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BioChem Flow Chart

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by

Samir Al-Ayoubi

on 20 March 2015

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Transcript of BioChem Flow Chart

Acetyl CoA
Citrate
Isocitrate
a-Ketogluterate
Succinate
Fumerate
Malate
OAA
Pyruvate
Fluorocitrate
Aconitase
Citrate
Synthase
Isocitrate
DH
Succinyl
CoA

α-Ketoglutarate
DH
Succinate
Thiokinase
Succinate
DH
Fumerase
Malate
DH
Succinyl CoA, Fatty Acyl CoA
ATP, NADH
Ca 2+, ADP
TCA
CYCLE
MITOCHONDRIAL
MATRIX
(PERIPHERAL TISSUE)

Fatty Acid
Fatty acyl CoA
synthetase
(thiokinase)
Fatty Acyl CoA
CPT-I
Carnitine
Acyl Carnitine
Acyl Carnitine
Carnitine
Translocase
CPT-II
Fatty Acyl CoA
Carnitine
Malonyl CoA
AMP + PPi
Pyruvate
PDH
GLYCOLYSIS
&
GLUCONEOGENESIS

β-adrenergic
Receptor
Adenylyl
Cyclase
Gαs
GDP
Gαs
cAMP
Protein
Kinase A
TAG
Hormone
Sensitive
Lipase
(Active)
Glycerol
Hormone
Sensitive
Lipase
(Inactive)
Monoacylglycerol
acyl CoA
monoacylglycerol
acyl transferase
Phosphoenolpyruvate
Pyruvate
Kinase
Enolase
2-phosphoglycerate
ATP, Alanine, Glucagon
F 1,6 BP
Phosphoglycerate
mutase
3-phosphoglycerate
Phosphoglycerate
kinase
1,3-bisphosphoglycerate
NADH
NAD+
ADP
Glyceraldehyde 3-phosphate
Dihydroxyacetone Phosphate
Glycerol 3 Phosphate
NADH
NAD+
Glycerol 3 phosphate
DH
Lysophosphatidic acid
Phosphatidic acid (DAG phosphate)
1,2 Diacylglycerol (DAG)
H2O
Triacylglycerol
CoA
CoA
CoA
Triosephosphate
Isomerase
Fructose 1,6 bisphosphate
TAG
BIOSYNTHESIS

α-1
adrenergic
Receptor
Epinephrine
or
Glucagon
Epinephrine
Gαq
GDP
Phospholipase C
Gαq
Phospholipase A2
PIP2
IP3
DAG
Protein
Kinase C
Ca 2+
Ca 2+
Arachdonic Acid (ω-6)
Lysophospholipid
Cortisol (corticosteroids)
PGG2
(obligatory precursor)
PGH2
TXA2
PGI2
Prostacyclin
Synthase
Thromboxane
Synthase
(RDS)
Corticosteroids,
Aspirin / NSAIDS,
COX-2 inhibitors,
COX-1
Cyclooxygenase - 1
(constitive)
COX-2
Cyclooxygenase - 2
(nonconstitive)
Aspirin / NSAIDS
(irreversibly binds
acetyl group)
Cytokine (IL-1, TNF)
Endotoxin, Growth Factor,
Tumor Promoter
(Promote
Platelet aggregation,
vasoconstriction)
(Inhibit
Platelet aggregation,
vasodialtion)
PROSTAGLANDIN,
THROMBOXANE,
LEUKOTRIENE,
SYNTHESIS
G-PROTEIN
COUPLED
RXN

5-HPETE
LOX
5-LIPOXYGENASE
LTA-4
LTE-4
(Cysteine residues)
(SRS-A inc. vascular
permeability
bronchoconstriction
vasoconstriction)
CPT-II
Deficiency
(systemic)
CPT-II
Deficiency
(myopathic)
(16+C chains)
NADH
NAD+
CO2
CO2
NADH
NAD+
ATP, NADH
ADP, Ca 2+
ATP, GTP, NADH,
Succinyl CoA
Ca 2+
GDP
TPP
FAD
FADH2
Malonate, OAA
ADP, Pi, Succinate
NADH
NAD+
CO2
Pyruvate DH
Dihydrolipoyl
Transacetylase
Dihydrolipoyl DH
TPP
Ca 2+, Insulin,
catecholamine

Acetyl CoA, ATP, NADH
H2O
NAD+
NADH
+CoASH
Citrate
Acetyl CoA
ADP
CoA
OAA
ATP-citrate
Lyase
(Fed state)
Malate
Malic
Enzyme
NADP+
NADPH
CO2
Malat DH
NADH
NAD+
(covalent)
Malonyl CoA
Acetyl CoA
Carboxylase
(Active)
Acetyl CoA
Carboxylase
(Inactive)
AMP-dependent
Kinase (AMPK)
(Active)
Allosteric
regulation
(short term)
Palmitatoyl CoA, Malonyl CoA, Glucagon
Citrate
Covalent
regulation
(short term)
Acetyl CoA
Carboxylase
(Inactive)
Acetyl CoA
Carboxylase
(Active)
Glucagon/Epinephrine
AMP
OR
7 ATP
7 ADP
CO2
Protein
Phosphatase
Insulin
Protein
Kinase A
Protein
Kinase A
Palmitate (16C)
14 NADPH
14 NADP+
Chain elongaton
(adding malonyl CoA)
/ desaturtion (5,6,9 C)
1. Cytochrome b5
2. Desaturase
3. NADPH-cytochrome
b5 reductase
Enoyl CoA
(medium 6-10C)
MCAD
Acyl CoA DH
(long chain 10+C)
(small chain 6-C)
MCAD
Deficiency
OR
OR
FAD
FADH2
H2O
3-Hydroxyacyl CoA
NAD+
NADH
3-Ketoacyl CoA
Acetyl CoA
CoA
Fatty Acyl CoA
Fatty Acyl CoA
β-OX
Propionyl CoA
(odd chain FA)
(even chain FA)
Methylmalonyl CoA
Propionyl CoA
carboxylase
Succinyl CoA
Methylmalonyl
CoA mutase
Vit B12
Biotin
Acetyl CoA
FATTY ACID
SYNTHESIS

(oxidzed β C)
# CYCLES : (nC/2) - 1
Branched Chain
21+ C Fatty Acid
Pristanic acid
19C
Peroxisome
α-OX
Branched chain
20C Fatty Acid
(alternative pathway for
β-oxiaiton disorders)
ω-OX
Dicarboxylic
Acid
(found in urine)
MCAD
Deficiency
Acetoacetyl CoA
(RDS)
(RDS)
Thiolase
CoA
HMG CoA
synthase
(ONLY in
LIVER mitochondria)
HMG CoA
Acetoacetate
Acetone
3-hydroxy butyrate
3 Ketone
Bodies
CO2
(spontaneous)
fruity/nail polish
expiration
Phytanoyl CoA
α-hydroxylase
Zellweger
Refsum
3-hydroxy
butyrate DH
NAD+
NADH
KETOGENEIS
(utilized in skeletal and
cardiac mucle, brain)
HMG CoA
Lyase
Succinyl CoA:
acetoacetate
CoA transferase
(thiophorase)
Succininyl
CoA
Succinate
(ONLY in PERIPHERAL
mitochondria NOT liver)
Fructose 6-phosphte
Glucose 6-phosphate
Glucose
ADP
Hexokinase
OR
Glucokinase
Fructose 6-P
ADP
Phosphoglucose
Isomerase
Phosphofructokinase-1
(PFK-1)
PFK-2
F 2,6 BP
Insulin
Glucagon
Fructose 2,6 bisphosphte
ATP, Citrate, H+
AMP, F 2,6 BP
Insulin
GLUT-4
(adipose & muscle)
GLUT-1

(RBC, Brain)
GLUT-3

(Nervous tissue)
Pyruvate
carboxylase
(Acetyl CoA)
Biotin
ADP
CO2
A
G
A
G
A
G
ADP
ADP
PEP
carboxykinase
Cortisol
Fructose 1,6
bisphosphatase
F 2,6 BP, AMP
Glucose
6-Phosphatase
MALATE
SHUTTLE

(3-Hydroxy-3-methylglutaryl CoA)
(Fed state)
(Fasting state)
(Fasting state)
(Fed state)
(Fed state)
(Fasting state)
AMP-dependent
Kinase (AMPK)
(Inactive)
HMG CoA (6C)
(3-Hydroxy-3-methylglutaryl CoA)
Acetyl CoA
CoA
CoA
Mevalonic Acid (6C)
(mevalonate)
2 NADPH
2 NADP+
Insulin, Low cholesterol (stimulates release of SREBP (inc enzyme synthesis)), Estrogen, Clofibrate
5-pyrophosphomevalonate (6C)
Isopentenyl pyrophosphate (6C)
dolichol & ubiquinone
(Coenzyme Q, for ETC fxn)
(glycoprotein)
3,3-dimethylallyl pyrophosphate (DPP) (5C)
geranyl pyrophosphate (GPP) (10C)
squalene (30C)
protein prenylation
(protein modifiation)
dolichol
ubiquinone
CHOLESTEROL
BIOSYNTHESIS

lanosterol (30C)
Cholesterol
farnesyl pyrophosphate (FPP) (15C)
HMG CoA
reductase
(Active)
AMP-dependent
Kinase (AMPK)
(Active)
Allosteric
regulation
Covalent
regulation
Glucagon/Epinephrine
AMP
OR
Protein
Kinase A
(RDS)
(RDS)
AMP-dependent
Kinase (AMPK)
(Inactive)
HMG CoA
reductase
(Inactive)
HMG CoA
reductase
(Active)
HMG CoA
reductase
(Inactive)
Glucagon
-High cholesterol, LDL (feedback inhibition --> proteolysis of enzyme - ubiquitin system proteosomes)
-Statin drugs (allosteric competative inhibitor, reduces cholesterol but UPREGULATES enzyme synthesis)
(intracellular)
Acyl-CoA
acyltransferase
ACAT
Cholesterol ester
high LDL
(inc LDL receptor -->
LDL endocytosis,
breakdown,
and STORAGE
(for TAG, lipid vitamins,
phospholipid membrane)
(cholesterol STORAGE)
Cholesterol
Cholesterol
esterase
Steroidogenic acute
regulatory protein
(StAR)

Cholesterol
Desmolase
CYP11A1

Pregenolone

(RDS)
Pregenolone

Progesterone
Deoxycorticosterone
3β-hydroxysteroid
DH

21-hydroxylase
(CYP21A2, P450c21)
Corticosterone
11β-hydroxylase
(CYP11B1, P450c11)
17-hydroxypregnenolone

17-hydroxyprogesterone
11-dexoycortisol
Cortisol
Aldosterone
(Z. Glomerulosa)
(Z. Fasciculata)
3β-hydroxysteroid
DH

Dehydroepiandrosterone
(DHEA)
17α-hydroxylase
(CYP17A1, P450c17)
3β-hydroxysteroid
DH

11β-hydroxylase
(CYP11B1, P450c11)
21-hydroxylase
(CYP21A2, P450c21)
Androstenedione
Testosterone
Estrone
Aromatase
(CYP19)
Aromatase
(CYP19)
Estradiol
Dihydrotestosterone
(Z. Reticularis)

deficiency

17α
deficiency
21
deficiency
11β
deficiency
STEROID
HORMONE
SYNTHESIS

(27C)
Cholic acid
7-α-hydroxylase
Cholesterol
Cholic acid
Chenodeoxycholic acid
(Primary Bile acids)
conjugated to
primary bile salt
with
glycine or taurine
taurocholic acid
glycocholic acid
OR
glycochenodeoxycholic acid
taurochenodeoxycholic acid
OR
BILE SALT
SYNTHESIS

(Facilitate digestion by emuslifying TAG)
taurocholic acid
glycocholic acid
OR
glycochenodeoxycholic acid
taurochenodeoxycholic acid
OR
conjugate to
secondary bile
salt via intestinal
bacteria
taurodeoxyocholic acid
glycodeoxycholic acid
OR
glycolithocholic acid
taurolithocholic acid
OR
(Secondary Bile salt)
(Primary Bile salt)
(pKa 6)
(pKa 4)
(pKa 2)
Chylomicron
APO B48
Chylomicron
APO B48
APO C2
APO E
HDL
APO A1
APO C2
APO E
Lecithin
cholesterol
acyltransferase
LCAT
APO A-1
Nascent HDL
HDL 3
HDL 2
Free CE
(for release into
lymph - circulation)
Chylomicron
APO B48
HDL
APO C2
Lipoprotein
Lipase
APO C2
Type I
HL
TAG = 3 FFA + glycerol
Chylomicron
Remnants
APO B48
APO E
CMRR
Chylomicron
Remnant
Receptor
APO E
CAPILLARIES
SR-B1
Scavenger
Receptor B1
ABC
Transporter
Nascent VLDL
APO B100
(for release)
Insulin
VLDL
APO B100
APO C2
APO E
HDL
APO C2
APO E
VLDL
APO B100
APO C2
APO E
IDL
APO B100
APO E
50% IDL
APO C2
HDL
IDL
TAG = 3 FFA + glycerol
Lipoprotein
Lipase
APO C2
Type 4
HL
CAPILLARIES
CMRR
Chylomicron
Remnant
Receptor
LRP
LDLR
APO B48
APO E
APO B100
APO B100
APO E
APO B100
APO E
LDL
APO B100
HDL
APO E
Hepatic
Lipase
Type 3
HL
CAPILLARIES
30% LDL
APO B100
(to circulation)
LDLR
(liver entry)
LIPOPROTEINS
EXTRACELLULAR
(bound to
Heparan
Sulfate)
(bound to
Heparan
Sulfate)
Type 2
HL
CETP
HDL-CE
HDL-TAG
(exchanges CE for TAG)
(to transfer
cholesterol out)
(Hepatic Lipase
and
Phospholipase
activity to get
cholesterol out)
Tangier
disease
TAG
TAG
APO C3
Glucagon
Phosphoprotein
phosphatase
Insulin
(high glucose, after glycogen stores are
maxed,has already made pyruvate and citrate)
(ONLY in
LIVER mitochondria)
Glycerol
Glycerol
kinase
(ONLY in liver)
(Fed State)
Biotin
Biotin
PGE2 - vasodialtion (inflammation)
fEEver
pain
PGF2 - vasoconstriction (inflammation)
CYP11B2
17α-hydroxylase
(CYP17A1, P450c17)
AMP
(bound to
Heparan
Sulfate)
LOX inhibitor
LOX receptor inhibitor
LTB-4
(attracts and activates
neutrophils)
LTC-4
LTD-4
(Secondary-Delayed
response of Mast cells)
Full transcript