Gluconeogenesis and Carb Storage Flashcards by Rawan Alkhateeb

Gluconeogenesis require how much more energy than glycolysis requires?

4 ATP
2 NADH
2 GTP

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What kind of cells in the body rely on glycolysis?

RBC
Brain and CNS
Muscle

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Location of Glycolysis

Cytosol only

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Gluconeogenesis location

the Liver and Kidney mitochondria, cytosol, ER lumen

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First step of Gluconeogenesis and it’s location

G-6-P is converted into Glucose via Glucose 6- phosphatase ( this enzyme is ONLY found in the liver)
location of this step : luminal side of ER

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Lack of insulin disease

type 1 diabetes

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insufficient insulin/ insulin resistance

type 2 diabetes

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Type 1 and 2 causes gluconeogenesis pathway to be? and this causes

uninhibited, the liver pumps out glucose contributing to the already high blood glucose

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the liver pumps out glucose into?

blood stream

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A drug used to treat type 2 diabetes?

Metformin

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How does metformin work?

stimulates AMPK

which results in insulin INDEPENDENT inhibition of gluconeogenesis

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Insulin levels in relation to states of 
Fed
Fasted
Stress
Effect on break down of glycogen

Fed : Increase levels of insulin
Fasted : Low levels of insulin
Stress : no effect
Insulin would INHIBIT breakdown of glycogen

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Glucagon levels in relation to states of 
Fed
Fasted
Stress
Effect on break down of glycogen

Fed : low
Fasted : high
Stress : no effect
Glucagon would promote breakdown of glycogen

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Corticosteroids levels in relation to states of
Fed
Fasted
Stress
Effect on break down of glycogen

Fed: no effect
Fasted: Increase levels
stress : Increase levels
Promote glycogen break down

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Adrenaline levels in relation to states of
Fed
Fasted
Stress
Effect on break down of glycogen

Fed: No effect
Fasted: No effect
Stress : Increase
Effect of hormone: promote glycogen breakdown

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Liver contains glucose 6-phosphatase.
Muscle does not have this enzyme.
WHY?

The liver releases glucose to the blood to be taken up by brain and active muscle. The liver regulates blood glucose levels (gluconeogenesis).
The muscle retains glucose 6-phosphate to be use for energy (glycolysis). Phosphorylated glucose is not transported out of muscle cells (no gluconeogenesis).

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Gluconeogenesis is needed to maintain blood glucose levels under ____ conditions.

fasting conditions.

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Precursors of gluconeogenesis are

lactate, glycerol, and several amino acids, but never acetyl-CoA.

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Gluconeogenesis requires

ATP, GTP, and NADH.

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This ORGAN is the primary gluconeogenic tissue; the pathway requires participation of enzymes located in the ?

organ: Liver

mitochondria, cytosol, and endoplasmic reticulum of the liver.

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The unique reactions of gluconeogenesis are catalyzed by :

pyruvate carboxylase, phosphoenolpyruvate carboxykinase (PEPCK), fructose 1,6-bisphosphatase, and glucose 6-phosphatase.

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The rate-limiting reaction in gluconeogenesis is catalyzed by fructose 1,6-bisphoshatase which is ______ by fructose 2,6-bisphosphate (F2,6BP) and stimulated by glucagon. Note, reciprocally, F2,6BP ______phosphofructokinase in glycolysis.

The rate-limiting reaction in gluconeogenesis is catalyzed by fructose 1,6-bisphoshatase which is inhibited by fructose 2,6-bisphosphate (F2,6BP) and stimulated by glucagon. Note, reciprocally, F2,6BP stimulates phosphofructokinase in glycolysis.

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_____ is the most common disease related to gluconeogenesis dysfunction, due to the importance of gluconeogenesis in maintaining blood glucose homeostasis

Diabetes is the most common disease related to gluconeogenesis dysfunction, due to the importance of gluconeogenesis in maintaining blood glucose homeostasis

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Hence the average person with type-2 diabetes has a __times higher rate of gluconeogenesis. The drug ____ can treat type-2 diabetes by inhibiting gluconeogenesis.

Three times, Metformin

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Type 1 Diabetes

lack of insulin; results from the body’s failure to produce enough insulin. Also known as insulin

Type 2 Diabetes

insulin resistance; cells fail to respond properly to insulin. Increased rate of gluconeogenesis results in increased blood glucose levels.

The synthesis and breakdown of glycogen is regulated to maintain blood glucose levels. Which organ is this important for?

LIVER

In ___ - The synthesis and breakdown of glycogen is regulated to meet the energy requirements of the muscle cell.

muscle

Glycogen builds during what time of day?

After dinner in preperation for the night while fasting

Glycogen is stored in ?

Glycogen Granulues of Muscle Adipose Liver

Branched structure

1,6 glycosidic linkage

adds length

1,4 glycosidic linkage

RLS of gluconeogenesis | Fructose 1, 6 Biphosphate to Fructose 6 phosphate takes place in?

ER lumen

Pyruvate to Oxaloacetate to PEP

Pyruvate carboxylase to oxaloacetate to malate... this happens in mitochondria. Malate is able to out of mitochondria. Malate is turned into OAA to PEP via PEP carboxykinase .

glycogen synthase adds what type of linkage? what is needed?

1,4 linkage for length and needs glucose 1-P + UDP to turn into UDP glucose. UDP glucose is used along with glycogen synthase

branching enzyme adds what type of linkage?

1,6 linkage

glycogenin molecule has what?

Tyr-OH group

What does glycogenin do

it self flycosolates and takes UDP glucose and releases the UDP and primes the glucose and adds it to glycognenin to make a primed glycogenin

primed glycogenin is ready for?

glycogen synthesis, via glycogen sythetase and branching enzyme

glycogen molecule: A core protein of glycogenin is surrounded by branches of glucose units.

glycogenin is surrounded by branches of glucose units.

glycogen degradation | glycogen to glucose 1 phosphate via?

glycogen phosphorylase

g6p can go to..

glycolysis, make glucose, ppp--> ribose nadph

what enzyme removes 1,4 likage?

phosphorylase

what enzyme removes 1,6 linkages?

alpha 1, 6 glucosidase

When blood glucose levels are high, insulin

stimulates glycogen synthesis.

? regulates blood glucose levels.

Glycogen metabolism in liver

Phosphorylase a normally binds PP1 (protein phosphatase 1), keeping PP1 inactive. ___causes the dissociation of PP1 from phosphorylase a, which activates __

glucose, PP1

This dissociated active PP1 then ___glycogen synthase 1, thereby ____.

dephosphorylates, activating it

At the same time, the inhibition of phosphorylase a by glucose results in a reduced of phosphorylase a on PP1 that now has increased activity to

inhibition,activate glycogen synthase.

___ Stimulates Glycogen Synthesis in Muscle

Insulin

is responsive to epinephrine.

Muscle

is responsive to glucagon and

Liver

Can epi and glucagon stimulate glycogen breakdown?

TRUE

activate adenylyl cyclase, leading to a rise in cAMP. cAMP stimulates glycogenolysis to glucose, leading to increased blood glucose levels.

Glucagon and beta-agonists

beta-agonists do. Glycogenolysis is simulated by?, but since muscle does not synthesize glucose, it converts pyruvate to lactate which is secreted into the bloodstream.

beta-agonists do.

The highly branched structure of glycogen

provides a large number of sites for addition or removal of glucose to facilitate a more rapid response to bodily needs. Its proteinaceous core (glycogenin) is a self-glucosylating enzyme that provides the poly-glucose primer for glycogen synthesis.

the rate-limiting steps of glycogen synthesis and degradation, respectively.

Glycogen synthase and glycogen phosphorylase catalyzes

provides the glucose residues for the synthesis of glycogen.

sugar nucleotide, UDP-glucose

promote degradation of glycogen through a cAMP-mediated cascade of phosphorylation steps. Receptors for glucagon are found only on liver cells, while epinephrine receptors (adrenergic receptors) are found in both muscle and liver cells.

Epinephrine and glucagon

Degradation of glycogen in the liver can supply blood glucose because liver contains ? (gluconeogenesis). Muscle does not contain this enzyme. In muscle, breakdown of glycogen is used to generate energy (ATP) through glycolysis.

glucose 6-phosphatase

Glucose stimulates ___of Glycogen synthase by PP1 to form

de-phosphorylation , active Glycogen synthase enzyme

Glucose-6-phosphatase deficiency. Final step of gluconeogenesis and glycogenolyis to produce glucose is defected. Growth failure and lactic acidosis; no pathologic muscle symptoms. less glucose at night

von gierekes

Glycogen debranching enzyme deficiency. Defect in glycogenolyis Myopathies. run out of energy

coris disease

Glycogen branching enzyme deficiency. Defect in glycogen synthesis. Failure to thrive; death at about age 5 years. No pathologic muscle symptoms.

(Anderson disease).

Glycogen phosphorylase deficiency. Defect in glycogenolyis. Exercise-induced muscle cramps; rhabdomyolysis (breakdown of damaged skeletal muscle

(McArdle disease).