BC368

Biochemistry of the Cell II

Carbohydrate Catabolism I
Chapter 14 and parts of 15
March 5, 2015
Catabolism
Central Role of Glucose
Overview of glycolysis
Two phases of glycolysis
Two phases of glycolysis
Preparatory Phase

Fig 14-2
 Reaction 1: phosphorylation

pg 526
Reaction 1: phosphorylation

Fig 14-3
 Hexokinase vs. glucokinase

Tissue-specific
isozymes.

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 Carbons

G3P

glucose
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 14-9
~Fig 14-8
Reaction 9: dehydration
Reaction 10: substrate level phosphorylation
 Summary

Energy
investment

Cleavage

Energy
Harvest

https://www.youtube.com/watch?v=EfGlznwfu9U
Efficiency
 Feeder
Pathways

 All
carbohydrate
s enter
glycolysis

 In muscle,
glycerol often via
hexokinase
Glycerol 3-P

Fig 14-9
 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.
Glycogen
Breakdown
 Glycogen
Breakdown
 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.”

Glycogen
Phosphorylase
 Glycogen
Breakdown
Fig 15-12
Step 1.
Glycogen
Phosphorylase

Pyridoxal phosphate

Fig 14-12
 Glycogen
Breakdown
Fig 15-12

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
 Glycogen
Breakdown
Debranching
enzyme

Fig 15-28
Glycogen storage diseases
Fate of the products, pyruvate and NADH

Fig 14-
Fig 14- 3

3
Fermentation in Animals
 Fermentation in Animals
• Lactic acid from skeletal muscle is sent into the
bloodstream.
• Lactate threshold occurs when production exceeds
clearance. Glycolysis cannot continue.
Cori Cycle
Fermentation in Yeast
Fermentation in Yeast
Pyruvate decarboxylase reaction
Alcohol dehydrogenase reaction
Regulation of
glycolysis

Irreversible steps are

regulated:
Hexokinase/Glucokinase

Phosphofructokinase I

Pyruvate Kinase
 Control of Hexokinase

Glucose + ATP  G6P + ADP

Feedback inhibition by
G6P.

Tissue-specific
isozymes.
 Control of PFK-1

Many allosteric effectors; e.g., ATP.

H+,
 Control of PFK-1

ATP is an
allosteric
inhibitor of PFK-
1.

Two binding
sites: substrate
and allosteric
site.
 Control of pyruvate kinase

PEP + ADP  pyruvate + ATP

Control of pyruvate kinase

Fig 15-19
 Control of glycogen
phosphorylase

phosphorylation

phosphorylase b phosphorylase a
(inactive) (active)

glycogen
breakdown
Glycogen phosphorylase
is activated upon
phosphorylation by
phosphorylase kinase.
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.

Phosphorylase kinase is
activated upon
phosphorylation by protein
kinase A (PKA).

PKA is activated by
cyclic AMP, which is
produced by a G-protein in
response to
epinephrine/glucagon.
Fig 14-1
 NADPH is
necessary to
protect against
reactive oxygen
species

Transketolase
requires
thiamine
pyrophospate
(TPP) as a
coenzyme

Ribose 5-P is
necessary in rapidly
dividing cells
 Oxidative phase

•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

From C1
Key Enzyme: G6P
Dehydrogenase
 Case Study
Omar’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?

Divicine leads to reactive

Favism!
oxygen species

A deficiency in G6PDH is the most common human enzyme

defect, affecting more than 400 million people worldwide.
Protective against malaria.
 Case Study
Omar’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+
 Oxidative Phase

Glucose 6-P + 2 NADP+ + H2O 

Ribose 5-P + 2 NADPH + 2 H+ + CO2

Some cells need NADPH but

not ribose 5-P

Ribose 5-P can be recycled

in the nonoxidative phase
 Pentose Phosphate Pathway:
Nonoxidative Phase

Fig 14-22

Fig 14-23
 Ribose
5-phosphate Carbon Shuffling Reactions

Glucose
6-phosphate

Fig 14-23