OVERVIEW OF AMINO ACID METABOLISM
ENVIRONMENT ORGANISM
Ingested protein
Bio- synthesis Protein
AMINO ACIDS
Nitrogen Carbonskeletons
Urea
Degradation (required)
1 2 3
a
b
PurinesPyrimidinesPorphyrins
c c
Used for energy
pyruvateα-ketoglutaratesuccinyl-CoAfumarateoxaloacetate
acetoacetateacetyl CoA
(glucogenic)(ketogenic)
A m in o A c id R e q u ir e m e n t s o f H u m a n s - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - N u t r i t io n a l ly E s s e n t ia l N u t r i t io n a l ly N o n e s s e n t ia l - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
A r g in in e a A la n i n e H i s t id i n e A s p a r a g i n e I s o l e u c in e A s p a r t a te L e u c in e C y s t e i n e L y s i n e G lu ta m a te M e th io n in e G lu ta m i n e P h e n y la l a n i n e G l y c i n e T h r e o n in e P r o l in e T r y p to p h a n S e r in e V a l in e T y r o s in e
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - a “ N u tr i t io n a l l y s e m ie s s e n t ia l .” S y n t h e s iz e d a t r a te s i n a d e q u a te to s u p p o r t g r o w t h o f c h i ld r e n .
NITROGEN BALANCE
Nitrogen balance = nitrogen ingested - nitrogen excreted
(primarily as protein) (primarily as urea)
Nitrogen balance = 0 (nitrogen equilibrium)
protein synthesis = protein degradation
Positive nitrogen balance
protein synthesis > protein degradation
Negative nitrogen balance
protein synthesis < protein degradation
TRANSAMINATION
UREA CYCLE
mitochondria
cytosol
Function: detoxification of ammonia (prevents hyperammonemia)
FATE OF THE CARBON SKELETONS
Carbon skeletons are used for energy.
Glucogenic: TCA cycle intermediates
or pyruvate (gluconeogensis)
Ketogenic: acetyl CoA, acetoacetyl CoA,
or acetoacetate
Purine and
Pyrimidine Metabolism
Major Bases
Source of each atom in the purine ring
N
N
N
N
9
1 8
7 6 5
4
3
2
Glycine
N10-Formyl-FH4
N10-Formyl-FH4
Aspartate (amine)
CO2
Glutamine (amide)
Ribose-5-phosphate
5-Phosphoribosyl-1-pyrophosphate (PRPP) ⊖ ⊕ ⊖ ⊖
5-Phosphoribosylamine
IMP
Adenylosuccinate XMP
AMP GMP
⊖⊖
Summary and Regulation
Inhibition of Purine Biosynthesis by the Antitumor Agent, 6-Mercaptopurine
1) 6-Mercaptopurine is converted to a nucleotide.
2) The nucleotide inhibits purine biosynthesis at steps 2, 12a, 12b, and 13a.
Major Bases
Cytosine (C) Uracil (U) Thymine (T)
N
N
2
1
3
4
5
6
Aspartate
CO2
Glutamine
Sources of the atoms of the pyrimidine ring:
DNA and RNA Degradation
“Salvage Pathway” for Purines(~90%)
Lesch-Nyhan Syndrome
Degradation of Purines(~10%)
AllopurinolInhibits xanthine oxidase
X
X
Heme
N
Pyrrole
Structure
Porphyrias
hemoglobin
globinheme
free amino acids
degraded (bilirubin)
Fe (reutilized)
Heme
Biliverdin
Unconjugated bilirubin
Reticuloendothelial system
Unconj.bilirubin/albumin complex
Systemic circulation
HepatocytesUnconj. bilirubin
Bilirubin diglucuronide
Small intestineLarge intestine
Bilirubin diglucuronideBilirubinUrobilinogenStercobilins
Kidney
urine
HYPERBILIRUBINEMIA
-- elevated bilirubin in serum (above 1 mg/dL)
-- can be conjugated or unconjugated or both depending on the situation
-- elevated bilirubin can diffuse into tissues, making them appear yellow (jaundice)
HYPERBILIRUBINEMIA
Clinical Consequences:
-- Conjugated hyperbilirubinemia: benign
-- Unconjugated hyperbilirubinemia: benign at concentrations < 25 mg/dL (albumin capacity)
-- At concentrations >25 mg/dL, unconjugated bilirubin is free (uncomplexed) and can enter the brain.
bilirubin encephalopathy (kernicterus)
Causes of JAUNDICE
1) Hemolytic anemia
-- destruction of erythrocytes
2) Hepatitis or cirrhosis
-- conjugation and excretion of bilirubin
3) Bile duct obstruction
-- conjugated bilirubin not delivered to intestine;
it backs up, spills over into the blood4) Neonatal “physiological jaundice”
-- immature hepatic system of the newborn:
uptake, conjugation, excretion of bilirubin
Top Related