Glycolysis & Glycogen* Flashcards

1
Q

Describe the types of reactions catalyzed and the strategies employed during the 10-step glycolytic pathway that converts one glucose to two pyruvate

A

Hexokinase phosphorylates Glu to give G6P. Glucokinase in liver has less affinity. G6P is trapped in the cell since it has no transporter. Glycolysis occurs in the cytosol of the cell. 1 ATP used.

G6P -> F6P. Enzyme: Phosphoglucoisomerase.

F6P + 1 ATP -> F1,6BF. Enzyme: Phosphofructokinase. This is a key **regulation step.

Aldolase cleaves F1,6BF into DHAP + G3P (glyceraldehyde 3 phosphate). Next, DHAP will be converted to G3P by triose isomerase.

Up to this point, we invested 2 ATP.

G3P -> 1,3BPG by G3P dehydrogenase.

1,3 Biphosphoglycerate -> 3 phosphoglycerate + 2 ATP by phosphoglycerate kinase. We’re now even for the ATP used by Hexokinase and Phosphofructokinase. This is an example of Substrate-level Phosphorylation

3 phosphoglycerate -> 2 phosphoglycerate by phosphoglycerate mutase

2 phosphoglycerate -> phosphoenolpyruvate by enolase

phosphoenolpyruvate -> pyruvate + 1 ATP by pyruvate kinase. The PK reaction is another example of Substrate-level Phosphorylation

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2
Q

Discuss the mechanism of the enzymes in the glycolytic pathway with regard to the amino acid residues, coenzymes, and cofactors that participate in their reactions

A

Hexokinase/ glucokinase = ATP

Phosphofructokinase = ATP

Glyceraldegyde 3 phosphate dehydrogenase = NAD+ & Acyl thioester

Phosphoglycerate kinase = ADP

phosphoglycerate mutase = phosphohistidyl intermediate

Pyruvate kinase = ADP

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3
Q

Identify the steps that involve the use and production of ATP, and quantitate the net gain in ATP achieved by the glycolytic pathway

A

Invest 1 ATP:

hexokinase

Phosphofructokinase

Generation of ATP:

2 ATP phosphoglycerate kinase

2 ATP purvate kinase

Net gain of two ATP and two NADH in converting Glu to two Pyr.

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4
Q

Describe the fate of glycolytic NADH under both aerobic and anaerobic conditions

A

Under aerobic conditions, glycolytic NADH (2 of them) is indirectly oxidized by oxidative phosphorylation and pyruvate enters the TCA cycle

Under anaerobic conditions, pyruvate is reduced by glycolytic NADH via lactate dehydrogenase to give lactate

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5
Q

Describe how fructose, mannose and galactose enter the glycolytic pathway

A

Galactose becomes G6P

Mannose & muscle Fructose become F6P

Hexokinase (but not liver glucokinase) converts Fructose to F6P

Galactose involves Galactokinase, a UMP Transferase, an Epimerase, and Phosphoglucomutase

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6
Q

Describe the types of reactions catalyzed during the synthesis and breakdown of glycogen

A

Glycogen synthesis:

G6P -> G1P by phosphoglucomutase

G1P -> UDP-Glucose by UDP glucose phosphorylase

UDP-Glucose -> Glycogen by Glycogen synthase & Branching enzyme. Glycogen is a branched polymer.

Glycogen breakdown:

Glycogen -> G1P by Debranching enzyme & glycogen phosphorylase

G1P -> G6P by phosphoglucomutase

Glycolysis

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7
Q

Recognize the special role played by liver glycogen in maintaining blood glucose

A

Liver glycogen can release glucose into the blood or store glucose in the liver depending on the body’s needs.

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8
Q

Calculate the cost of temporarily storing a glucose-6-P molecule as a unit in a glycogen polymer when you begin with glucose-6-P and end with glucose-6-P to be used as a substrate for glycolysis.

A

The cost if you’re going to use the released G6P for glycolysis is 1 UTP → UDP + Pi per G6P temporarily stored, plus 0.1 ATP/Glu to rephosphorylate the 10% of the Glu units released by hydrolysis of the α(1-6)glycosidic bond at branch points, for a total of 1.1 ATP/G6P stored

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9
Q

Calculate the cost of temporarily storing a glucose molecule as a unit in a glycogen polymer when you begin with glucose just taken up from the blood stream and you end with glucose about to be released back into the blood stream.

A

The cost in liver cells when blood Glu is taken up, stored, and then released back into the blood stream is 1 ATP used by Glucokinase, plus 1 UTP used by the UMP transferase, or an equivalent of 2 ATP per blood Glu temporarily stored in the liver

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10
Q

Type I Von Gierke disease

A

Defective: Glucose-6-phosphatase or transport system

Organs affected: Liver and kidney

Glycogen in the organs: increases

Clinical features: Massive enlargement of the
liver. Failure to thrive. Severe hypoglycemia, ketosis, hyperuricemia, hyperlipemia.

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11
Q

Type IV Anderson disease

A

Defective: Branching enzyme (α-1,4 → α-1,6)

Organs affected: Liver and spleen

Glycogen in the organs: Normal amount; very long outer branches.

Clinical features: Progressive cirrhosis of the liver. Liver failure causes death, usually before age 2.

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12
Q

Type V McArdle disease

A

Defective: Phosphorylase

Organ affected: Muscle

Glycogen in the organ: Moderately increased amount, normal structure.

Clinical features: Limited ability to perform strenuous exercise because of painful muscle cramps. Otherwise patient is normal and well developed. People usually find out when they do high school sports.

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