Part 5 Flashcards
Theory on why essential AAs and inessential AAs are consumed vs. synthesized in humans
Estimated 59 enzymes required to make all essential AA
- expensive to synthesize
- survival advantage to consume from diet - maybe they are less important?
17 enzymes required to make non-essential AA
- easier to synthesize, less expensive
- survival advantage to maintain capacity to synthesize
trace production of special products
To measure rate of synthesis and track involvement of AA in other products being synthesized
AA involved in glutathione synthesis
Glu, Cys, Gly
These AA are involved in many other synthetic pathways for special products including:
ATP production
Nucleic acid production
Mucins
Creatine
Taurine
Neurotransmitters
Rate of synthesis and source of dispensible AA
High flux rates and glucose as ultimate precursor (de novo synthesis mostly)
- synthesis of AA accounts for 8% if total BMR
Exceptions to glucose as precursor for dispensible AA:
1) Tyr from Phe (essential)
2) Cysteine sulfur from methionine (essential), skeleton is derived from glucose/serine
Synthesis of cysteine from methionine pathway (and taurine)
1) Methionine is demethylated –> homocysteine
2) Homocysteine + serine –> cystathionine
3) Methionine portion (a-ketobutyrate + NH4+) is removed –> cysteine
4) Cysteine by multiple steps –> taurine
Methionine demethylation-remethylation cycle
Methionine from: diet, and proteolysis
1) Methionine + ATP –> S-adenosyl-methionine (SAM)
2) SAM –> S-adenoysl-homocysteine (SAH) + R-CH3
- demethylation step
3) SAH –> Homocysteine + adenosine
4) Homocysteine + methyl-cobalamin (B12) + N5-methyl-THF (folate) –> methionine + folate (THF)
5) Homocysteine + PLP (pyroxyl phosphate, B6) –> cystathionine
6) Cystathionine + PLP –> Cysteine + a-ketobutyrate +NH4+
Folate cycle
1) Homocysteine + N5-methyl-tetrahydro folic acid (+methyl cobalamin/B12) –> THF + Methionine
2) THF + PLP (B6) –> 5,10N-methyl-THF + glycine
3) NADPH (B3) + FAD (B2) + 5,10N-methyl-THF –> N5-methyl-THF + NADP+
- produces folate available for homocysteine conversion
Cysteine requirement in infants
Taurine is an essential AA for
Infants can have a bottle neck at Homocysteine –> Cystathionine and may require increased cysteine (significant because cysteine is not stable in solution so must be given intravenously)
Babies cannot produce enough taurine
Vitamin deficiency that can lead to cysteine deficiency
Vitamin B6 deficiency can lead to cysteine deficiency
Required for:
Homocysteine –> cystathionine
Cystathionine –> cysteine
Double methylation of THF (folate) to recycle active form (N5-methyl-THF) for homocysteine –> Met conversion
Issues related to sulfur AA
Methylation reactions - folate cycling requires B6 (PLP), B2 (FAD) and B3 (NADPH)
Vitamin deficiencies - ex. B6 deficiency no PLP for transamination reactions in cysteine production
Homocysteine - ex. folate or B12 deficiency leads to build up of homocysteine
Liver function - Met/homoCys cycle occurs in liver and requires good liver function
Premature infants cannot make enough cysteine or taurine
Glutathione synthesis requires cysteine
Glutathione structure and role
Necessary for
Cysteine as a precursor
Structure: y-glutamyl-cysteinyl-glycine
Role: intracellular protection against oxidative stress
- conjugation with electrophiles
- removal of ROS
- glutathionylation of proteins
Needed for:
Protection of proteins, lipid membranes and DNA
Immune system function
Erythrocyte function
Cysteine required for synthesis - autooxidized cystine transported into cells and then broken up (expensive process)
Glutathione depletion based on nutritional status
Highly regulated synthesis
Glutathione depletion during:
short term fasting and protein deficiency (↓ synthesis)
burns and AIDS (↑ oxidants)
- additional protein does not increase glutathione synthesis
Why are glutathione supplements useless?
Would just be hydrolyzed in the gut and taken up as amino acids (expensive amino acid supplement)
