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BIOC 460 DR. TISCHLER
LECTURE 39
NITROGEN BIOSYNTHETIC PATHWAYS
OBJECTIVES
1. Outline the pathways for synthesis of the following
nonessential amino acids by identifying the primary
source of the carbons and the nitrogen for their synthesis
(alan, arg, asp, glu, gln, and tyr) in humans.
1. General role of cofactors-derived from folic acid and how
these are important in metabolism of ser, gly, met and cys
1. Discuss significance of S-adenosylmethionine in "onecarbon" metabolism
OBJECTIVES (cont.)
4. Identify two specific cofactor forms of vitamin B12 and list
the amino acids whose metabolism depends on each form.
5. Concerning heme synthesis:
a) describe the reactions involved in the formation of
porphobilinogen
b) discuss the key features of its regulation
c) explain why lead poisoning would affect the oxygen
carrying ability of the blood.
6. List the steps in the catabolism of heme to conjugated
bilirubin and identify the general condition associated with
the accumulation of bilirubin in the body.
-ketoglutarate
+ NH3
NAD(P)H
D
pyruvate
A
alanine
NH3 +
CO2 +
ATP
+ carbamoyl
phosphate
ADP + Pi
NAD(P)+ NH3 +
ATP
citrulline
+aspartate
E
glutamate
glutamate
-ketoglutarate
ornithine
glutamate
argininosuccinate
glutamine
oxaloacetate
C
aspartate
phenylalanine
F
arginine
B
tyrosine
Figure 1. Synthesis of the nonessential amino acids
alanine (A), arginine (B), aspartate (C), glutamate (D),
glutamine (E), and tyrosine (F).
aspartate
asparagine
glutamate
glutamine
3-phosphoglycerate
serine
NADH + -ketoglutarate
+ Pi
NAD+ + glutamate + H2O
serine
THF
glycine
CH2-THF
NH3 + CO2
THF
+ NAD+
CH2-THF
+ NADH
glycine synthase
Figure 2. Synthesis of the nonessential amino acids
asparagine, serine, glycine. CH2-THF is methylene
tetrahydrofolate
Cysteine
CH
CH33 group
donation
Cystathionine
adenosine
S-Adenosylmethionine
Homocysteine CH3B12
CH3
THF
Methionine synthase
ATP
Methionine-CH
CH3 3
Hydroxy B12
N5-CH
CH33 THF
Figure 3. Metabolism of CH3-THF, CH3-Cbl, met and cys.
Table 1. Summary of the roles of folate and
cobalamin in nitrogen metabolism
Cofactor
Vitamin
precursor
Methyl-cobalamin
Adenosyl-cobalamin
Cobalamin
(vitamin B12)
Methylenetetrahydrofolate
Methyltetrahydrofolate
Tetrahydrofolate
Role
methionine
metabolism
isoleucine/valine
metabolism
serine/glycine
metabolism
Folic acid
methylcobalamin
formation
thymidine
biosynthesis
Succinyl CoA +
Glycine

-Aminolevulinate
synthase
pyridoxal
phosphate
-Aminolevulinic acid
-Aminolevulinic acid
(two molecules)


HEME
Fe2+
Protoporphyrin IX
Ferrochelatase
Pb-sensitive
Coproporphyrinogen III
MITOCHONDRIA
CYTOPLASM
Aminolevulinic acid
dehydratase
zinc-containing enzyme
Pb-sensitive
Coproporphyrinogen III
Uroporphyrinogen III
Porphobilinogen
4 molecules
Figure 4. Pathway for synthesis of heme
combine
REGULATION OF HEME SYNTHESIS:
Heme:
inhibits activity of pre-existing -ALA synthase
diminishes transport of -ALA synthase from cytoplasm
to mitochondria after its synthesis
represses the production of -ALA synthase by regulating
gene transcription.
TEETH FROM PATIENT WITH PORPHYRIA DISORDER
PATIENT WITH PORPHYRIA DISORDER
BLOOD
CELLS
Hemoglobin
Stercobilin
excreted in feces
Globin
Heme
O2
Heme
oxygenase
CO
Biliverdin IX
NADPH
Biliverdin
reductase
NADP+
Bilirubin
(waterinsoluble)
Urobilin excreted
in urine
Urobilinogen
formed by bacteria
KIDNEY
reabsorbed
INTESTINE
into blood
via bile duct to
intestines
Bilirubin diglucuronide
(water-soluble)
2 UDP-glucuronic acid
Bilirubin
LIVER
(waterinsoluble)
via
blood to
the liver
Figure 5. Catabolism of hemoglobin
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