Ehlers-Danlos Syndrome types
Ehlers-Danlos syndrome: faulty collagen synthesis causing:
1) Hyperexensible skin
2) Easy bruising/bleeding
3) Hypermobile joints
10 different types
Types 1 and 2: affects type V collagen. Easily bruised skin.
Type 3: hypermobility, type III? collagen affected.
Type 4: vascular. Affects type III collagen.
Energy Metabolism Anabolism Pathways
Enzymes active when dephosphorylated
Enzymes active when dephosphorylated:
· Pyruvate Dehydrogenase
· PFK-2
· Pyruvate Kinase
· Glycogen synthase
Galactosemia: mild (Galactokinase), severe (Galactose-1-phosphate uridyltransferase)
Galactosemia (mild, severe)
Lactose (galactose and glucose disaccharide) à Galactose à Galactose-1-Phosphate à Glucose-1-phosphate
Galactose is converted into Galactose-1-phosphate by Galactokinase (which if deficient may result in mild Galactosemia).
Galactose-1-phosphate is converted to Glucose-1-phosphate by Galactose-1-phosphate uridyltransferase (which if deificient will result in severe galactosemia: mental retardation, cataracts, hepatosplenomegaly).
Lactose (glucose + galactose) à 1 Glucose + 1 galactose [lactase]
1 Galactose à Galactose-1-phosphate [galactokinase]
Galactose-1-phosphate à Glucose-1-phosphate [galactose-1-phosphate uridyltransferase]
Glucose-1-phosphate à Glucose-6-phosphate [phosphoglucomutase]
Glycogenolysis and Glycogen synthesis -- Glycogen phosphorylase
Glycogenolysis and Glycogen synthesis
Glycogen phosphorylase:
Glycogen àààGlucose-1-phoshateàGlucose-6-phosphate
Gluocse-1-phosphateà UDP-GlucoseàGlycogen
UDP-GlucoseàUDP-GalactoseàUDP-Gluocose
· Glycogen is broken down into glucose-1-phosphate by the enzyme glycogen phosphorylase.
· This enzyme is active when phosphorylated and inactive when dephosphorylated.
· It can also be activated allosterically (by AMP). AMP is increased in anoxia and activates glycogen phosphorylase without phosphorylating it.
· Ca++ will also activate GP.
· GP is inhibited by ATP (increased in a well fed state when there is plenty of G6P… G6P instead will stimulate production of Glycogen from UDP-Glucose).
· The enzyme’s phosphorylation is done by Phosphorylase Kinase.
· Phophorylase Kinase is phosphorylated (activated by Protein Kinase A).
· Gs receptors are stimulated by hormones like epinephrine (a1, a2, b1, b2) and glucagon (Glucagon receptor in hepatocytes, a Gs membrane receptor).
· Gs receptor activated (by B1, B2, D1, H2, V2) à Adenylyl cyclase activated à make cAMP out of ATP à cAMP activates Protein Kinase A à PKA then activates Phosphorylase kinase à which then phosphorylates the Glycogen phosphorylase.
Glycolysis and Gluconeogenesis, HMP shunt
Glycolysis and Gluconeogenesis
1 Glucose à glucose-6-phosphate [glucokinase/hexokinase] , <à fructose-6-phosphate
requires ATP. Reverse reaction done by glucose-6-phosphatase (deficiency of which leads to Von Gierke’s). An impaired ability to make glucose in the liver from either gluconeogenesis or break down glucose from glycogen.
Hexose monophosphate shunt
· a way to generate NADPH (first 3 steps which are oxidative and make 2 NADPH) which is used for anabolic process (lipid and nucleic acid synthesis) and to reduce oxidative stress (with glutathione)
· also makes 5 carbon sugars (pentoses) – which are used in making nucleotides and nucleic acids
· takes place in cytosol
· an alternative to glycoslysis (which makes NADH)
HMP shunt:
glucose-6-phosphate à 6-phosphogluconolactone, NADPH à6-phosphogluconateà x, NADPHà Ribulose-5-phosphate àààFructose-6-phosphate à fructose-1,6-bisphosphate
· the first step done by G-6PD (if deficient, get hemolytic anemia because RBCs depend on glycolysis alone to metabolize glucose)
Glycolysis continued……
Fructose-6-phosphate à Fructose-1,6-bisphosphate
(is the rate-limiting step in glycolysis)
· catalyzed by PFK-1 (phosphfructokinase-1)
another possibility for F-6-P:
Fructose-6-phosphate à fructose-2,6-BP
· catalyzed by PFK-2 (which is active when dephosphorylated, in liver)
· F-2,6-BP is the most potent activator of PFK-1
Glycolysis continued…
Fructose-1,6-bisphosphateà Glyceraldehyde-3-P, DHAP à 1,3-bis-phosphoglycerateà 3-phosphoglycerateà 2-phosphoglycerate à Phosphoenolpyruvate à Pyruvate à Acetyl-CoA à
Irreversible Reactions of Glycolysis
Irreversible Reactions of Glycolysis:
· Hexokinase/Glucokinase (in liver)
· PFK-1
· Pyruvate Kinase
· Pyruvate Dehydrogenase
TCA cycle
TCA cycle (Kreb’s cycle)
Citrate à Isocitrate à a-Ketoglutarate à Succinyl-CoA, NADH à Succinate, GTP à Fumarate, FADH2 à Malate à Oxaloacetate, NADH à Citrate
Urea Cycle
Urea Cycle
NH4+CO2 à Carbamoyl phosphate
(rate limiting step, CPSI)
Carbamoyle phosphate + Ornithine à Citrulline à Arginosuccinate à Argnine, Fumarate (which goes to TCA cycle)
Arginine + H2O à Urea , Ornithine
(reaction done by Arginase, an enzyme found only in the liver)