Glycogen & Fat Flashcards
What regulates gluconegensis?
Hormonal control, that acts on2 major sites,
PEPCK and fructose 1,6-bisphosphate
Glucagon/cortisol stimulates gluconeogenesis > increasing their amount
Insulin inhibits it» decreasing their amount
**insulin/glucagon ratio plays an important role in determinging the rate of gluconeogenesis
Ok
Relate diabetes and its effects on gluconeogenesis
Diabetes, have less insukin, so glycogenogemsis will be stimulated and this causes hyperglycemia
What effect does insulin and glucagon have on lipid storage?
I sulin stimulates its storage
Glucagon inhibits it
What happens our glucose level drops below 0.6mmol/L?
Brain damage-death
it what situation do you see hypoglycaemia?
-athletes gone so much activity
**MUSCLE GLYCOGEN STORES DOES NOT HAVE A RECEPTER FOR GLUCAGON!
So glucagon mainly work son liver
What r the 3 main precursers of gluconeogenesis? where did they come from?
Lactate> from aerobic glycolysis in muscle
Glycerol> breakdown product of TAG
aa» mainly alanine
***Acetyl-CoA cannot be converted into pyruvate (pyruvate dehydrogenase reaction is irreversible) so there is no net synthesis of glucose from acetyl-CoA
Got it
What type of recepters does, insulin, glucagon, cortisol bind to?
insulin- tyrosine recepter
Cortisol- nuclear
Glucagon- GPCR
Which fat soluble vitamin plays an important role in protecting cells against oxidative damage by acting as a free radical scavenger?
Vit E (α-tocopherol) plays an important role in protecting cells against lipid peroxidation. Vitamin C (Ascorbic acid) is a water soluble antioxidant that plays an important role in regenerating the reduced form of Vitamin E.
Describe the key features of electron transport and explain how
the proton motive force (p.m.f) is produced.
In Electron transport electrons are transferred from NADH (and FAD2H) sequentially through a series of multi-component complexes to molecular oxygen with the release of free energy. The free energy is used to move protons from the inside to the outside of the inner mitochondrial membrane. The membrane itself is impermeable to protons and as electron transport proceeds the proton concentration on the outside of the inner membrane increases. The chemical bond energy of the electrons is transformed into an electro-chemical potential difference of protons. This is known as the proton motive force (p.m.f).
Explain how the relationship btw ETC & atp synthase is altered during thermogenesis in brown
adipose tissue mitochondria.
The inner mitochondrial membrane of brown adipose tissue has, in addition to the ATP synthase complex, a special proton conductance protein (thermogenin) that allows the controlled re-entry of protons into the mitochondrial matrix without driving ATP synthesis i.e. it acts to uncouple ATP synthesis from ET. This protein is used to activate heat production (non-shivering thermogenesis) in cold environments.
How does NE play a role in thrmogenisis in brown adipose tissue relating to the ETC and Atpase?
1) In response to cold, noradrenaline is released from the sympathetic nervous system and stimulates lipolysis releasing fatty acids to provide fuel for oxidation in brown adipose tissue.
As a result of B-oxidation of the fatty acids, NADH and FAD2H are formed, driving ET and increasing the p.m.f.
2) NE also activates thermogenin allowing the protons to re-enter the mitochondrial matrix without driving ATP synthesis. This dissipates the p.m.f as heat.
which structures need an absolute fuel of glucose as an energy source?
RBC
neutrphills
inner most cells of kidney medulla
lens of eye
**To enable blood glucose to be kept at required levels, a store of glucose is required…GLYCOGEN
ok
how is glycogen stored and where?
as granules in
- muscle glycogen
- liver glycogen (in hepatocytes)
which body tissue contains the greatest amount of glycogen in terms of mass?
skeletal muscle
how many hrs btw meals does glucose have to be formed via Gluconeogensis?
(8-12hrs)
describe glycogen structre
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 a-1-4 glycosidic bonds with a-1-6 glycosidic bonds forming branch points every 8-10 residues
describe the steps of glycogen synthesis…
Step 1. Glucose + ATP —> glucose 6-P + ADP
catalysed by hexokinase (glucokinase in liver)
Step 2. Glucose 6-P ----->Glucose 1-P catalysed by (phosphoglucomutase)
Step 3. Glucose 1-P + UTP + H2O —–>UDP-glucose + 2Pi
Step 4. Glycogen (n residues) + UDP-glucose glycogen (n + 1
residues) + UDP
does glycogen synthesis require energy?
yes
describe process of Glycogenolysis in liver and muscle cells
Glycogen—> Glucose 1-P —> Glucose 6-P
Then if in liver glucose 6-P becomes Glucose via G6 phosphatase.
BUT
In muscle that enzyme is not there, so G6P will undergo glycolysis
**glycogenolysis is Not reversal of glycogenesis!!
Different enzymes r involved!
is glycogen degraded completely?
no, a bit of it is always reserved
key enzymes in glycogen degradation
- glycogen phosphorylase (debranching enzyme)
- phosphoglucomutase
IN LIVER ONLY
Glucose 6- phosphatase
rate limiting enzymes in glycogen synthesis and degradation in LIVERRRR, and effects of Glucagon/adreniline and insulin.
how does this differ in muscle glycogen stores?
-glycogen synthase
**insulin increases activity
Glucagon decreases
-glycogen phosphorylase
**glucagon inreases
insulin inhibits
**Muscle glycogen stores differ in that Glucagon has no effect.
what effect does glucagon have on muscle glycogen stores?
NONE
what r the Glycogen Storage Diseases?
- Inborn errors of metabolism (inherited diseases)
- Arise from deficiency or dysfunction of enzymes of glycogen metabolism.
describe clinical consequences of glycogen storage diseases!
- Liver and /or muscle can be affected
- Excessive glycogen storage leads to tissue damage
- Diminished glycogen stores can lead to hypoglycaemia in blood & poor exercise tolerance
define Gierke’s disease & McArdle disease
-glucose 6-phosphatase deficiency
(Enlargement of liver bc they cant release the glycogen)
-glycogen phosphorylase deficiency
(they become exhausted, bc they can’t break down glycogen stores from muscle)
enzymes involved in glycogen metabolism.
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Glycogen stores serve different functions in liver and muscle, differentiate btw them,
LIVER» G6P converted to glucose and exported to blood. Liver glycogen is a buffer of blood glucose levels.
MUSCLE» Muscle lacks the enzyme Glucose-6-phosphatase. so G6P enters GLYCOLYSIS for energy production
what is Gluconeogenesis? where does it occur?
production of new glucose from non carb molecules.
in the liver and shwaya bl kidney cortex
Key enzymes in Gluconeogensis?
1) PEPK
ocaloacetate–>phosphophenylpyruvate
2) Fructose 1,6 biphosphatase
F1,6 Biphos–>F6P
3) Glucose-6-phosphatase
G6P–> Glucose
Regulation of gluconeogenesis
mention the enzymes involved
2 key enzymes regulated by hormones in response to:
• Starvation/fasting
• Prolonged exercise
• Stress
- PEPCK
- Fructose 1,6 bisphosphatase
which effect would Glucagon have on the enzymes glycogen synthase in the liver
Decrease actvity
what effect would insulin have on the enzyme PEPCK?
decreases its amount
Inhibits it
(insulin Dont wanna make more glucose gosh no, they wanna store them)
how is there a link in the Krebs cycle and Gluconeogenesis
we used oxaloacetate in the process. which came from Glucogenic aa and lactate
describe the time Course of Glucose Utilisation. (where ur body gets glucose over time)
starting with when u first eat meal.
U EAT
Glucose from food
~2 Hours
Glycogenolysis
Up to 1-10 hours
Gluconeogenesis
8-10 hours onwards
why r TAGS an efficient store of energy more than anything else?
TAGs are hydrophobic and therefore stored in BULK in an anhydrous form
when do we break down Lipid storages?
In PROLONGED aerobic exercise, stress, starvation, during pregnancy
** The storage & breakdown of TAGs is under hormonal control.
Name the hormonal effects on it
n
where r lipids stored?
Adipose tissues (adipocytes)
When obese patient loose a lot of weight, it is difficult to keep that weight off, why?
bc adipocytes note only expand when they have a lot of fat in them, but they reach to a point where they’ll start DIVING as well.
& in obese ppl, they have a lot of adipocytes that want to fill themselves with TAG!
how does TAG travel from the intestines to the bloodstream?
via chylomicrons, it enters the lymphatic system and drains into the L. Subclavian vein into the thoracic duct then into the blood.
Look at overview of dietary TAG metabolism in lecture
ok
If u consume sugar rich diet, what happens to the excess sugar that is not being used for energy?
is converted and stored as FAT.
where does fatty acid synthesis occur? (lipogenesis) what is its precursor?
it occurs in the liver
dietary glucose
explain the process of fatty acid synthesis.
notes
what r the key enzymes involved in fatty acid synthesis?
acetyl-CoA carboxylase
convert Acetyl Coa into Malonyl-CoA ( which in needed to add 2 carbon chains to the growing fatty acid tails)
how and where does lipolysis occur? what is the key enzyme here?
in adipose tissue, TAG broken down via hormone sensitive LIPASE.
compare fatty acid synthesis and fatty acid oxidation.
table in lecture.
in lipogenesis, what adds 2 carbon chains to the fatty acid?
Malonyl CoA, adds 2 carbon to the growing FFA chain, and this is done via the FATTY ACID SYNTHASE COMPLEX
What is gluconeogenesis and why is it necessary? Name the
hormones that stimulate the process and those that inhibit it.
Gluconeogenesis is the production of glucose from precursors such as lactate, pyruvate, glycerol and certain amino acids. It is necessary to provide glucose for glucose-dependent tissues such as the CNS and red blood cells during starvation when the liver stores of glycogen have been exhausted.
Insulin inhibits gluconeogenesis
Cortisol and glucagon stimulate gluconeogenesis
Compare and contrast the functions of liver and skeletal muscle
glycogen.
Glycogen is converted to G1P then to G6P
In muscle, the G6P enters glycolysis and is used to provide ENERGY for the exercising muscle. Thus, muscle glycogen represents a store of glucose 6- phosphate that can only be used by the muscle cells.
In liver during fasting or during stress the G6P is converted to GLUCOSE by the enzyme glucose 6-phosphatase (this enzyme is absent from muscle):
Compare and contrast triacylglycerols and glycogen as energy
storage materials in humans.
TAGare the major energy storage molecules in the body (a 70kg man would normally store 10-15kg compared to 0.4 kg of glycogen).
TAG stored in highly specialised tissue (adipose tissue)
glycogen is stored in tissues such as the liver and skeletal muscle.
TAG more efficient from of energy storage as they are hydrophobic and are stored in an anhydrous form while
glycogen is polar and is stored with water.
In addition, triacylglycerols are more reduced that glycogen and contain more stored energy per C-atom than glycogen.
What are the major energy stores in a 70kg man and when are
they used?
Glycogen»_space;used during the overnight fast, and as part of the response to stress and exercise.
🍟TAG» used in starvation, as part of the response to stress, during the third trimester of pregnancy, during lactation and during prolonged aerobic exercise (marathon running).🚴🏽
🍗Protein is used only in an EMERGENCY during starvation.
Describe, in outline, the processes that enable the triacylglycerols
stored in adipose tissue to be used by skeletal muscle cells.
O
List the products that can be synthesised from acetyl~CoA and explain why it cannot be converted to glucose in humans.
- fatty acids
- co2
- hydrocymethyl glutamic acid
it can’t be converted to pyruvate in man bc the enzymes pyruvate dehydrogenase is irreversible, sooooo since it cannot be converted to to pyruvate,it cannot be converted to glucose!
Explain why the process of fatty acid synthesis (lipogenesis) is not
simply a reversal of the process of fatty acid degradation (-
oxidation).
The process of fatty acid degradation is an exergonic process and involves reactions that are not IRREVERSIBLE in the cell. Thus, the process cannot be easily reversed in the cell. The process for fatty acid synthesis must therefore use different reactions.
Explain how tissues obtain the lipids they need from
lipoproteins.
P
Explain how lipids are transported around the body.
Hydrophilic lipids are transported in association with mprotein:
~98% as specialised lipoprotein particles
~2% bound non-covalently to albumin (fatty acids)
Lipoprotein particles consist of non-covalent assemblies of triacylglycerols, phospholipids cholesterol, cholesterol esters and protein.
There r 5 major classes
Chylomicrons transport dietary lipids (mostly triacylglycerols).
VLDLs transport lipids (triacylglycerols) synthesised in the liver.
IDLs are a short-llived precursor of LDL
LDLs transport cholesterol synthesised in the liver.
HDLs transport cholesterol from peripheral tissues to the liver for
disposal
Explain why individuals with a defect in the enzyme lecithin-
cholesterol acyltransferase produce unstable lipoproteins of
abnormal structure. What are the clinical consequences of this
defect?
P
Which plasma concentration of total cholesterol would you consider normal for a healthy person?
Less than 5mM (5mmol/L) is the ideal total cholesterol concentration
which tissues do u find glucokinase? hexokinase?
Glucokinase» liver
Hexokinase
