OVERVIEW OF AMINO ACID METABOLISM

ENVIRONMENT ORGANISM

Bio-
Ingested synthesis
Protein
protein
2 3
1
a
AMINO
ACIDS
b
c c
Degradation Purines
(required) Pyrimidines
Porphyrins
Carbon
Nitrogen
skeletons
(ketogenic) (glucogenic)
Urea Used for
pyruvate
energy α-ketoglutarate
acetoacetate
acetyl CoA succinyl-CoA
fumarate
oxaloacetate
 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 it io n a lly E s s e n t ia l N u t r it io n a lly N o n e s s e n t ia l
- - - - - -- - - -- - - -- - - -- - - -- - - -- - - -- - - -- -- - - - - -- - - -- - - -- - - -- - - -- - - -- - - -- -
A r g in in e a A la n in e
H is tid in e A s p a r a g in e
I s o le u c in e A s p a r ta te
L e u c in e C y s te in e
L y s in e G lu ta m a te
M e th io n in e G lu ta m in e
P h e n y la la n in e G ly c in e
T h r e o n in e P r o lin e
T r y p to p h a n S e r in e
V a lin e T y r o s in e
- - - - - -- - - -- - - -- - - -- - - -- - - -- - - -- - - -- -- - - - - -- - - -- - - -- - - -- - - -- - - -- - - -- - -
a “
N u tr itio n a lly s e m ie s s e n tia l.” S y n th e s iz e d a t r a te s
in a d e q u a te to s u p p o r t g r o w th o f c h ild 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

CO2
Glycine
Aspartate
(amine) 6 7
5 N
1 N
8 N10-Formyl-FH4

2
N
4 N
10
N -Formyl-FH4 3
9

Glutamine (amide)
 Summary and Regulation

Ribose-5-phosphate

5-Phosphoribosyl-1-pyrophosphate (PRPP)
⊖ ⊕
⊖ ⊖
5-Phosphoribosylamine

IMP
⊖ ⊖

Adenylosuccinate XMP

AMP GMP
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.
Cytosine (C) Uracil (U) Thymine (T)

Major Bases
 Sources of the atoms of the pyrimidine ring:

Glutamine 4
3 5
N
Aspartate
2 6

CO2 N
1
DNA and RNA Degradation
“Salvage Pathway” for Purines
(~90%)

Lesch-Nyhan Syndrome
Degradation of Purines
(~10%)
 Allopurinol
Inhibits xanthine oxidase

X
Hem
e
Structure

N
Pyrrole
Porphyrias
 hemoglobin

heme globin

Fe
(reutilized) degraded free amino
(bilirubin) acids
 Heme
Reticuloendothelial
Biliverdin
system
Unconjugated bilirubin

Unconj.bilirubin/
Systemic circulation
albumin complex

Kidney

Unconj. bilirubin Hepatocytes

Bilirubin
urine diglucuronide

Bilirubin diglucuronide
Stercobilins Urobilinogen Bilirubin

Large intestine Small intestine

 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 blood
4) Neonatal “physiological jaundice”
-- immature hepatic system of the newborn:
 uptake, conjugation, excretion of
bilirubin