7 glycogen metabolism-_gluconeogenesis

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23.7 Glycogen Metabolism

23.8 Gluconeogenesis: Glucose Synthesis

Metabolic Pathways for Carbohydrates

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Glycogenesis

Glycogenesis:

Stores glucose by converting glucose to

glycogen.

Operates when high levels of glucose-6-

phosphate are formed in the first reaction of

glycolysis.

Does not operate when energy stores

(glycogen) are full, which means that

additional glucose is converted to body fat.

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Diagram of Glycogenesis

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Formation of Glucose-6-Phosphate

Glucose is converted to glucose-6-phosphate

using ATP.

Glucose-6-phosphate

O

OH

OH

OH

OH

CH2OP

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Formation of Glucose-1-Phosphate

Glucose-6-phosphate is converted

to glucose-1-phosphate.

Glucose-6-phosphate Glucose-1-phosphate

O

O

OH

OH

OH

CH2OH

P

O

OH

OH

OH

OH

CH2OP

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UDP-Glucose

UTP activates glucose-1-phosphate to form UDP-glucose and pyrophosphate (PPi).

UDP-glucose

O

O

OH

OH

OH

CH2OH

P

O

O-

O P

O

O-

O CH2O

OHOH

N

N

O

H

O

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Glycogenesis: Glycogen

The glucose in UDP-glucose adds to glycogen.

UDP-Glucose + glycogen glycogen-glucose + UDP

The UDP reacts with ATP to regenerate UTP.

UDP + ATP UTP + ADP

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Glycogenolysis

Glycogenolysis

is the break

down of

glycogen to

glucose.

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Glycogenolysis

Glycogenolysis:

Is activated by glucagon (low blood glucose).

Bonds glucose to phosphate to form glucose-1-

phosphate. Glycogen-glucose + Pi Glycogen + glucose-1-phosphate

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Isomerization of Glucose-1-

phosphate

The glucose-1-phosphate isomerizes to glucose-

6-phosphate, which enters glycolysis for energy

production.

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Glucose-6-phosphate

Glucose-6-phosphate:

Is not utilized by brain and skeletal muscle

because they lack glucose-6-phosphatase.

Hydrolyzes to glucose in the liver and kidney,

where glucose-6-phosphatase is available providing

free glucose for the brain and skeletal muscle.

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Utilization of Glucose

Glucose:

Is the primary

energy source for the

brain, skeletal

muscle, and red

blood cells.

Deficiency can

impair the brain and

nervous system.

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Gluconeogenesis: Glucose

Synthesis

Gluconeogenesis is:

The synthesis of

glucose from

carbon atoms of

noncarbohydrate

compounds.

Required when

glycogen stores are

depleted.

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Gluconeogenesis: Glucose

Synthesis

Carbon atoms for gluconeogenesis from lactate,

some amino acids, and glycerol are converted to

pyruvate or other intermediates.

Seven reactions are the reverse of glycolysis and

use the same enzymes.

Three reactions are not reversible.

Reaction 1 Hexokinase

Reaction 3 Phosphofructokinase

Reaction 10 Pyruvate kinase

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Gluconeogenesis: Pyruvate to

Phosphoenolpyruvate

Pyruvate adds a carbon to form oxaloacetate by

two reactions that replace the reverse of reaction

10 of glycolysis.

Then a carbon is removed and a phosphate added

to form phosphoenolpyruvate.

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Phosphoenolpyruvate to Fructose-

1,6-bisphosphate

Phosphoenolpyruvate is converted to fructose-

1,6-bisphosphate using the same enzymes in

glycolysis.

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Glucose Formation

A loss of a phosphate from fructose-1,6-

bisphosphate forms fructose-6-phosphate and Pi.

A reversible reaction converts fructose-6-

phosphate to glucose-6-phosphate.

The removal of phosphate from glucose-6-

phosphate forms glucose.

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Cori Cycle

When anaerobic conditions occur in active

muscle, glycolysis produces lactate.

The lactate moves through the blood stream to the

liver, where it is oxidized back to pyruvate.

Gluconeogenesis converts pyruvate to glucose,

which is carried back to the muscles.

The Cori cycle is the flow of lactate and glucose

between the muscles and the liver.

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Pathways for Glucose

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Regulation of Glycolysis and

Gluconeogenesis

High glucose levels and insulin promote glycolysis.

Low glucose levels and glucagon promote

gluconeogenesis.

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Ethanol

Ethanol is not a carbohydrate, nor is it a precursor for the biosynthesis of carbohydrates.

However, ethanol can replace sizable amounts of carbohydrates as an energy source when large amounts are ingested.

It is present in the blood of most humans, being produced by intestinal flora.

People ingest ethanol in variable amounts in beverages and fermented fruits.

Ethanol is metabolized in the liver to acetate and adds to the caloric content of the diet.

Ethanol has an energy equivalent of 7 kcal/g.

100 mL of table wine has ethanol corresponding to about 72 kcal.

A “jigger” of whiskey furnishes approximately 120 kcal.

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Ethanol continue: When ethanol is metabolized in the liver, alcohol dehydrogenase oxidizes it first to

acetaldehyde.

CH3CH2OH + NAD+ → CH3CHO + NADH + H+

The acetaldehyde is oxidized further to acetate.

CH3CHO + NAD+ + H2O → CH3COO- + NADH + H+

A small fraction of the alcohol may be oxidized by other systems: Cytochrome P450 oxidase (also involved in detoxification of many drugs);

Catalase

The acetate produced from ethanol largely escapes from the liver and is converted to acetyl CoA and then to carbon dioxide by the way of the Krebs cycle.

The acetyl that stays in the liver may act as a precursor for lipid biosynthesis.

A significant consequence of metabolism of ethanol in the liver is the twofold to threefold increase in the NADH/NAD+ ratio.

With higher concentrations of blood alcohol, the concentration of NADH remains high, and the availability of NAD+ drops and limits both the further oxidation of ethanol and the normal functioning of other metabolic pathways, such as gluconeogenesis.

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“Fatty liver”

Chronic consumption of significant amounts of alcohol may lead to a “fatty liver”, in which the excess of triacylglyceride is deposited.

This is caused by several contributing factors: Reduced triacylglyceride secretion from the liver

Reduced rates of fatty acid oxidation

Increased rates of lipid biosynthesis

These processes are associated with the increased acetyl CoA and NADH/NAD+ ratio in the liver that results from ethanol oxidation.