carbohydrate catabolism i chapter 14 and parts of 15 march 5, 2015 bc368 biochemistry of the cell ii
TRANSCRIPT
Carbohydrate Catabolism IChapter 14 and parts of 15
March 5, 2015
BC368Biochemistry of the Cell II
BC368Biochemistry of the Cell II
Catabolism
Central Role of Glucose
Overview of glycolysis
Two phases of glycolysis
Two phases of glycolysis
Preparatory Phase
Fig 14-2
pg 526
Reaction 1: phosphorylation
Reaction 1: phosphorylation
Fig 14-3
Tissue-specific isozymes.
Hexokinase vs. glucokinase
Fig 15-14
Reaction 2: isomerization
aldose ketose
Reaction 2: isomerization
Fig 14-3
Reaction 3: phosphorylation
Reaction 3: phosphorylation
Fig 14-3
Reaction 4: cleavage
Reaction 4: cleavage
Fig 14-3
Reaction 5: isomerization
Reaction 5: isomerization
Fig 14-3
Keeping Track of CarbonsKeeping Track of Carbons
glucose
G3P
Fig 14-2
Reaction 6: oxidation
Reaction 6: oxidation
Fig 14-3
Reaction 7: substrate level phosphorylation
Reaction 8: shift of phosphoryl group
Reaction 8: shift of phosphoryl group
Fig 14-3
~Fig 14-8Fig 14-9
Reaction 9: dehydration
Reaction 10: substrate level phosphorylation
https://www.youtube.com/watch?v=EfGlznwfu9U
Energy investment
Cleavage
Energy Harvest
Summary
Efficiency
FeederPathways
Fig 14-9
glycerol
Glycerol 3-P
All carbohydrates enter glycolysis
In muscle, often via hexokinase
Case Study
A 9-month-old is brought to your clinic with recurrent bouts of sweating and vomiting. Symptoms began shortly after weaning and introduction to solid foods. Testing reveals hypoglycemia and lactic acidosis after consumption of milk formula or fruit. Enzyme activity testing reveals a deficiency in fructose 1-phosphate aldolase.
Notably, her 3-year-old brother has a marked aversion to fruit.
Fructose intolerance
Hereditary fructose intolerance results from a defect in fructose breakdown in the liver, usually in aldolase.
GlycogenBreakdown
GlycogenPhosphorylase
Glycogen phoshorylase catalyzes the simultaneous phosphorylation and cleavage of an -1,4 linked glucose from a non-reducing end of glycogen.
This reaction is called “phosphorolysis.”
GlycogenBreakdown
Fig 15-12
Pyridoxal phosphate
GlycogenBreakdow
nStep 1.
Glycogen Phosphorylas
e
Fig 14-12
Fig 15-12GlycogenBreakdow
n
Phospho- glucomutase
Fig 15-29
G6P fate depends on tissue.
In muscle, G6P proceeds through glycolysis.
In liver, G6P is converted to glucose.
Limit Dextrins
GlycogenBreakdow
n
Debranching enzyme
Fig 15-28
Glycogen storage diseases
Fig 14-3
Fate of the products, pyruvate and NADH
Fig 14-3
Fermentation in Animals
• Lactic acid from skeletal muscle is sent into the bloodstream.
• Lactate threshold occurs when production exceeds clearance. Glycolysis cannot continue.
Fermentation in Animals
Cori Cycle
Fermentation in Yeast
Fermentation in Yeast
Pyruvate decarboxylase reaction
Alcohol dehydrogenase reaction
Irreversible steps are regulated:
Hexokinase/Glucokinase
Phosphofructokinase I
Pyruvate Kinase
Regulation of glycolysis
Tissue-specific isozymes.
Glucose + ATP G6P + ADP
Feedback inhibition by G6P.
Control of Hexokinase
Control of PFK-1
Many allosteric effectors; e.g., ATP.
H+,
ATP is an allosteric inhibitor of PFK-1.
Two binding sites: substrate and allosteric site.
Control of PFK-1
Control of pyruvate kinase
PEP + ADP pyruvate + ATP
Fig 15-19
Control of pyruvate kinase
Control of glycogen phosphorylase
phosphorylase b (inactive)
phosphorylase a (active)
phosphorylation
glycogen breakdown
Glycogen phosphorylase is activated upon phosphorylation by phosphorylase kinase.
Phosphorylase kinase is activated upon phosphorylation by protein kinase A (PKA).
Glycogen phosphorylase is activated upon phosphorylation by phosphorylase kinase.
PKA is activated by cyclic AMP, which is produced by a G-protein in response to epinephrine/glucagon.
Phosphorylase kinase is activated upon phosphorylation by protein kinase A (PKA).
Glycogen phosphorylase is activated upon phosphorylation by phosphorylase kinase.
Fig 14-1
Transketolase requires thiamine pyrophospate (TPP) as a coenzyme
NADPH is necessary to protect against reactive oxygen species
Ribose 5-P is necessary in rapidly dividing cells
•Rxns 1 and 3 produce NADPH
•Rxn 4 produces ribose-5- phosphate
Glucose 6-P + 2 NADP+ + H2O Ribose 5-P + 2 NADPH + 2 H+ + CO2
Oxidative phase
From C1
Key Enzyme: G6P Dehydrogenase
Case StudyOmar’s mother noticed that every time she served falafel, her son complained of feeling tired, hot, headachy, and sick to his stomach. At first she thought he was just being fussy, but sometimes he would actually look yellow. Medical testing confirmed hemolytic anemia. What’s up with Omar?
A deficiency in G6PDH is the most common human enzyme defect, affecting more than 400 million people worldwide. Protective against malaria.
Divicine leads to reactive oxygen species
Favism!
Case StudyOmar’s mother noticed that every time she served falafel, her son complained of feeling tired, hot, headachy, and sick to his stomach. At first she thought he was just being fussy, but sometimes he would actually look yellow. Medical testing confirmed hemolytic anemia. What’s up with Omar?
X
Regulation
G6P dehydrogenase is allosterically inhibited by NADPH; activated by NADP+
Glucose 6-P + 2 NADP+ + H2O Ribose 5-P + 2 NADPH + 2 H+ + CO2
Oxidative Phase
Some cells need NADPH but not ribose 5-P
Ribose 5-P can be recycled in the nonoxidative phase
Fig 14-22
Fig 14-23
Pentose Phosphate Pathway: Nonoxidative
Phase
Carbon Shuffling Reactions
Glucose6-phosphate
Ribose5-phosphate
Fig 14-23