Intergration Flashcards
Consequences of high blood glucose on kidneys (4)
Rate of glomerular filtration (GFR) exceeds tubular reabsorption
And glucose appears in the urine
Results in osmotic diuresis
Which results in excessive urination and excessive thirst
Which tissues is glut 2 located (4)
Liver
Kidney
Intestine
Pancreas
Explain glut 2 km and activity
Km-7-20 mmol/l - high
Activity dependant on extracellular concentration of glucose
Which tissues is glut 3 located
Brain
Explain glut 3 km and activity
Km-1.6 mmol/l
Constant activity due to low km
Which tissues is glut 4 located (2)
Muscle
Adipose tissue
Explain glut 4 km and activity
Km-5 mmol/l
Activity dependent on insulin
Fate of glucose once it reaches cells (4)
Metabolised to provide energy in all cells (little in liver)
Converted to glycogen in muscle and liver
Converted to FAs and the TAG in liver and adipose tissue
Converted to ribose 5 phosphate and NADPH in all tissue
What is glucose first converted to when it enters a cell?
Glucose 6 phosphate
Fructose and galactose metabolism (2)
Majority converted to glucose in liver
Excess fructose may be converted into FAs
Major precursors of gluconeogenesis (3)
Lactate from muscle and erythrocytes
Glycerol from adipose tissue
AAs (alanine) from muscle
Why is TAG broken down and resynthesised?(2)
TAG is too hydrophobic to cross membranes
Re-esterification helps maintain conc gradient
Chylomicron pathway (4)
Travel from lymph to blood
TAG broken down by LPL
FAs taken up by cells
Chylomicron remnant taken up by liver
Where do FAs which are taken up by the liver come from?(3)
Newly synthesised by from carb precursors
Chylomicron remnants or escaped from tissue uptake
Released from adipose tissue
TAG synthesis in the liver (4)
Fatty acyl CoA + Glycerol 3 phosphate -> Lysophosphatidate
FA added to make phosphatidate
Phosphate removed to make DAG
FA added to make TAG
Transport of TAG from the liver (2)
Assembled into VLDL in hepatocytes
VLDL directly secreted into blood stream
Give some examples of ketone bodies (3)
Acetoacetate
3-hydroxybutyrate
Acetone
Why are FAs converted to ketone bodies?(3)
Ketones can be used by tissues which can’t use FAs
FAs not very soluble so conc kept low
Ketones are freely soluble
Enzyme that breaks down TAG to FAs in adipose tissue
Hormones sensitive lipase
Fed state and insulin effect (6)
Glucose uptake Increased LPL Increased FA uptake Increase synthesis of FA and glycerol 3 phosphate Increased TAG synthesis Decreased HSL
Fasted state glucagon and adrenalin effects (6)
Increase HSL Increased TAG breakdown Decreased glucose uptake Decreased FA and glycerol 3 phosphate synthesis Decreased LPL Decreased FA uptake
Which are the branched chain AAs (3)
Valine
Leucine
Isoleucine
How much of dietary AA uptake comes from branched chain AAs
20%
Oxidation of branched chain AAs (3)
Uptake of BCAAs by muscle specifically increased by insulin
Transaminated to 2-oxo acids
2-oxo-acids oxidised to CO2 and produces ATP
What enzyme in the muscle initiates the oxidation of 2-oxo-acid to CO2
2-oxo-acid dehydrogenase
AA inter-conversions in muscle (5)
Amino group from branches chain AA is transferred to oxo acid
Usual recipient of amino group is either pyruvate to form alanine
Or 2-oxoglutarate to form glutamate
Glutamate can be converted to glutamine by addition of NH2 group
Major AAs to leave muscle are alanine and glutamine
Glucose-alanine cycle (5)
Liver releases glucose which taken up by muscle
Glycogen broken down to pyruvate
Pyruvate is transaminated to alanine
Alanine transported to liver
This is then converted to pyruvate then glucose
Glucose liver uptake (3)
Liver has a high number of glucose transporters with high Km
Glucokinase has a high Km and is not inhibited by G6P
Therefore uptake is related to glucose concentration in blood
What enzymes are involved in the synthesis of glucose 6 phosphate?(2)
Hexokinase
Glucokinase
Hexokinase (2)
Located in most tissues
Inhibited by glucose 6 phosphate
Glucokinase (3)
Located in liver and pancreatic beta cells
Not inhibited by glucose 6 phosphate
Not insulin dependent
Dietary lipids (3)
TAG
glycerophospholipids
Cholesterol
Components of a chylomicron (4)
Re-esterified lipids
Free cholesterol
Lipid soluble vitamins
ApoB48
Components of VLDL (4)
TAG
Phospholipid
Free and esterified cholesterol
ApoB100
Which organ receives the highest glucose concentration?
Liver
Which tissues does gluconeogenesis occur?(2)
Liver
Kidney cortex
Endogenous lipoprotein pathway (6)
VLDL leaves liver and enters bloodstream
Lipoprotein lipase hydrolyses TAG
FA taken up by muscles and adipose tissue
VDL becomes IDL
IDL converted to cholesterol-rich LDL
Most of LDL goes to liver, some goes to other tissues such as arteries
What inhibits glycogen synthase?
Phosphorylation of the enzyme
Glycogen synthase is active when it is _______
Dephosphorylated
What activates glycogen phosphorylase?
Phosphorylation of enzyme
How are glycogen phosphorylase and synthase regulated during fed state?(5)
High insulin and low counter regulatory enzymes decrease kinase activity And increase phosphatase activity This activated glycogen synthase Inactivates glycogen phosphorylase Increases glycogen storage
Hormones that stimulates protein degradation (2)
Cortisol
T3
Hormones that stimulate protein synthesis (3)
Insulin
Growth hormone
Testosterone
What is the purpose of glucose-alanine cycle
Get rid of excess nitrogen
Branch chain AAs makes up ____ of the AAs leaving the liver after a meal
70%
In which tissues is there a high conversion of glucose to ribose 5 phosphate and NAPDH?(2)
Liver
Adipose tissue
Ketogenesis (3)
Occurs in liver
Acetyl CoA derived from oxidation of FAs are incorporated into ketone bodies
Can be used as a source of energy by most aerobic tissues
Glycogen synthesis (6)
G6P converted to G1P Using phosphoglucomutase G1P converted to UDP-glucose Using G1P uridyltranferase Glucose from UDP-glucose added to glycogen chain Using glycogen synthase UDP is released
Glycogenolysis (4)
Glycogen to G1P
By glycogen phosphorylase
G1P to G6P
By phosphoglyceromutase
Glycogenolysis liver (3)
G6P converted to glucose
Via G6 phosphatase
Glucose then enters blood
Glycogenolysis muscle (3)
G6P to pyruvate
Via glycolysis
Pyruvate is transaminated to alanine