Download - CARBOHYDRATE BIOSYNTHESIS
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CARBOHYDRATE BIOSYNTHESIS April 14, 2015
BC368
Biochemistry of the Cell II
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vs. HCl
Chloroplast vesicles isolated in some kind of physiological buffer.
Question 4. See pages 786-787.
Vesicles soaked in pH 4 medium.
Effect of proton ionophore?
Effect of DCMU?
Effect of dark?
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“MY PHILODENDRON ISN’T DOING SO WELL.”
An older philodendron is brought into the nursery in very bad condition. It is seriously etiolated and has not grown well for three months. Although the owner moved to Eastern Pennsylvania from Iowa five months earlier, light levels, humidity, and temperature are essentially similar. You are working at the nursery to help earn extra money while attending graduate school in biochemistry and conduct several tests on the plant leaves to further assess the condition of the plant:
A) With this information in hand, what questions would you ask the owner?
B) In light of the answers you receive, what other tests would you do?
C) What would you recommend for treatment?
Starch levels Very lowRubisco activity Below normal in vivo levelsMg2+ levels About normalStromal NADPH levels Slightly higher than normal
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ANABOLISM VS. CATABOLISM
Anabolic and catabolic pathways share many of the same reactions, but irreversible reactions are bypassed.
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ANABOLISM VS. CATABOLISM
Anabolic and catabolic pathways undergo coordinate control.
Anabolic and catabolic pathways share many of the same reactions, but irreversible reactions are bypassed.
ATP hydrolysis drives biosynthetic processes even when precursor concentrations are low.
Example of anabolic pathway = gluconeogenesis, the synthesis of glucose from non-carbohydrate precursors, which helps to maintain glucose homeostasis.
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GluconeogenesisRed blood cells
Lactate
One of the two pathways by which the liver maintains blood sugar during times of fasting.
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Glucose Homeostasis
Normally, blood sugar is kept fairly constant by the liver.
Blood sugar rises after food consumption (postprandial period)
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Glucose Homeostasis
First line of defense against a fall in blood sugar is glycogen breakdown.
Glycogen stores are depleted after an overnight fast
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Glucose Homeostasis
Gluconeogenesis becomes significant after about 10 hours of fasting (or during exercise to process lactate).
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Glucose Homeostasis
Hypoglycemia can result from fasting coupled with hard work.
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Central role of oxalo- acetate in gluconeogenesis
Anything that can undergo net conversion to oxaloacetate can result in glucose.
Note that acetyl-CoA does NOT result in glucose.
Lactic acid
~Fig 14-16
Glycerol
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Gluconeo- genesis vs. glycolysis
Fig 14-17
ΔG = -70 kJ/mol
ΔG = -16 kJ/mol
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Bypass #1
Fig 14-17
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Pyruvate carboxylase rxn
Fig 14-18
Acetyl-CoA is a positive effector
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Transport as malate
No transporter for oxaloacetate, so it is converted to malate for transport to cytosol.
Enzyme is malate dehydrogenase.
Reverse reaction in cytosol to regenerate OA, also producing NADH.
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PEP carboxykinase rxn
Fig 14-18
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Bypass II: FBPase-1 rxn
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Bypass III: glucose 6 phosphatase rxn
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Gerty & Carl Cori
Lactate entry
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Lactate entry
Gerty & Carl Cori
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Lactate entry
Lactate entry requires a relatively high NAD+/NADH ratio in the cytosol.
No need to go through malate because reducing equivalents are formed in cytosol by LDH.
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Case Study
Peter agrees to run a half marathon with his friend from the cross country team. He is undertrained for the race, and his legs feel quite tired and heavy when he is done. Afterwards, his friend suggests that they go out for a few beers before heading back to campus. What does Peter tell him?
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(OA)
(OA)
(OA)
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Some animals are highly dependent on gluconeogenesis.
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Some animals are highly dependent on gluconeogenesis.
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Reciprocal Regulation
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Fig 15-22
Regulation of pyruvate carboxylase
Acetyl-CoA acts in a reciprocal manner on pyruvate carboxylase and pyruvate dehydrogenase complex.
High acetyl-CoA stimulates gluconeogenesis, although it is not used directly in the process.
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Fig 15-18
FBPase-1/PFK-1 reciprical control
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Regulation by F26BP
Fig 15-18
F26BP stimulates PFK-1
F26BP inhibits FBPase-1
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Origin of F26BP
Single protein with two domains.
Activity of PFK-2/FBPase-2 is under complex hormonal control
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Fig 15-19Regulation of [F26BP]
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You are a first-year resident called to the post-anesthesia care unit by a nurse who is concerned about a patient she just received from the operating room. The anesthesiologists and surgeons are all busy in the operating rooms due to the recent arrival of multiple trauma patients, so you need to deal with this problem on your own.
The nurse tells you that shortly after arriving in the post-anesthesia care unit, the patient's blood pressure and heart rate began to rise. His temperature is also rising and is currently 40°C. According to the most recent arterial blood gas reading, the patient is acidotic with elevated CO2.
Because you are stumped by these symptoms, the nurse gently informs you that she believes the patient may have malignant hyperthermia, a life-threatening syndrome that occurs during or immediately after general anesthesia.
Along with considering how to treat the condition, you wonder what caused the condition to develop. What is the origin of the patient’s increased body temperature?
Case Study
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Malignant hyperthermia is genetic disorder that causes a rapid increase in body temperature and muscle rigidity when the patient is given general anesthesia.
Symptoms result from a hypercatabolic state because of a mutation in a calcium channel of muscle. The channel opens when bound by certain anesthetics, causing an influx of Ca2+.
Heat results from the following reactions.
Malignant Hyperthermia
PFK-1
FBPase-1
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In-Class Problem
Consider a substrate cycle operating with enzymes X and Y in this pathway:
a) Under intracellular conditions, the activity of enzyme X is 100 pmol/106 cells/s and that of enzyme Y is 90 pmol/106 cells/s. What are the direction and rate of metabolic flux between B and C?
b) Calculate the effect of metabolic flux rate and direction after each of the following:i) Adding an activator that increases the activity of X by
20%ii) Adding an inhibitor that decreases the activity of Y by
20%iii) Adding both the activator and the inhibitor
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Central role of glucose-6-P in metabolism
Gluconeogenesis
Glucose
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Glycogen synthesis overviewGlucose-6-phosphate
UDP-glucose pyrophosphorylase
phosphoglucomutase
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Step 1: phosphoglucomutase
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Step 2: UDP-glucose pyrophosphorylase
Activated glucose donor
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UDP-glucose
Sugar nucleotides are quite common as “activated” monosaccharides primed for further reaction
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UDP-glucoseFig 15-29
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Step 3: Glycogen synthase
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Branching enzyme
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GlycogeninFig 15-33
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GlycogeninFig 15-33
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Regulation via phosphorylation
Phosphorylation inactivates glycogen synthase.
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Regulation via phosphorylation
Dephosphorylation activates glycogen synthase.
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Regulation via phosphorylation
Insulin inactivates glycogen synthase kinase, activating glycogen synthase.
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Role of insulinFig 15-39
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Regulation via phosphorylation
Insulin activates protein phosphatase 1 (PP1), turning on glycogen synthase.
Glucagon and epinephrine inactivate protein phosphatase 1 (PP1), turning off glycogen synthase.
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Hormone effects
Fig 15-41
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