Liver and gluconeogenesis Flashcards
Why is glucose used?
The requirement for glucose is continuous
* Glc is the preferred fuel source for all tissues
* some tissues have a continuous dependence on glucose
What is the blood glucose concentration in the human body?
- physiological circulating glc concentration 3.9-6.2 mM
- average fasting 4.4-5 mM for most adults
- if it drops to 2.5 or less coma and death can result
- if it rises for an extended time, dehydration, wasting of body tissue and eventually death will result
What is the roles of glucose?
- It is a source of energy
glucose → pyruvate gives 2 ATP
glucose → CO2 + H2O gives 31 ATP - it is a source of NADP
- needed for synthetic reactions (fatty acids, steroids) and drug metabolism
- it is a source of pentose sugars for for synthetic reactions (nucleotides, DNA )
- it is a source of carbon for other sugars and glycoconjugates (mannose,galactose, glucuronic acid
What are advantages of glucose as a metabolic fuel?
- Water soluble , so does NOT require a carrier in the circulation
- can cross the blood-brain barrier
- can be oxidised anaerobically
What are disadvantages of glucose as a metabolic fuel?
- relatively low yield of ATP/mole compared to fatty acids
- osmotically active
- In high concentrations can directly damage cells or lead to accumulation of toxic by-products (fructose, sorbitol)
What are Pathways involving glucose
- all tissues use glucose
- the liver can provide glc for other tissues
What is the role of glucose in skeletal muscle?
glycolysis - Anaerobic muscle contraction
Glycolysis/TCA cycle - energy
Glycogen synthesis and degradation - Energy store for
muscle contraction
What is the role of glucose in heart/brain muscle?
Heart/brain
Main Pathway - Glycolysis/TCA
Function - ENERGY
What is the role of glucose in Adipose tissue?
Adipose tissue
Main pathway - glycolysis
Function - Production of glycerol P’ for TAGS
What is the role of glucose in Erythrocyte?
Tissue - Erythrocyte
Main pathway - glycolysis
Pentose phosphate pathway
(shunt)
Energy - NADPH
What is a role of glucose in the liver?
Function of the pathways?
What are the sources of blood glc?
- Diet
- Liver Glycogen
- Liver gluconeogenesis
What is Gluconeogenesis?
In conditions of carbohydrate deprivation glc is synthesised from non-carbohydrate sources in the liver
* Lactate
* glycerol
* other monosaccharides
* glucogenic amino acids (all except leu, lys)
* NOT FROM FATTY ACIDS
What is the irreversible reaction of gluconeogenesis?
gluconeogenesis is not simply the reversal of glycolysis
There are 3 irreversible reactions in glycolysis that must be bypassed.
They are catalysed by:
* hexokinase/ glucokinase
* phosphofructokinase
* pyruvate kinase
- all in the cytosol
Role of Pruvate Kinase?
pyruvate kinase catalyses the conversion of PEP to pyruvate
pyruvate carboxylase and PEP carboxykinase are needed for the conversion of pyruvate to PEP in gluconeogenesis
Regulation of gluconeogenesis
- Mobilisation of substrate
– glycerol from fat breakdown
– amino acids from muscle protein breakdown - activation of enzymes
– G6Pase F1,6bisPase,PEPCK
(insulin/glucagon is low)
– activation pyruvate carboxylase by acetyl CoA
What is blood glucose maintenance?
- Insulin, glucagon and adrenaline (and to a lesser extent cortisol) and glucose itself, signal and co- ordinate the activities of
– liver
– adipose tissue – muscle tissue - Maintain physiological blood glc concentrations needed to preserve brain function (and other tissues dependent on glc)
Describe?
Islets of Langerhans in the pancreas
- beta cells secrete insulin
- alpha cells secrete glucagon
What is the different between insulin and glucagon?
- insulin is an anabolic hormone. It promotes synthesis and storage
- glucagon is a catabolic hormone. It promotes degradation of stored fuel
Sites of insulin action on metabolism
What is metabolic effects of insulin: Liver?
- Inhibition of gluconeogenesis
- activation of glycogen synthesis (glycogen synthase activated)
- Increased Fatty Acid synthesis and lipid assembly
- Increased aa uptake and protein synthesis
What is the process of the liver in the fed state?
Metabolic effects of insulin: Muscle
- Increased glucose uptake by increasing glucose transporters (GLUT4)
- Increased aa uptake and protein synthesis
- activation of glycogen synthesis (glycogen synthase activated)
What is the process of the muscle: FED STATE?
What is process of MUSCLE: AEROBIC?
What is the Metabolic effects of glucagon?
- increase in blood glucose
– ↑ glycogenolysis and gluconeogenesis (liver). - Increase in circulating fatty acids and ketone bodies
– ↑ adipose tissue lipolysis, ↑fatty acid oxidation in the liver and ketone body formation. - Decrease in plasma amino acids
– ↑uptake by the liver for gluconeogenesis.
What is the LIVER: FASTING STATE?
BRAIN: FED OR FASTING
ERYTHROCYTE : FED OR FASTING
