5 Energy Storage (glycogen and fat) Flashcards
Tissues with absolute requirement for glucose
-RBCs - no mitochondria
-lens of eye
-neutrophils - located in areas of low O2
-innermost cells of kidney medulla - low O2 environment
Outline glycogen storage
Stored as granules
- muscles - 300mg only be used by muscles, no glucose 6 phosphate
-liver 100mg used to buffer plasma glucose
Glycogenesis definition
Synthesis of glycogen
Anabolic-reducing
Is glycogenesis reducing or oxidative?
Anabolic so reducing
Glycogenolysis definition
Breaking down glycogen to glucose
Two examples of glycogen storage disease
1- Von Gierke’s disease: glucose 6 phosphate deficiency
2- McArdle disease: muscle glycogen phosphorylase deficiency
Consequence of increased glycogen storage
Tissue damage
Consequence of decreased glycogen storage
Hypoglycaemia
Poor exercise tolerance
Gluconeogenesis definition
Production of new glucose from an originally non glucose source
After 8 hours of fasting
Where and when does gluconeogensis occur?
Mainly liver
Partially in kidney cortex
~ 8 hours of fasting
What are the non glucose sources in gluconeogensis?
- amino acids: mainly alanine
- glycerol: release from adipose tissue-breakdown of triglycerides
- lactate: from anaerobic respiration
What is the cori cycle?
Lactate being used as a non glucose source in gluconeogensis
1- muscles used up glucose
2- lactate is produced in anaerobic respiration
3- lactate transported to liver in blood
4- glucose made in liver via gluconeogensis
3 key enzymes involved in gluconeogenesis
PEPCK
Fructose 1,6 phosphatase
Glucose 6 phosphatase
Which enzymes are regulated in gluconeogensis and how?
PEPCK and fructose 1,6 phosphatase
Stimulated by glucagon and adrenaline - glucose needed in times of starvation and stress
Inhibited by insulin - glucose not needed
When are lipids used as an energy source?
-prolonged exercise
-stress
-starvation
-during pregnancy
How are TAGs stored?
-hydrophobic
-stored in anhydrous form - no osmotic effect
-in adipose tissue
How can you identify adipose in a H&E stain?
-white fat broken down during fixation
-nucleus and cytoplasm pushed to side
Lipogenesis definition
Fatty acid synthesis
Where are fatty acids synthesised?
Liver
What is the regulator enzyme in lipogenesis?
Describe the regulation
-acetyl CoA carboxylase
- inhibited by glucagon,adrenaline and AMP: acetyl CoA needed for respiration
- stimulated by insulin+citrate
What does the fatty acid synthase complex do?
Additions of 2C units from malonyl CoA (from beta oxidation) to make fatty acids
Lipolysis definition
Fat mobilisation
How are fatty aids transported to muscle?
In the blood
Albumin complex
Weight and energy content of TAG in healthy 70kg man
15kg
600,000kJ
Weight and energy content of TAG in obses 135kg man
80kg
3,000,000kJ
Glucose synthase function
Adds glucose molecules onto existing branches on glycogen making a1-4 glycosidic bonds
Branching enzyme function
Creates new branches off of glycogen from the formation of a1-6 glycosidic bonds
Hexokinase/glucokinase function
-kinase: adds a phosphate group
Glucose > glucose 6 phosphate
Glucokinase in liver
Phosphoglucomutase function
Reversible reaction of G6P to G1P
G1P uridyl transferase function
Transfers phosphate group on G1P to UDP
G1P > UDP glucose
Glycogen phosphorylase function
Breaks a1-4 glycosidic bonds in the chains of glycogen
De-branching enzyme
Breaks a1-6 glycosidic bonds on glycogen branches
Why does insulin stimulate fatty acid production?
Lots of glucose > lots of glycolysis > lots of acetyl CoA > acetyl CoA made into malonyl CoA to make fatty acids
Why can’t glycogen stored in muscles be used to raise blood sugar?
They don’t have glucose 6 phosphatase
Signs and symptoms of baby with Von Gierke’s Disease
- protuberant abdomen (looks like a potato) from heptaomegaly as glycogen is deposited in liver and not broken down fully
- sweating and pallor from hypoglycaemia
- high blood fatty acids from gluconeogensis to compensate for low blood glucose
Normal blood glucose range
4-6 mmol/L
What is the role of insulin on lipogenesis?
Stimulates fatty acids synthesis via dephosphylation of acetyl CoA carboxylase
What is the renal threshold for glucose?
10mmol/L
Describe the molecular structure of glycogen
a 1-4 glycosidic chain bonds
a 1-6 glycosidic branch bonds
Outline the steps in glycogenesis
Glucose + ATP > glucose 6 phosphate + ATP
hexokinase/glucokinase
Glucose 6 phosphate > glucose 1 phosphate
phosphoglucomutase
Glucose 1 P + UTP + H2O > UDP-glucose + Pi
uridyl transferase
Glycogen (n residues) + UDP-glucose > glycogen (n+1 residues) + UDP
glycogen synthase / branching enzyme
Outline glycogenolysis
Glycogen (n residues) + Pi > glycogen (n-1 residues) + glucose 1 P
*glycogen phosphorylase / debranching enzyme)
Glucose 1 P > glucose 6 P
phosphoglucomutase
Glucose 6 P > released into blood as glucose (liver)
> used for glycolysis (muscle)
What is the rate limiting enzyme for glycogenolysis?
Glycogen phosphorylase
What is the rate limiting enzyme in glycogenesis?
Glycogen synthase
What effect does glucagon + adrenaline have on the rate limiting enzymes in glycogen metabolism?
Mechanism: phosphorylation
Decreases glycogen synthase
Increases glycogen phosphorylase
What effect does insulin have on the rate limiting enzymes in glycogen metabolism?
Mechanism - dephosphorylation
Increases glycogen synthase
Decreases glycogen phosphorylase
How do glycogen storage diseases occur?
Arise from deficiency or dysfunction of enzymes or glycogen metabolism
Why can glucose not be made from acetyl CoA?
Acetyl CoA can’t be converted to pyruvate
PDH reaction is irreversible
Outline lipogenesis
In liver
+oxaloacetate
Glucose > pyruvate > acetyl coA > citrate
Citrate > acetyl coA + oxaloacetate in cytoplasm
Acetyl coA > malonyl coA
acetyl coA carboxylase
Malonyl coA + 2C units > fatty acids
fatty acid synthase complex
Outline lipolysis
Triacylglycerol > glycerol + fatty acids
hormone sensitive lipase
What is the regulation of lipolysis
inhibited by insulin > phosphorylation
stimulated by glucagon + adrenaline > dephosphorylation
