Energy Storage Flashcards

1
Q

Glucose is the preferred fuel

A

Some tissues have an absolute requirement for glucose as an energy source
Red blood cells - dont have a M
Neutrophils - main objective is elimination of ROS, dont have time for glycolysis
Innermost cells of kidney medulla - OxP is limited so rely on glucose
Lens of the eye - “

If plasma glucose falls, hypoglycaemia ensues e.g. diabetic patients

Stable blood glucose level absolutely essential for normal brain function.

Past 0.6 moles/L GLUT1 cant transport glucose into the brain - therefor brain damage may follow

To enable blood glucose to be kept at required levels, a store of glucose is required…GLYCOGEN

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2
Q

Glycogen is stored as granules

A

Muscle glycogen - Distinction between intra- (Intra) and intermyofibrillar (Inter) glycogen.

Glycogen storage granules in hepatocyte.

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3
Q

Glycogen structure

A

Glycogen is a polymer consisting of chains of glucose residues

Chains are organized like the branches of a tree originating from a dimer of the protein glycogenin
(acts as a primer at core of glycogen structure).

Glucose residues linked by

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4
Q

Glycogenesis

A

Glycogen synthesis:
Glucose converted to glucose-6P by hexokinsase + ATP

Glucose-6P is then converted to Glucose-1P by phosphoglucomutase

Glucose-1P combined with UTP and water forms UDP-glucose and PPi

UDP-glucose is then added to existing glycogen residues on the linear or branching chain

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5
Q

Glycogenolysis

A

Glycogen phosphorylase or a debranching enzyme breaks down glycogen(n residues) to glucose-1-P and Glycogen(n-1 residues)

The glucose-1-P is converted to glucose-6P and is either released by the liver into the blood for use by other tissues or its used up by muscles for energy production

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6
Q

Glycogen stores serve different functions in liver and muscle

A

G6P converted to glucose and exported to blood. Liver glycogen is a buffer of blood glucose level

Muscle lacks the enzyme Glucose-6-phosphatase. G6P enters glycolysis for energy production

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7
Q

Regulation of liver glycogen metabolism

A

Insulin and glucagon always oppose each other

Insulin inhibits glycogen mobilisation/ breakdown and stimulates glycogen synthesis

Glucagon/adrenaline vice versa

Muscle glycogen stores differ in that Glucagon has no effect.

Also AMP is an allosteric activator of muscle glycogen phosphorylase but not of the liver form of enzyme

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8
Q

Glycogen storage diseases

A

Inborn errors of metabolism (inherited diseases)

Arise from deficiency or dysfunction of enzymes of glycogen metabolism

12 distinct types. Incidence varies ~1 in 20,000 – ~1 in 100,000. Severity depends on enzyme/tissue affected

Liver and /or muscle can be affected

Excess glycogen storage can lead to tissue damage

Diminished glycogen stores can lead to hypoglycaemia & poor exercise tolerance

Examples: von Gierke’s disease - glucose 6-phosphatase deficiency
McArdle disease - muscle glycogen phosphorylase deficiency

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9
Q

Gluconeogenesis - the production of new glucose

A

Beyond ~ 8 hours of fasting, liver glycogen stores start to deplete and an alternative source of glucose is required: Gluconeogenesis

Occurs in Liver and to lesser extent in Kidney cortex

Three major precursors:
Lactate from anaerobic glycolysis in exercising muscle and RBC
Glycerol released from adipose tissue
Tissue BD of TGs

The AA is mainly alanine

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10
Q

regulation of gluconeogenesis

A

2 key enzymes regulated by hormones in response to starving fasting, prolonged excercise and stress -

insulin inhibits gluconeogenesis (therefore inhibiting the 2 enzymes) and vice versa with glucagon (and cortisol)

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11
Q

Lipid storage

A

Energy intake in excess of requirements is converted to Triacylglycerol (TAG ) for storage
TAGs are hydrophobic and therefore stored in an anhydrous form in specialised tissue – adipose tissue
Highly efficient energy store. Energy content per gram twice that of carbohydrate or protein
Utilised in prolonged exercise, stress, starvation, during pregnancy
The storage & mobilisation of TAGs is under hormonal control

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12
Q

Adipocytes

A

Contain Large lipid droplets (mainly TAG and cholesterol ester)

Cytoplasm and organelles pushed to edge.

Typical adipocyte ~0.1mm in diameter.

Cells expand as more fat added
Average adult ~30 billion fat cells weighing ~15 kg.

Can increase in size about fourfold on weight gain before dividing and increasing total number of fat cells

When obese person loses weight, in the period of time after, its quite easy to put that weight on, as adipocytes are still present to store fat

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13
Q

Overview of dietary TGs metabolism:

A

Ingest fat into GI tract - in SI fat is acted upon by pancreatic lipase to break fat down to FA and glycerol

Both are absorbed into epithelial cells, where these are reconstituted to form TGs, and then these are encorporated into a lipoprotein particle, called a chylomicrons (responsible for transport of dietary fat.

From here they drain into the lymphatic system (unusual as most nutrients from GI tract go into our blood), and will remain in lymphatic system until it drains into circulatory system.

First time this TG (dietary fat from chylomicrons) enter blood vessels is in the left subclavian vein

From here the TGs they either head to the adipose tissue where they are stored as TGs, or they can be utilised by tissues for energy

Fats are mobilised in adipose tissue by a hormone called by hormone sensitive lipase (regulated by insulin (-vely) glucagon and adrenaline (+vely)

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14
Q

FA synthesis - lipogenesis

A

Mainly in liver. Dietary glucose as major source of carbon.

Glucose

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15
Q

Comparison of FA synthesis and ß oxidation

A
FA oxidation:
Cycle of reactions that remove C2
C2 atoms removed acetyl CoA
Produces acetyl CoA
Occurs in mitochondria 
Separate enzymes 
Oxidative - produces NADH and FAD2H
Requires small amount of ATP to activate the fatty acid 
Intermediates are linked to COA 
Regulated indirectly by availability of FA in mitochondria 
Glucagon and adrenaline stimulate
Insulin inhibits 
FA synthesis:
Cycle of reactions that add C2
C2 atoms added as malonyl CoA
Consumes acetyl CoA
Occurs in cytoplasm
Multi enzyme complex 
Reductive - requires NADPH 
Requires large amount of ATP to drive process
Intermediates are liked to FA synthesis by carrier proteins 
Regulated directly by activity of Acetyl CoA carboxylate 
Glucagon and adrenaline inhibit 
Insulin stimulates
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16
Q

Fat mobilisation - lypolysis

A

Hormone sensitive lipase breaks down TGs in adipose tissue

Positive stim by adrenaline or glucagon , inhibition by insulin

This lipase BD TGs to glycerol and FA, glycerol is transported to liver, where tits converted to glucose

The free FAs can be used for energy production by Beta oxidation (transported in the blood attached to albumin