Revsion Lecture Semester 2 Flashcards
How are primary monosacs abs
Via carrier mediated mechanisms which demo stereo specificity, saturation kinetics and can be specifically inhibited
What is SGLT1 and what dos it do
Sodium- glucose linked transporter mem bound proetin binds glucose and sodium at diff sites - symporters driven by conc grad of these two
also transport galactose
What is an example of secondary active trans
SGLT1 trans galactose
What does GLUT2 do
Uni porter transports monosacs into circulation facilitated
Where is SGLT1 found
Luminal mem of enterocyte
How is the sodium gradient maintained
Maintained by sodium potassium ATPase which keeps intracellular sodium conc low
What is the driving force of sodium transport
Sodium conc grad set up by ATPase also brings glucose
How is facilitated sugar transport mediated
By members of the glut transporter family
What is glycogenesis
Synthesis of glycogen from glucose
What is Glycogenolysis
Breakdown of glycogen to form glucose
What is gluconeogensis
Syn of glucose in body from non- carb precursors such as amino acids, lactic acid and glycerol
What is glycogen
Main storage form of glucose in liver and muscle cells
What is liver glycogen used for
Broken down between meals and released to maintain the brain and blood levels for red blood cells
What is muscle glycogen used for
Not available for maintenance of blood glucose levels
Provides energy via glycolysis and the TCA cycle during bursts of physical activity
What are the bonds of glycogen
Alpha 1-4 glycosidic links - between glucose molecules
Alpha 1-6 glycosidic bonds - introduce branches
What enzyme is used to convert glucose to glucose 6 Phosphate
Hexokinase
What enzyme converts glucose 6 Phosohate to glucose 1 phosphate
Phosphoglucomutase
What is glucose 6 phosphate used in
Glycolysis
What is glucose - 1 - phosphate used for
Glycogen synthesis
What does glycogen synthesis require
Primer which contains at least 4 glucose residues
Made up by convalently attached to glycogenin
What is activated glycogenin
Uses UDP-glucose - activated glucose
What enzyme is used in UDP glucose formed
UDP glucose pyrophosphorylase
What is the reactions of UDP glucose formation
UTP + glucose 1 phosphate –> UDP glucose + pyrophosphate
Is UDP glucose reversible
Yes
How is glycogen syn by UDP glucose
Via glycogen synthase rate limiting step
What does glycogen synthase do to glucose mole
Add one glucose mol to glycogen at a time forming alpha 1-4 glycosidic bond
Can only extend chains not new branches
What is the branching enzyme
Transglycosylase introduces alpha 1-6 glycosidic branches to glycogen
When does glycogenesis occur
Immediately after meals when blood glucose increased
What is the importance of cholesterol
Essential component of mammalian cell membranes as reg fluidity
Precursor of 3 imp classes of bio active compounds
Imp for metabolism
Why is cholesterol imp for metabolism
CVD
Component to gall stones
What is cholesterol the precursor of
Bike acids
Steroid hormones
Vitamin D
What kind of solubility does cholesterol have in water
Low
How much of circulating cholesterol is in the free form
30%
What are cholesterol esters and what is their solubility like in water
Majority esterified to a wide range of long chain fatty acids they are esterified through cholesterol hydroxyl
Less soluble in water
How are cholesterol esters stored and where
Lipid droplets in ER
What is cholesterol incorporated in
Lipoproteins
Present as free cholesterol and cholesterol esters which are located in the core of molecule
How does fee cholesterol control its own synthesis
Negative feedback regulator
How is the regulation of cholesterol controlled
Mediated by a family of transcription factors (DNA binding) STEROL REGULATORY ELEMENT BINDING PROETINS -SREBS
What are SREBS
Regulate syn of enzymes which control prod of cholesterol
HMG CoA reductase
HMG CoA synthase
Also codes for cell surface receptor
APOPROTEIN RECEOTOR
What does the deletion of hepatic sterols do to SREBS
Increases SREBS and therefore increases cholesterol syn and expression of APOPROTEIN receptors
What is the APOPROTEIN receptor recieve
Cholesterol in form of lipoprotein
What are some features of endocarp sis
Receptor mediated
Specific saturable
Movement into cell
E.g binding of LDL
What are some properties of exocytosis
Secretory
Movement out of cell
E.g when chylomicrons carrying tags or cholesterol Etc
Leave enterocyte and enter lacteals
What is the primary function of lipoproteins
Transport vehicles for lipids in lymph and blood
What is the structure of a lipoprotein
Core hydrophobic lipids - cholesterol esters and tags
Surrounded by shell- polar lipids whic are phospholipids, apoproteins, free cholesterol
How are lipoproteins distinguished
By size and density
More lipid the lower density
The more proetin the higher density
Explain some properties of low density lipoproteins
Major lipid - cholesterol
Delivers cholesterol to cells for cell mem and hormone prod
LDL receptor is mem bound proetin which binds LDL causing is to be taken up by cell and dismantled
Explain some properties of high density lipoproteins
Major lipid - phospholipid
Syn by liver snd intestine
Circulates blood to collect excess cholesterol
What are high density lipoproteins important for
Reverse cholesterol transport
Salvages excess cholesterol form cells
Chol then esterified with fatty acids
Trans back to liver
Excreted as bile salts via biliary system or faeces
What is the only organ capable of metabolising and excreting cholesterol
Liver
Where does cholesterol synthesis occur
In the cytoplasm but some enzymes bound to ER mem
Main site syn is liver but also lesser contributions form intestine, adrenal Cortex, gonads
What dos the synthesis of 1 mole of cholesterol require
Source of C atoms
- 18 moles of acetyl coA
A source of reducing power
- 16 moles nADH
Significant amount of energy
- 36 atp
What is mevalonic acid
3 moles of acetyl coA are converted into 6-carbon mevalonic acid
What enzymes are used in acetyl coA reactions
Acetoacetyl coA thiolase
HMG-coA synthase
HMG-coA reductase (rate limit step of chol syn)
What is the rate limiting step of chol syn
HMG-coA reductase
Formation mevalonic acid irreversible
What is HMGR
HMG-coA reductase
Where is HMGR found
Embedded in ER
How is HMGR controlled
Feedback inhibition
Rate of deg
Phosphorylation
Gene expression
What hormones affect HMGR
Insulin and T3 - increase activity
Glugacon and cortisol - inhibit activity
What does a high intracellular free cholesterol lead to
Limit syn by HMG-coA reductase activity
Limit uptake by down reg of LDL receptors
Increase in efflux
Increased rate of conversion to bile salts
How much of free cholesterol obtained form diet
15%
What do statin drugs do
Inhibit cholesterol syn
What does the inhibition of cholesterol synthesis lead to
Leads to increase in LDL receptor expression
Promotes removal of LDL form blood
What is the main metabolic product from cholesterol
Bile salts
How do bile salts differ
In number and position of hydroxyl groups
Where are bile salts syn and sec
Liver
How are the four primary bile acids formed
Before secretion
Cholic acid and chenodeoxycholic acid are conjugated though Carboxyl to glycine or taurine
Where are bile salts stored
Gall bladder
What do bile salts do
Sec and into duodenum act as detergents for emulsifying ingested lipids
What does vitamin D do
Play a role in regulation of calcium/phosphorous metabolism
How is vitamin D3 synthesised
In the skin by uv light from the sun of 7-dehydrocholesterol
What is the active form of Vit D3
Calcitriol
Steroid hormone
What are the three organs that convert cholesterol into steroid hormones
Adrenal cortex - corticosteroids
Testis- androgens
Ovary - estero gens
How do steroid hormones act
Binding to specific receptors
Zinc fingers next to DNA binding domain of hormone
Binging hormone facilitates translocation of activated receptor
What is the gene transcription by glucocorticoids
Steroid binds to receptor in cytoplasm
receptors dimerises
Exposes a nuclear localisation signal
Enters nucleus
Binds DNA at specific response element which is a hormone response element
Activate promoter and switch transcription on or off
What does the transformation of cholesterol to bile acids and steroid hormones include
Hydroxylaction reactions catalysed by cytochrome P450 mono oxygenate
Give some examples of primary mono sacs
Glucose fructose and galactose
