22 - Sulfur Amino Acid Synthesis Flashcards
How is inorganic sulfur fixed (ie reduced to become available for biosynthesis)?
- Sulfate is activated by addition of ATP to form phosphoadenosine 5’-phosphosulfate (PAPS) in two ATP-dependent steps
- PAPS is then reduced (2 electron acquisition) to sulfite and then to sulfide with NADPH as cofactor (consumes lots of this = expensive)
- Sulfite reductase also requires FAD, FMN and a cofactor with an Fe-S centre
PAPS is also utilized in the biosynthesis of sulfated proteoglycans
How are cysteine and methionine synthesized in plants and bacteria vs. mammals?
PLANTS AND BACTERIA
- Aspartate from oxaloacetate in TCA is converted to homoserine. Homoserine is converted to cystathionine, which is converted to homocysteine, which is converted to methionine.
OR
- 3-PG is converted to serine. Serine is converted to cysteine (FIRST STEP always). Cysteine is then converted to cystathionine, which is converted to homocysteine and then to methionine.
Cysteine: synthesized from methionine and serine IN MAMMALS
Give steps for the synthesis of cysteine in plants and bacteria
The reaction is to exchange O to S, not easy. Therefore there is a need to activate by substitution of acetate using high energy of CoA ester (acetate is a better leaving group than hydroxyl, can be displaced by sulfide)
- Activation of serine with acetate via acetyl-CoA.
- Acetone can then be displaced by the sulfur ion from H2S
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Give steps for the synthesis of cysteine and then methionine in plants and bacteria
The reaction is to exchange O to S, not easy. Therefore there is a need to activate by substitution of acetate using high energy of CoA ester (acetate is a better leaving group than hydroxyl, can be displaced by sulfide)
- Activation of serine with acetate via acetyl-CoA.
- Acetone can then be displaced by the sulfur ion from H2S to form cysteine
- Uses vitamin B12 (cobalamin) or tetrahydrofolate (THF) as methyl donor. Methionine synthase catalyzes addition of methyl group to form methionine
In mammals, the carbon skeleton for cysteine is derived from ___
serine
In mammals, cysteine sulfur is supplied by ___
methionine
In mammals, to donate the sulfur atom, methionine is first activated to ___?
S-adenosylmethionine (Ado-Met or SAM), an important methyl group donor.
In mammals, the reverse of methionine biosynthesis resembles?
Biosynthesis of cysteine!
Which cofactor is required for teh deamination and splitting of cystathione to cysteine?
Pyridoxal phosphate
It’s used in the condensation and dehydration steps
Net reaction is to replace the hydroxyl of serine with thiol from methionine and the loss of the methyl group on methionine.
Many foods are supplemented with folic acid. What is its purpose in the biosynthesis and catabolism of amino acids?
Converted to THF, which is involved in the transfer of groups containing one carbon atom (common in both processes)
- Reactions usually involve participation of biotin, tetrahydrofolate or S-adenosylmethionine (SAM) as cofactor
What transfers carbon in its most highly oxidized state (ie CO2)?
What transfers carbon in its most reduced form (CH3)?
What transfers carbon in states intermediate of these two?
CO2: biotin
CH3: S-adenosylmethionine (SAM)
Intermediate redox states: tetrahydrofolate (THF) from folic acid
What is folic acid?
A vitamin produced by bacteria.
- Converted to tetrahydrofolate by the enzyme dihydrofolate reductase
- One carbon group undergoing transfer is covalently linked to the pteridine moiety at N5, N10 or both.
- Various forms are interconvertible through oxidation or reduction (explains versatility of THF)
What is a major source of one carbon units?
Carbon removed during the conversion of serine to glycine, with production of N5,N10-methylenetetrahydrofolate
However, the transfer potential of the tetrahydrofolate methyl group is usually not sufficient for many biosynthetic reactions.
SAM is a more potent methyl group donor than THF, as it is 1000 times more reactive than methyl-THF
How is SAM produced?
SAM is produced by metabolic activation of methionine by the enzyme methionine adenosyl transferase
ATP is used, but rather than releasing pyrophosphate, it releases triphosphate. Sulfur able to replace alpha phosphate.
SAM can methylate purines to convert them to histidine
Many methyltransferase enzymes use SAM as methyl donor (eg. phosphatidylethanolamine methyltransferase).
What is an exception to this and why?
SAM does not participate in the methylation required to produce methionine itself. The methionine synthase reaction uses methylcobalamin as methyl group donor.
This is to prevent futile cycling
