6, B12) in Cys, Met metabolism

  • B12 & THF: involved in conversion of homocysteine --> methionine (transfer of methyl group)
    • Methyl group transferred from THF --> B12 --> homocysteine --> methionine
  • B6/PLP: involved in conversion of homocysteine --> serine --> cystathionine --> cysteine
    • B6 converted into PLP 


Biologically important molecules derived from Trp metabolism (3)

  • Trp is glucogenic and ketogenic
  • Yields:
    • Serotonin (NT)
    • Melatonin (hormone)
    • Niacin (vitamin)


Diseases related to Phe, Tyr metabolism (2)

  1. Phenylketonuria (PKU)
  2. Tyrosinemia I/II/III


Diseases related to MAO inhibitors (2)

  1. Parkinsons Disease
  2. Depression



  • Defect in phenyalanine hydroxylase
  • Now need a new pathway to get to needed intermediates
  • Common inherited disorder, infants have musty odor
  • Phenylalanine (phenylalanine hydroxylase) --> tyrosine



  • Hydroxylation of tyrosine --> catecholamines is preserved
  • However, second step of aromatic amine decarboxylases (3 types) is defective
    • Fumacylacetoacetase
    • Tyr aminotransferase
    • Hydroxyphenylpyruvate dioxygenase


Parkinsons Disease

  • Loss of dopamine-producing neurons in basal ganglia
  • Leads to loss of dopamine and movement disorders
  • Treat with DOPA, MAOIs, catecholamine methyltransferase inhibitors