Lecture 3 - Energy Storage glycogen and fat Flashcards

1
Q

what is hypoglycemia ?

A

low blood sugar levels

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2
Q

how and why do we store glucose within the body ?

A

some cells require glucose for energy - RBC’s, Neutrophils, lens of the eye

we need to be able to keep some glucose even during starvation - so we store it as glycogen - so these cells at minimum have glucose to function

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3
Q

how and where is glycogen stored ?

what does it look like in imaging ?

A

musclular glycogen - it is stuck within the muscle - only the muscle cells can use this

intermyofibrilar glycogen - edges of the sarcomeres

intramyofibirilar glycoen - within sarcomeres

both are still black granules

Liver glycoen - black granules of glycogen storage used to replenish bodys plasma glucose levels - within hepatoctyes

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4
Q

what is the structure of glycogen ?

why is it advantageous for storage ?

A

highly branched molecule - polymer of glucose residues

a1-6 form the branch points , a1-4 form the chain extension

its nature provides storage as a large macro molcule with no osmotic effects

highly branched - allows for lots of release of lots of glucose from many points simultaneously - allows for the rapid synthesis or breakdown of glycogen

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5
Q

outline the process of glycogenesis

A

glycogen synthesis

glucose —– to G-6-P with hexokinase (1st step of glycolysis) - uses ATP

G-6-P feed out of glycolysis to G-1-P
phosphoglucomutase

G-1-P + UTP + H2O —-> UDP glucose + 2Pi

Glycogen is then extended with UDP glucose by glycogen synthase (1-4 extension) or branching enzyme (1-6 branch) - this step is irreversible

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6
Q

outline the process of glycogenolysis

draw a outline of how glycogen use is different in the muscle and liver

A

glycogen degregation

glycogen + Pi ——> G-1-P + glycogen(-1n)

uses glycogen phosphorylase for (1-4 chain reduction)
and
De-branching enzyme (1-6 branch breakage)

G-1-P is converted to G-6-P with phospoglucomutase

in the muscles it can be used in glycolysis (as they lack g-6-P phosphotase)

in the liver G-6-P is converted to glucose and released into the blood for other tissues to use

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7
Q

why do we have both glycogenisis and glycogenolysis ?

A

so we have different enzymes allowing for simultaneous inhibition of one path and stimulation of the other path

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8
Q

draw a outline of glucose metabolism and check against lecture 3

A

do it

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9
Q

how is liver glycogen metabolism regulated ?

check lecture

A

glycogen synthesis - rate limiting enzyme is - glycogen synthase

glycogen degradation - rate limiting enzyme is - glycogen phosphorylase

glucagon/adrenaline - increase glycogen degradation via glycogen phosphrylase and decrease glycogen synthase activity - decrease glycogen sysnthesis

both are phosphorylated

insulin - dephosphorylation of both synthase and phosphorylase - will increase synthase / synthesis

will decrease - phosphorylase / storage

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10
Q

how does muscle metabolism differ to liver metabolism

A

glucagon has no effect

AMP is an allosteric activator of muscle glycogen phosphorylase

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11
Q

outline glycogen storage diseases

A

12 types

due to disfunction or deficieny of enzymes of glycogen metabolism

can affect liver and/or muscle
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 - hepatomegaly - caused by glycogen build up
• McArdle disease - muscle glycogen phosphorylase deficiency- severe fatigue in exercise

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12
Q

what is gluconeogenesis ?

A

8 hours past eating we deplete glycogen stores so we must synthesise new glucose

occurs mainly in the liver and abit in the kidney cortex

three pre cursors feed into gluconeogenesis

Lactate - cori cycle - anaerobic glycolysis in muscles and RBC’s produces lactate - transported to liver and converted to glucose for distribution - allows muscle to dispose of lactate

Glycerol released from adipose tissue via the breakdown of triglycerides

glucogenic amino acids such as alanine

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13
Q

what are the key enzyme steps in gluconeogenesis

A

glucose - 6- phosphotase - converts G-6-P to glucose

  1. Fructose 1,6-bisphosphatase converts Fructose 1,6-bisphosphate to fructose - 6 - phosphate
  2. Phosphoenolpyruvate carboxykinase (PEPCK)

uses GTP —-> GDP + CO2
to convert oxaloacetate to phospoenolypyruvate

1 + 2 are the major control points of the pathway

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14
Q

outline the regulation of gluconeogenesis with a table and the key enzmyes

A

check against lec 3 when done

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15
Q

what is the purpose of lipid storage ?

A

it is a high density energy storage

glycerol and fatty acids combine to make triacylglycerol

where we store our excess energy as fat - stored in adipose tissue - they are hydrophobic so stored in anhydrous adipose tissue

utilised in starvation, exercise ect

storage and mobilisation of TAG’s are under hormonal control

adipocytes are white single fat droplets - when we gain weight we divide to produce more fat cells, this explains why it is easier to put back on weight

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16
Q

outline TAG metabolism

may be useful to draw

A
  1. eaten
  2. broken down in small intestine to Fatty acids and glycerol
  3. recombines to a TAG in inestinal epithelial cells, taken up by chylomicrons (a particle that solublises TAGS for transport)
  4. travels through the lymph system, before entering blood at the thoracic duct at the left sub clavian vein
  5. blood can drop off and can be stored in adipose tissue
  6. or utilised for energy via fatty acid oxidation
  7. hormone sensitive lipase (stim by glucagon and adrenaline, inhibt by insulin) will release TAG into blood transported by FA-Albumin (the mobilisation of Fats)
17
Q

briefly what is beta oxidation

A

fatty acid breakdown to acetyl CoA

18
Q

outline fatty acid synthesis (lipogenesis)

again may help to draw a diagram

A

occurs mainly in liver

glucose —> pyruvate

pyruvate —-> acetyl CoA and OAA in mitochondria
condense to from citrate

citrate exits mitochondria to cytoplasm - breaks back inot acetyl CoA and OAA

the key regulator acetyl CoA carboxylase produces manonyl CoA from acetyl CoA

fatty acid synthase complex builds fatty acids by sequential addition of 2 carbon units provided by malonyl CoA

uses ATP and NADPH

19
Q

what is the key regulator of lipogenisis

A

Acetyl-CoA carboxylase = Key regulatory enzyme
Insulin (covalent de-phosphorylation), & citrate (allosteric) increase activity
Glucagon / adrenaline (covalent phosphorylation) & AMP (allosteric) decrease activity

20
Q

use lecture 3 to compare fatty acid synthesis and B oxidation

A

they are reverse process’ of each other

maybe youtube it ?

21
Q

fat mobilsation (lipolysis) outline it

may help to draw

A

within adipose tissue - HSL stimulates release into the blood

Glucagon & Adrenaline leads to phosphorylation and
ACTIVATION of HSL (hormone sensitive lipase)

Insulin leads to dephosphorylation and INHIBITION of HSL

in the blood it is broken down into free fatty acids and glycerol can be used in B oxidation and gluconeogenisis