(ignore) Energy Storage And Lipid Transport Flashcards
Energy stores in 70kg man
Triglycerides (Triacylglycerol) = 15kg
Glycogen = 0.4kg
Muscle protein = 6kg
Difference in energy stores in healthy end obese people
Glycogen and music protein= same
Triacylglycerols = much higher
Gluconeogenesis used when
When glycogen stores and therefore glucose stores are depleted
Glycogen structure
Highly branched polymer of glucose
Glucose residues joined by a1-4 and a1-6 glycosidic bonds
Adv of glycogen being highly branched
MAny sites where glycogen can be degraded back to glucose or more glycogen can be formed
Branch very 10 units
Glycogen stored where?
Liver + skeletal muscles in granules
Glycogenesis
Formation of glycogen from glucose
Glycogenesis steps = 4
1.) Glucose + ATP —-> Glucose 6-P + ADP
Catalysed by hexokinase (GLucokinase in liver)
2.) Glucose 6-P ——> Glucose 1-P
Catalysed by phosphoglucomutase
3.) Glucose 1-P + UTP + H2O —->UDP-glucose + 2Pi
UTP = Uridine Triphosphate is similar to ATP
4.) ????
Glycogen metabolism regulation
Enzymes in irreversible reactions in the pathways regulated
Glycogen synthase (biosynthetic pathway)
Glycogen phosphorylase ( Degradative pathway)
How is the activity of Glycogen synthase changed?
Inhibited by phosphorylation
Activated by dephosphorylation
How is the activity of Glycogen phosphorylase changed?
Inhibited by dephospharylation
Activated by phosphorylation
Glucagon and Adrenalines affect on glycogen synthase and glycogen phosphorylase
It increases phosphorylation
Therefore:
Glycogen synthase Inhibited (so less glycogen made)
Glycogen phosphorylase Activated (more glycogen broken down)
Glycogen synthase function
Joins glucose residues by a1-4 glycosidic bonds
What is the role of Glycogen phosphorylase?
Breaks down the a1-4 glycosidic bonds by phosphorylysis so residues released as glucose-1-phosphate
Insulins affect on Glycogen Synthase and Glycogen Phosphorylase
Causes dephosphorylation
Therefore:
Glycogen Synthase activated (Increased Glycogen production)
Glycogen Phosphorylase deactivated (Less Glycogen Breakdown)
Glycogen storage diseases
(Deficiency/Dysfunction of Glycogen synthase or glycogen phosphorylase)
So Increased/Decreased amounts of Glycogen:
-Tissue damage (Excessive storage)
-Fassting Hypoglycaemia
-Poor exercise tolerance
Abornormal glycogen structure
Liver and muscles are affected (where its stored)
Gluconeogenesis substrates
-Pyruvate, lactate and glycerol all convert to glucose
-Amino acids whose metabolism involves pyruvate or Krebs cycle intermediates can all convert to glucose
Gluconeogenesis Key control enzymes:
Fructose 1,6- bisphosphatase converts Fructose 1,6- bis phosphate to Fructose 6-phosphate and Pi (Phosphate)
PEPCK - Converts Oxaloacetate to Phosphoenolpyruvate
Glucose-6-Phosphatase (Converts Glucose-6-Phosphate to Glucose
How is Gluconeogenesis regulated?
Under Hormonal Control:
Regulatory enzymes that are affected are
-PEPCK
-Fructose 1-6 bisphosphatase
Insulin affect on Fructose 1-6 bisphosphatase (Key in Gluconeogensis)
Decrease amount of the enzyme Fructose 1-6 bisphosphatase
Insulin affect on enzyme PEPCK
Decreases amount and activity
Insulin affect on both Fructose 1-6 Bisphosphatase and PEPCK
Decreases amount of enzymes
Decreases activity of PEPCK
Glucagon and Cortisol affects on PEPCK and Fructose 1-6 bisphosphatase
Increased amounts and increase activity of PEPCK
Glucagon and Cortisol affect on Gluconeogenesis
Stimulates it
Insulins affect in Gluconeogenesis
Inhibits it
Triacylglycerols are efficient energy stores because:
-Stored in bulk in anhydrous form in adipose tissue
-Highly calorific (store lots of fuel molecules, fattty acids and glycerol)
Lipid/Triacylglycerol/Triglyceride storage under hormonal control.
Which hormones reduce its storage?
Which hormone increases its storage?
Glucagon, cortisol, adrenaline, growth hormone and thyroxine reduces its storage. Ensures it remains mobilised
Insulin Inncreases its storage
What is Lipogenesis?
Fatty acid synthesis
Where does lipogenesis occur?
Cytoplasm
What is the Basic idea of lipogenesis?
Acetyl CoA along with ATP and NADPH used to make fatty acids
Where does the NADPH come from that’s needed for lipogenesis
THE PENTOSE PHOSPHATE PATHWAY
(A type of metabolic pathway that glucose-6-phosphate undergoes)
Where does the Acetyl CoA come from needed for lipogenesis?
The Mitochondria
Citrate cleaved to oxaloacetate and acetyl CoA
What is the Fatty acid synthase complex ?
Multi enzyme complex that carries out most of the steps of lipogenesis
Acetyl CoA carboxylase
Enzyme that controls rate of fatty acid synthesis
Is not part of fatty acid synthase complex
Acetyl CoA carboxylase regulation
Modification of protein structure
Insulin activates. (Promotes its dephosphorylation)
Glucagon and adrenaline inhibit (Promotes its phosphorylation)
Most excess carbs and proteins converted to Triacylglycerols in adispose tissue
Excess = Type 2 diabetes and atherosclerosis
Fatty acid synthesis and fatty acid oxidation (B Oxidation) Are not reverse reaction of each other
Adv of catabolic and anabolic pathways occur in different routes:
-Greater flexibility (different substrates and intermediates)
-Better control
-Thermodynamically 8irreversible step can be by passed
Fatty acid synthesis
Cycles that add 2 carbons every time
Glucagon and adrenaline inhibit
Insulin stimulates
Fatty acid oxidation
Cycle of reactions that remove 2 carbons each time
Glucagon and adrenaline stimulate
Insulin inhibits
Classes of lipids
Triacylglycerols
Fatty acids
Cholesterol esters
Cholesterol
Phospholipids
Lipids insoluble in water
Transported in blood plasma associated with proteins
Lipoprotein particles
The highly specialised non covalent assemblies that transport lipids in the blood
Small amount of fatty acids carried non covalently bound to Albumin
The fatty acids came from lypolysis from adipose tissue
Apoprotein
The protein component of Lipoprotein Molecules
Package the non soluble lipid into a water lobule form
Hydrophobic region of apo protein interacts with lipid
Hydrophilic region of apoprotein interacts with water
Lipoprotein structure
Spherical
Surface coat/shell (Apoproteins, Phospholipids and cholesterol
Hydrophobic core (Triacylglycerols and cholesterol esters)
Classes of lipoproteins(Differ in composition of types of lipids and apoprotein comp)
Chlyomicrons
VLDL (Very Low Density Lipoproteins)
IDL (Intermediates Density Lipoproteins)
LDL (Low Density Lipoproteins)
HDL (High Density Lipoproteins)
Chlyomicrons function
Transport dietary Triacylglycerol from intestine to tissues like adipose tissues
VLDL
Transport Triacylglycerols SYNTHESISED in liver to adipose tissue for STORAGE
IDL
Transports cholesterol SYNTHESISED in LIVER to tissues
Precursor for LDL
LDL
Transport cholesterol SYNTHESISED in liver to tissues
HDL
Transports excess tissue CHOLESTEROL to liver for disposal as BILE SALTS
What is the function of Lipoprotein Lipase?
Where is it found?
What increases the amount of lipoprotein lipase?
What happens to the fatty acids and glycerols produced?
Removes core Triacylglycerols from Chlyomicrons and VLDLs
On inner surface of capillaries in adipose tissue and muscle
Hydrolyses Triacylglycerols. To fatty acids and glycerol. Fatty acids accepted by tissues glycerol taken to liver
Insulin increase synthesis of Lipoprotein Lipase
LCAT (Lecithin:Cholesterol Acyltransferase)
Converts some surface lipids to core lipids to balance out the ratio of surface to core lipids to ensure lipoprotein stability
What occurs as a result of LCAT Deficiency?
Unstable lipoproteins of abnormal structure
Lipid transport process fails
VLDL particles made in
Liver
LDLs (Low density Lipoproteins) clinical relevance
Susceptible to Oxidative Damage leads to formation of atherosclerotic plaques (build up of fats in/on artery walls)
Familial hypercholsterolaemia
Abscence/deficiency of function LDL receptors
Homozygotes have abscence so get atherosclerosis early in life
Heterozygous have deficiency so get atherosclerosis later in life
HDL Clinical relevance
HDL particles remove cholesterol and return it to liver as bile salts
This reduces likelihood of foam cells and atherosclerotic plaque formation
Dyslipoproteinaemias
Means any defect in metabolism of plasma lipoproteins
Primary dyslipoproteinaemia (familial inborn error of lipoprotein metabolism)
Secondary dyslipoproteinaemia (acquired through life)
Hyperlipoproteinaemias
Raised levels of plasma lipoproteins
Treating Hyperlipoproteinaemia
Diet and lifestyle modification (reduce eliminate cholesterol, reduce Triacylglycerol intake)
Statins (lowers plasma cholesterol. Reduces synthesis of cholesterol in liver by inhibiting HMG-CoA REDUCTASE )
Statins also increase expression of LIpoprotien lipase
Normal Blood Glucose Levels
5mmol/L
What level of blood glucose in Hypoglycaemia causes confusion
2.8mmol/L
Why is muscle glycogen trapped in the muscle?
How is glycogen used for energy?
Muscle has no Glucose - 6 - Phosphatase enzyme so it can’t be fully broken down into glucose so it is trapped in muscle
G6P enters glycolysis for energy production producing lactate
Liver Glycogen roles
Broken down in liver then released into the blood
Glycogen -> GLucose-1-phosphate ->Glucose
Glucose 6 Phosphate to glucose catalysed by Glucose-6-phosphatase
Glycogen storage disease examples
Von Gierkes disease (glucose-6-phosphatase deficiency) Liver can’t convert G6P to glucose so glucose trapped
McArdle disease - muscle glycogen phosphorylase deficiency (Glycogens 1-4 glycosidic bonds can’t be broken)
What is Glycogenin?
Protein dimer core of glycogen
What is the function of Pancreatic Lipase ?
Breaks down Triacylglycerides in smalle intestine into
Fatty acids + GLycerol
Intestine epithelial cells remake TAG
Which lipoprotein molecule then transports the TAG?
Chlyomicron
Malonyl CoA
