Carbohydrate Catabolism I Chapter 14 and parts of 15 March 5, 2015 BC368 Biochemistry of the Cell II.

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