Transcript Sulphur Containing Amino Acids

A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
Sulphur Containing
Amino Acids
• They are methionine,cyseine,cystine.
• Methioinine is essential.
• It serves as precursors for the
synthesis of cysteine and cystine.
• Both are non essential.
• Cysteine and cystine are
interconvertable.
• The sulphur-containing AA are an
exclusive dietary source of sulphur in
the body
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
Sulphur containing Amino Acids
Cystine
Cysteine
CH3
Methionine
S
(CH2)3
CHNH2
COOH
Methionine
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
Methionine is essential ,it serves as precursor
for the synthesis of cysteine and cystine.
Methionine and cysteine present in proteins.
The sulfur containing amino acids are almost
an exclusive dietary source of sulfur to the
body.
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
Methionine
(Amino Acid that form Succinyl CoA)
.
It is one of four amino acids that form succinyl CoA.
It is converted to s-adenosylmethionine(SAM),the
major methyl- group donor in one carbon
metabolism.
It is also a source of homocysteine – a metabolite
associated with atherosclerosis and vascular
disease.
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
Metabolism of
Methionine
3 parts
•
• Utilization of methionine for
transmethylation reactions.
• Conversion of methionine to
cysteine and cystine.
• Degradation of cysteine and its
conversion to specialized products
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
Metabolism of Sulphur containing Amino
Acids(Cystein, cystine Methionine:
Cysteine Biosynthesis
Cysteine is synthesized from essential
A.A.
methionine
Ist Step:
ATP+Methionine
Methionine
adenosyl
transferease
S-Adenosyl methionine
SAM serve as precursor for methyl group
ex. Nor epinephrine
Epinephrine
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
• S-Adenosylmethionine is highly reactive
due to the presence of a positive charge.
The enzyme involved in the transfer of
methyl group are called
methyltransferase.
• S-AM transfer the methyl group to an
acceptor and gets itself converted to Sadenosylhomocysteine.
• The loss of free energy in this reaction
makes the methyl transfer irreversable.
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
2nd step:
S-Adenosylmethionine
S-Adenosyl homocysteine
SAM release its methyl group to a methyl acceptor forming SAdenosyl homocysteine
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
3rd Step:
S-Adenosyl homocystinase
S-Adenosyl homocysteine
Homocysteine+ Adenosine
S-Adenosyl homocysteine is cleaved by the homocysteinase enzyme
to give homocysteine and adenosine need H2O and doesn't need any
catalytic action.
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
• S-Adenosylhomocysteine is
hydrolysed to homocysteine and
adenosin
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
4th Step:
Cystathionine synthetase
Homocysteine + Serine
Cystathionine
This step is a condensation of homocystine with AA serine
to form cystathionine need catalytic enzyme synthetase
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
Cystasthionine lyase
5th step:
Cystathionine
Cysteine+ α ketobutyrate
Lyses of cysthionine to form cysteine
and αketobutyrate by the enzyme
cystathionine lyase.
Fate: Cysteine is needed for protein
synthesis and other body need.
αketobutyrate is decarboxylated to
propionyl CoA.
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
Degradation
&resynthesis of
methionine
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
After donation of the methyl group ,SAdenososylhomocysteine is hydrolysed to
homocystein and Adenosine.
Homocysteine has 2 fate:
Fate of homocysteine
If there is a deficiency of methionine
,homocysteine may be remethylated to
methionine.
Or if there is adequate amount of
methionine ie stores are adequate
homocysteine may enter the
transsulfuration pathway ,where it is
converted to cysteine
16
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
Fate1: if inadequate stores of
methionine
Homocysteine accept a methyl
group from N –methyl THF in a
reaction requiring
methylcobolamine (co B12) .
The methyl group is transferred from B12
derivative to homocysteine
17
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
Degradation
&resynthesis of
methionine
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
19
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
Metabolic Diseases Related to
Sulphur Amino Acids
Homocysteinuria:
# It is related to methionine metabolism.
# It is autosomal recessive disease.
#It is inborn error of metabolism due to
deficiency of Cystathionine synthetase.
.(step 4).
#Accumulation of homocystine and Its
appearance in the urine.
# Cataract, Mental retardation, Taller than
other group.
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
#Harmful treatable disease if
diagnosed early.
#Diagnosis by amino acids analysis
in the urine.
#Increase homocystine in the urine.
#Treatment is supply of milk with no
methionine and added cystein.
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
Relationship of homocysteine to vascular disease
Elevation of homocysteine accelerate oxidative
damage inflammation and endothelial dysfunction ,and
independent risk factor for occulsive vascular disease.
Epidemiological studies have shown that that plasma
homocysteine is inversly related to the plasma levels
of folate, B12 and B6 ,the three vitamine that involved
in the conversion of homocysteine to methionine and
cysteine
Supplementation of these vitamines has been
shown to reduce circulating levels of
homocysteine .
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
Relationship of homocysteine to vascular disease
In addition large elevation of homocysteine in
blood as a result of rare deficiency in
cystathionine synthetase are seen in patients with
classic homocysteinuria .
These individuals experience premature vascular
disease with about 25% dying from thrombotic
complications before 30 years of age.
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
Cystinuria
#Autosomal recessive inherited
abnormality of tubular reabsorption.
#Excessive excretion of dibasic amino
acids cystine, ornithine,arginine &lysine
(25-40)times normal.
#The defect is in the renal reabsorption
mechanism
24
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
Cystinuria
#Cystine is relatively insoluble and become
of a high concentration in the urine.
#precipitate to form renal calculi. (cystine
calculi).
#Diagnosis by demonstrating excessive
excretion of cystine in the urine.
#Management is to prevent calculi formation
by reducing urine concentration. High fluid
intake, urinary alkalinizer , penicillamine.
25
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
Cystinosis
#Rare but serious disorders of cystine
metabolism.
#Excessive deposition of cystine in different
organ, kidney, bone marrow, cornea,
conjunctiva.
#Generalized aminoaciduria with glucosuria.
#Harmful untreatable disease end with early
death.
#Defect is unknown, may be due to impaired
in the transport of cystine from the affected
cells.
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
Creatinine
# It is one of the final product of Arginine,
Glycine & Methionine.
#Creatine present in muscles, brain& blood.
#Creatinine is the anhydride of creatine
formed by irreversible non enzymatic
dehydration of muscle creatine.
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
Schematic presentation of creatinine
biosynthesis
NH2
NH4
C
Arginine-glycine transamidination
Arginine
Kidney
5-Adenosylmethionine
5-Adenosylhomocystine
Glycocyamine
ATP
ADP
Muscle- non enzymatic dehaydration Creatine
Creatinine
phosphate
H2O+pi
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
Creatinine is normally released from
skeletal muscles to the circulation in a
constant manner and excreted through
complete filtration without reabsorption.
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
Interpretation of serum creatinine should
consider certain factors:
1. Lower in children than adult, lower in female than
male & lower during pregnancy .
2.Certain drugs(salicylate&cimitidine) increase
creatinine by inhibiting tubular secretion of
creatinine.
3.Some endogenous substances (acetoacetate) may
affect the analytical method of measurement of
creatinine
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
Serum Creatinine is indirect measurement
of Glomerular Filtration Rate (GFR)
Increase in serum creatinine is likely due to
a fall in GFR.
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
Increase serum Creatinine( Decrease
GFR) could be due to:
1.Any diseases lead to impairment of renal
perfusion.
2.Diseases lead to loss of the functioning
nephrons (Acute&chronic
glomerulonephritis).
3.Diseases whose pressure is increased on
tubular side of the nephrons.
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
Serum Creatinine is indirect measurement
of Glomerular Filtration Rate (GFR)
Increase in serum creatinine is likely due to
a fall in GFR.
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
Creatinine can be used for in the
measurement of creatinine clearance
(index of GFR)
UV
---------------PX1440
U: Urine Creatinine.
V: 24 hours urine volume.
P: Plasma creatinine.
I440: 24X60
A
m
I
n
o
A
c
I
d
S
M
E
T
A
B
O
L
I
S
M
Normal Range: Serum Creatinine(0.61.4)mg/dl.
Creatinine Clearance:(80-120)ml/min.
.