Aminoacid metabolism

-2
Dr. S.Chakravarty MD

Metabolism of Sulphur containing

Aminoacids:
Metabolic function of cysteine:

1. Disulphide linkages in Proteins

2. Formation of Glutathione (functional group is sulphur of cysteine)
Glutamyl cysteinyl-Glycine
3. Active site of many enzymes
4. Miester cycle transport of amino acids
5. Maintain RBCs membrane integrity Glutathione
6. Formation of Taurine formation of Bile acids and neurotransmitter
7. Detoxification of drugs - Glutathione s-transferase

Methionine
Formation of SAM: Methyl Donor
Methionine +
ATP

S-adenosyl
Methionine (SAM)

Methyl Acceptor

Methylated Product

Guanido acetic acid

Creatine

Nor-epinephrine

Epinephrine

Epinephrine

Metanephrine

Ethanolamine

Choline

Acetyl serotonin

Melatonin

Spermidine

Spermine

Branched
Ch AA
Aromatic
AA

S-containing

Catabolism
Methionin
of cysteineMethionine adenosyletransferaseATP
and
methionine S- Adenosyl Methionine
(SAM)
Methyl transferase

TH
F

Acceptor

CH3-acceptor

S- Adenosyl
Homocystiene (SAH)
Adenosine

Serin
Cystathionine

e
synthase
TCA
cycle

Pyruvat

Homocystei
ne
B6(PLP)

Cystathioni
ne
Cystathionin
B6
ase
Cysteine +

Homocysteine
methyl
Transferase

B12

Very
Important

Methyl
THF
Propionyl CoA

TCA
cycle

Alpha-keto

Oxidation of odd chain fatty acids

Oxidation of fatty acid with odd no. of carbon
atom yields acetyl CoA + Propionyl CoA( Enters
TCA as Succinyl Co-A).Thus this portion of odd
chain fatty is glucogenic.

Disorders of sulfur containing

aminoacids

Cystinuria :
Autosomal recessive

Defect in intestine and renal

absorption of Cysteine, Ornithine,
Lysine, Arginine (COLA)
Cystine stones hexagonal crystals
Nephrolithiasis and Urolithiasis

Cystinosis
Lysosomal disorder
Defective carrier mediated transport of cysteine Increased lysosomal
cysteine lysosomal cystine appears to amplify and alter apoptosis in
such a way that cells die inappropriatelyRenal failure(Fanconis
syndrome )
In order of decreasing severity the following are the types of cystinosis: nephropathic cystinosis
intermediate cystinosis,
non-nephropathic or ocular cystinosis

Renal failure, vit-D resistant rickets, acidosis, polyuria, photophobia

(fanconi syndrome)
Liver, cornea, spleen, kidney, bone marrow involved crystal formation

Congenital Homocystinuria
Marfanoid habitus
Type

Defect

Treatment

Cystathionine synthase

Cysteine,
Methionine
and
Pyridoxine

II

N5, N10 Methylene

THF reductase

III

IV

Homocyeteine methyl
transferase
(methionine
synthase)
Decreased absorption
of B12 from intestine

Folate

Folate

Folate and
B12

Genetic
Defect

Lipid
peroxidation

S-S linkages in
Proteins

DIET

Homocystei
ne
Activates
Hageman
factor
Platelet
aggregatio
n

Atherosclero
sis

Homocysteine
Thiolactone

Oxidized LDL
Endocytosis
by
Macrophages

Differences
Marfan syndrome

Congenital
Homocysteinuria

Autosomal dominant

Autosomal recessive

Lens dislocation is
upwards and outwards

Lens dislocation is
downwards and inwards

Aortic incompetance /
valvular heart disease

Ischemic heart disease

due to thromboembolic
phenomenon

Mental retardation
absent

Mental retardation
common

Acquired Homocysteinuria
Vitamin deficiencies
INCREASED HOMOCYSTEINE , INCREASED
B6
METHIONINE
B12
INCREASED HOMOCYSTEINE
DECREASED METHIONINE
FOLATE
No Marfanoid habitus
Reversible
HOW TO DISTINGUISH ?

SER,
GLY

Kaplan USMLE step 1 lecture

notes

x
x
x

MEGALOBLAST
IC ANAEMIA

MEGALOBLASTS ?
DNA synthesis is impaired, the cell cycle cannot progress from the G2 growth st
tosis (M) stage. This leads to continuing cell growth without division, which
ts as macrocytosis.

Accumulation
of ODD chain
fatty acids in
neurons
Toxicity from
mehylmalonate

Kaplan step 1 lecture

Metabolism of Basic amino acids

1. Histidine :
Imidazole ring Basic amino acid
Formation of Histamine
Physiological buffer pKa of 6.8

Metabolism of Histidine
Histidine
decarboxylas
e

Histamin
e

histamina
se

Histidin
Histidas
e
e

Urocanat
Urocanas
e
e

FIGLU

Imidazole acetic
acid

Glutamat
e
Alpha keto
Glutarate

FIGLU formiminoglutamic acid

THF

Measure in
Folic acid
deficiency

Formimino
THF

TCA
cycle

Histidinemia :
Decreased histidase activity:
Histidine undergoes transamination to form
imidazole pyruvate, imidazole lactate and
imidazole acetate.
Mistaken for phenylketonuria
Mental retardation
Diagnosis: sweat urocanate levels decreased
FIGLU excretion decreased.

2. Arginine
Formation of urea
Synthesis of Nitric oxide vasodilator
Synthesis of Creatine phosphate and
Creatinine
Synthesis of Polyamines spermine and
spermidine cell growth and
proliferartion .

Catabolism of Arginine
Arginin
e
Urea

Arginas
e

Ornithi
ne
Glutamat
e

Alphaketoglutar
ate

TCA
cycle

Metabolism of Glycine
Formation of Heme: first step
Formation of Glutathione
Formation of Bile salts Glycocholic acid
Conjugation Hippuric acid (Hippuric acid)
C4, C5, N7 of Purine Ring formation

Catabolism of Glycine

Primary
hyperoxaluria
-1
(-)

Alanine
glyoxylate
Aminotransferas
e

glyoxylate
reductase

(-)

Primary
hyperoxaluria
-2

Glycin
e
Pyruvat

PL
P

Ethylene Glycol
(Antifreeze)

e
Alanine

Glyoxylat
e
Glycolate

Oxalic
acid

Calcium oxalate

Glycolic
acid
Certain Sugars
and aa

Causes for increased oxalate stone

formation
Green leafy vegetables oxalates
Ascorbic acid Vit C
Ethylene glycol poisoning
antifreeze
Primary oxaluria Type 1 and 2
Calcium oxalate stone
formation
Kidney damage Renal

Formation of Creatine and Creatinine

Arginine +
Glycine
Diagnosis of
various Muscle
disorders , Acute
Myocardial
infarction

Guanidoacet
ate

Creatine Phospho
kinase

Creatin
e

Creatine
phosphate

Kidney and Pancreas

mitochondria

SAM Liver
SA
H

Urine

Creatini

 A 56 year old man is being evaluated for macrocytic

anaemia. He was severely malnourished.Both
homocysteine and methyl malonate were elevated in
his blood and urine , and the transketolase level in his
RBC was low.
What is the best evidence cited that the anaemia is
due to B12 deficiency?
A. Macrocytic anaemia
B. Elevated methyl malonate
C. elevated homocysteine
D. decreased homocysteine
E. severe malnutrition

 A 49 year old man has ectopia lentis and

comes to ER with deep vein thrombosis .He
has a normal hematocrit and RBCs are
normocytic normochromic.
A mutation of genes coding for which of the
following is the cause ?
A. Cystathionine synthase
B. Homocysteine methyl transferase
C.Fibrillin
D.Lysyl oxidase]
E. FACTOR VIII

 Amino acid analysis of this patients

plasma would most likely reveal an
abnormally elevated level of
A. Lysine
B.Leucine
C. methionine
D. Ornithine
E. Cysteine