Glucose

Bypass 2 -What enzymes used and what enzyme are we bypassing? -Where does this occur?

- Bypassing Phosphofructokinase - Enzyme used is Fructose 1,6-biphosphotase (Cytosol)

4 sources of building blocks for gluconeogenesis

1) Lactate --> Pyruvate/alanine (Cori cycle). 2) Amino Acids (except leucine and lysine) 3) Glycerol (fats - tryglycerides cannot be used in animals, but the glycerol from lipids can) 4) CAC intermediates (conversaion to citrate/oxalacetate/malate).

State the 3 bypasses in glyconeogensis

1) Pyruvate Kinase (PK) 2) Phosphofructokinase 3) Hexo/glucokinase

Inputs if you simply reversed glycolysis? (If the enzymes were all reversible). What is deltaG?

4ATP, 2GTP, 2NADH DeltaG is positive

Glycogen v Glucose water attracted

Glucose attracts water, glycogen doesn't attract AS MUCH water.

Why do we need to make glucose?

Glycogen stores and blood glucose not enough for daily activities

Where is glycogen stored?

In the cytosol of many tissues, eg. liver, muscle, kidney.

Do glycogen synthesis and degradation occur at the same time?

NOOO

Bypass 1 -What enzymes used and what enzyme are we bypassing? -Where does this occur?

- Bypassing Pyruvate Kinase to get from Pyruvate to Oxaloacetate. - Enzymes used are Pyruvate Carboxylase (Mitochondria) and PepCK (Cytosol) - 2 ATP used

Bypass 3 -What enzymes used and what enzyme are we bypassing? -Where does this occur?

- Bypassing hexo/glucokinase - Enzyme used is GLucose 6-phosphotase (ER)

McArdle's disease Results

- Excess glycogen which occurs in musclces. - Glycogen in muscles, but lack of glucose release, little glycogen phosphorylase activity in muscle. -Results: Muscle cannot use & utilize glycogen storage. Glycogen granules abnormally large & inhibit muscular contraction, severe cramps. (Note: Glycogen can still be relased from liver, but takes a while to get to muscles and other tissues)

Describe structure of glycogen, and 2 bonds

- Is similar to starch, but can pack more densely (space efficency). - Protein is middle is glycogenin = has two binding ends that allow the glucose molecules to attach to it. 2 bonds: 1) Alpha 1,4-glycosidic bonds 2) alpha 1,6 glycosidic bond

Von Gierke's disease Cause Results Treatment

- Type 1 GSD (untreated type 1 diabetes, and alcoholics) - Mutation of Glucose 6-phosphatase, so can't release glucose from liver into blood. -Results: Hypoglycaemia (very low blooc glucose), excess G6P in cells, elevated lactate during fasting, Gout (G6P converted to uric acid which accumulates in joints), enlarged liver and kidney. -Treatment Fructose (has its own transporters) and other carbohydrates.

Describe process of Glucogenesis

1) Glucose enter throuh cell membrane through glucose transporter. 2) Hexokinase/Glucokinase (liver and kidney only) phosphorlyate the glucose (ATP-->ADP) -->Glucose 6-phosphate so glucose can't go back through the transporter. 3) Glucose 6-phosphate is converted to Glucose 1-phosphate 4) Glucose 1-phosphate + UTP -->UDPG 5) UDPG is added to glycogenin by Glycogen synthase

Name the 3(-4) enzymes involved in glycogenolysis

1) Glycogen Pohsphorylase 2) Glycogen de-branching enzyme (actually 2 enzymes) 3) Phosphoglucomutase (Found in muscles and liver)

Describe the process of Glycogenolysis

1) Glycogen phosphorlyase adds a phosphate at the 1 position, and moves the 1st molecule away. (This only works to 5 glycosyl residues away (leaving 4). 2) Debranching enzyme acts as a transferase to transfer 3 glycosyl units and the a-1,6 link. The remaining glucose is lost from the cell, or an ATP must be used (hexokinase) to trap it. 3) Phosphoglucmutase catalyzes G1P-->G6P (shifts phosphate to 6th carbon). G6P can then be used for diff things in cell (g. metabolism or growth).

3 reasons why glycogenolysis is PHOSPHORYLIS, not hydrolysis?

1) Hydrolysis will leave an unphosphorylated glucose 2) Ensures released glucose is charged and trapped in cell (important in muscles) 3) Saves an ATP each time. (Pi is used directly)

What is glycogen phosphorlyase inhibted by

ATP, glucose and G6P, as don't need to breakdown glycogen if these are in good supply.

What is glycogen metabolism stimulated/inhibited by? why is this necessary?

By glucagon, or adrenalin. Stimulation will cause a cascade of enzymes, making phosphorlyase active. Adrenalin makes glycogen synthase INACTIVE. This ensures glygocen is not being made as it is being broken down - Futile cycle.

What does G6pase do Where is G6pase found? Why?

Cleaves phosphate off G6P-->glucose, goes into blood. Found in liver or kidney for use elsewhere, as muscle cannot export glucose (glucogenesis)

Why must gluconeogensis and glycolysis not occur at the same time in terms of ATP

Gluconeogensis consumes ~12ATP, and glycolysis makes 2ATP. Thus mismatch of ~10ATP, so 2 pathways must not run at same time otherwise ATP loss.

Glycogenolysis

Glucose release mediated by light or hormones (eg. adrenalin) or hunger (glucagon).

what does insulin drive

Glucose storage and growth.

Glucogenesis

Glucose synthesis

What is glycogen storage driven by

Insulin

Why is glucose stored as glycogen and not glucose?

It must be made into its polymer for storage as in glucose form, it will attract water causing the cell to swell and burst. Glycogen however is water insoluble, and efficently accessed. Glycogen doesn't attract as much water.

Liver v Muscle amount of glycogen storage

Liver up to 10%, muscles 1-2%. This is due to space limits in cardiac muscles.

Glycogen storage that can be accessed for other tissues?

Storage in the liver and kidney. (Muscle cell glycogen cannot be used for other cells).

Of what end of glucose does glycogen breakdown occur

The Non-reducing end

Gluconeogenesis

The reverse of glycolysis (with some exceptions) - to make glucose. - Pyruvate -->Glucose - Most of enzymes are at equilibrium, so are reversible. - However some enzymes are irreversible, and process takes ALOT of energy.

Name 2 types of glycogen storage disease

Von Gierke's disease Mc Ardle's disease

of which end if glucose added and taken away from the glycogen polymer

the Non-reducing end. (reducing end is bound to the glycogenin)

How many inputs required for glyconeogensis? What is deltaG

~12 DeltaG is negative