OVERVIEW OF METABOLISM
TYPE 2 GSD = Pompes disease
df @ -1,4-glucosidase (acid maltase) @ All organs (enzyme is in lysosomes).
Progressive muscle weakness.
Breathing and feeding difficulties.
Hyporeflexia or areflexia due to glycogen accumulation in spinal motor neurons.
Cardiomegaly leading to congestive heart failure
death before the age of 2
Galactitol
Galactose
Non-reducing
End
Non-reducing
End
(4-Glu-1)~(4-Glu-1)~(4-Glu-1)~(4-Glu-1~OH)
(4-Glu-1)~(4-Glu-1)~(4-Glu-1)~(4-Glu-1~ O
Non-reducing
End
(4-Glu-1)~(4-Glu-1)~(4-Glu-1)~(4-Glu-1~OH
HO~4-Glu-1~ O
Non-reducing
End
The transferase activity removes the terminal 3 glucose residues of one branch
and attaches them to a free C-4 end of a second branch.
(4-Glu-1)~(4-Glu-1)~(4-Glu-1)~(4-Glu-1)~(4-(4-Glu-1)~(4-Glu-1)~(4-Glu-1)
The glucose in -(1,6)-linkage at the branch is then removed by the action of glucosidase.
This glucose residue is uncharged
+ Glucose
-Ketoacids
Amino Acids (NH3)
CO2 + PEP
UDP-GAL-4-EPIMERASE
Non-reducing
End
Glucose
Pyruvate
Alanine (NH3)
Glu(NH3)
-KetoGlu
NH4 + CO2
NH2
C Carbamoyl Phosphate
OPO3
Liver Mitochondria
Cytoplasm
MALATE-DH
Ornithine
UREA
CYCLE
Urea
H2O
DHF
Transamination
PDH
CO2 + ATP
Acetyl-CoA
PYRUVATE
CARBOXYLASE
Mg
HIGH
ATP + Acetyl-CoA
State favors the
PC Reaction > PDH Rxn
in the liver
ATP
Acetyl-CoA
NADH
Phenylalanine
Aceto-Acetyl-CoA
Acetyl-CoA Isoleucine
Leucine
Lysine
Tryptophan
Tyrosine
ATP
CITRATE
SYNTHASE
ADP + pi
NAD
Asp + aKG Glu + OAA
cis-aconitate
TCA
Fumarate
Fumerate
Phenylalanine / Tyrosine
Succinyl-CoA
NADH
ATP
Succinyl-CoA
CO2 + NADH
-KG
GLUTAMATE-DH
NADH
NH4
Glutamate Derivatives
Heme
NAD
+Fe
Proto-Porphyrin
Co-Pro-Porphyrinogen
Uroporphyrinogen III
IPP + DPP
GPP + IPP
FPP + FPP
Squalene
Cholesterol
TRANSAMINASES
+ Ergosterol
Hormones
Bile Acids
VitimainD
OH~ C3~Carbon
OH~ C3
Sphingosine
|
OH~ C2
|
OH~ C1
~Carbon Chain
~Carbon Chain
Glycerophosphlipids
C3 ~ester
|
C2 ~ester
|
C1~OPO3
Chain
NH2~ C2
|
OH~ C1
OH~ C3~Carbon
Chain
|
C2 ~amide~Carbon Chain
Sphingomyelins
OH~ C3~Carbon
Chain
~Carbon Chain
~Sugar
Glycophinolipids
|
C2~amide
|
C1
OH~ C3~Carbon
Ceramides
|
C2 ~amide
|
C1~OH
Chain
~Carbon Chain
Cyclicization
~Choline
|
C1~OPO3
~Choline
KetoAcid + Glu
Glutamine
To Urea
Cycle
CO2 + NADH
+
Glycine
ALA SYNTHETASE
ALA
(Regulated Step)
-Amino-Levolinic Acid (ALA) Mitochondria
Cytoplasm
Porphobilinogen
Pre-Uro-Porphyrinogen
TERTRAHYDROBIOPTERIN
*Albinism
here
Homogentisate
*PKU here
fumarate
TCA
Isocitrate
KG-DH
GTP + CoA
Malonyl-CoA
ISOCITRATE-DH
+ Acetyl-CoA + 2NADPH
Inhibits PFK
Citrate Citrate
favoring Gluconeogensis
OAA
FADH2
Arginine
+ ADP
CYSTATHIONE
SYTHASE
NADH MALATE-DH
Malate
Fumerate
ATP +
ATP + CO2
NADH
Malate
Argino-Succinate
OT
(Reducing End
with a free OH)
to UREA Cycle
NH4
Oxidative Deamination
OAA
Citrulline
UDP-Gal
(Reducing End
with a free OH)
GDP
PEP-CARBOXYLASE
GTP
Aspartate
Glu-1P PHOSPHOGLUCOMUTASE
GAL-1P
URIDYL0TRANSFERASE
OPPiO-Uridine
6OH
GLUCOSE
ALANINE CYCLE
ORNITHINE
TRANSCARBAMYLASE
Ornithine + Carbomyl Phosphatate Citrulline
HEXOKINASE
NUCLEOTIDE
PRECURSOR
G3P
(4-Glu-1)~(4-Glu-1)~(4-Glu-1)~(4-Glu-1)~(4-(4-Glu-1)~(4-Glu-1)~(4-Glu-1)
Gal-1P
4-Glu-1-
(4-Glu-1)~(4-Glu-1)~(4-Glu-1)~(4-Glu-1~OH)
(Reducing End
with a free OH)
ADP
+ ATP GALACTOKINASE
(Reducing End
with a free OH)
@ Myophosphorylase @ Muscle.
PHOSPHORYLASE dfMuscle
weakness and cramps after exercise
PHOSPHOGLUCOMUTASE
G6P
(4-Glu-1)~(4-Glu-1)~(4-Glu-1)~(4-Glu-1~OH)
(4-Glu-1)~(4-Glu-1)~(4-Glu-1)~(4-Glu-1~ O
pi + Glucose
G6-PHOSPHATASE
#1
H2O +
T
G6P
UDP-Glucose
GLUCOSE 1P
#2 PHOSPHO-GLUCOSE ISOMERASE
URIDYL TRANSFERASE
+
Fructose
GLYCOGEN SYTHASE +
pi
+
F6P ATP
(4OH-Glu-1)~(4-Glu-1)~(4-Glu-1~OH)
F1P
(F26Bisphosphatase) [cAMP] Glucagon
= F6P, AMP, F26BP
F1,6,BISPHOSPHATASE #3 PFK PFK
PFK = ATP, Citrate
ALDOLASE B
1 ATP Used (Net = -2) Glucagon/cAMP inhibit PFK
F2,6BP AMP F1,6BP
(F26Bisphosphatase)
DHAP
+
Glyceraldehyde
+ NADH Glycerol + NAD
TRIOSE
KINASE
#4 ALDOLASE
TRIOSPHOSPHATE ISOMERASE
Hb
NAD G3P #5 TPI DHAP
GLYCEROL KINASE
G3P
METHEMOGLOBIN REDUCTASE #6 GLYCERALDEHYDE-3-PHOSPHATE DH
G3P Serine
Glycine
CO2 + NH4
1NADH Produced x2 = 2NADH
Met-Hb
NADH 1,3DPG
N5N10-methylene
THF N5N10-methylene
THF
THF
23BPG DIHYDRO-GLYCERO-MUTASE
+H2O
THF
MUSCLE
#7
PHOSPHO-GLYCERATE
KINASE
3PG
DIHYDROFOLATE
REDUCTASE
via SAM CH3
TTMP
#8 PHOSPHO-GLYCERO-MUTASE
LIVER
to Muscle
*MTX,
METHIONINE
Methionine
Homocysteine + Serine + B6
Cystathione Cysteine
Alanine (NH3)
Glutamate (NH3)
SYTHASE
2PG
Glucose
Vit-B12
dTTP
#9
ENOLASE
THF
CH3-THF
Pyruvate Gluconeogenesis
aKG
PEP
PK = F1,6BP activate
#10 PYRUVATE KINASE PK = Alanine + cAMP Glucagon inhibit favoring Gluconeogensis
1 ATP Produced x2 = 2ATP (net = +2ATP)
Ala, Cys, Gly, Ser, Thr Pyruvate + NADH LACTATE-DH Lactate + NAD
ALDOSE REDUCTASE
Non-reducing
End
G6P
2GSH + HOOH
NADP + 2GSH
oxidative
G6P-DH
Glutathion Reductase Scavanging
phase
NADPH + GS-SG
GS-SG + 2H2O
6-Phospho-gluconolactone
GLUCONOLACTONASE
6-Phospho-gluconate
NADP
6PHOSPHO-GLUCONATE-DH
NADPH
R5P
( xylulose )
R5P-ISOMERASE R5P-EPIMERASE
R5P
TRANSKETOLASE
TRANSALDOLASE non-oxidative
TRANSKETOLASE phase
G3P + F6P
FRUCTOKINASE
Essential AAs
PVT TIM HALL
Phe
Val
Thr
Trp
Ile
Met
His
Arg
Leu
Lyse
+ Glutamate
Ornithine + KG
UREA CYCLE
Non-Essential AAs
Ser, Cys, Gly
Ala
Asp, Asn
KG + NH4 + NADPH + H
Glu, Arg, Pro
Tyr
Non-Essential AAs
3PG --> Ser Cysteine Gly
Pyruvate --> Ala
AKG --> Glu, Arg, Pro
Phe --> Tyr
OAA --> Asp --> Asn
Glutamate Derivatives
Glycine
Arginine
Histidine
Prolone