Glucose & Carbohydrates Flashcards
What is the usual fasting range of glucose?
4-6 mmol/l
How long after eating does it take for glucose levels to normalise?
2-3 hours
Name 3 glucose dependant cell types
Neurons, Erythrocytes, Mammary Glands, Testis
Why is glucose homeostasis important?
Allows for a supply of energy to the cells dependant on glucose as their only form of energy source -> i.e. hypoglycaemia could cause N&V, seizure, coma or death due to the brain not being able to synthesise energy/ATP as glucose is not available.
Also important in preventing hyperglycaemia which also has negative effects -> CVD risks, DM complications, Inflammation
What are the 4 main pools of glucose in the body?
Blood
ECF
Liver Glycogen (70-120g)
Skeletal Muscle Glycogen (200-1000g)
Give an example of a glucose transporter that is dependant on insulin? Also where are these commonly found?
GLUT4 - these are commonly found in muscle and adipose tissues
Give an example of a glucose transporter that is independant of insulin? Also give an example of where this is found in the body
GLUT 1,2,3 or 8 - these are found in the glucose dependant cells so neurons and erythrocytes but also found in the liver
Give the 3 ways of how to get glucose levels to increase?
Digestion & Absorption of dietary carbs
Glycogenolysis
Gluconeogenesis
Give the 3 ways to reduce glucose levels
Glycolysis
Glycogenesis
Conversion of glucose into fat acids and amino acids
What does an item with a high glycaemic index mean?
Contains a greater proportion of digestible carbohydrates than non-digestible
What transporter is involved in monosaccharide absorption?
SGLT-1 = glucose and galactose
GLUT 5 = fructose
What is the difference between SGLT1 & GLUT5?
SGLT-1 is active transport
GLUT5 is facilitated transport
Where does absorbed monosaccharides go from the enterocyte?
Portal vein via GLUT2
Where does monosaccharides go once in the portal vein?
Goes to the liver where some glucose is taken up by the liver (approx. 30%) and then rest remains in circulation
How many steps are there to glycolysis?
10
What is the start and end of glycolysis
1 glucose -> pyruvate
What are the 3 key enzymes in glycolysis and why are they important / pointed out in the lectures?
The following 3 enzymes are involved in 3 of the 10 steps in glycolysis and make them non-reversible and are rate limiting
Hexokinase, Phosphofructokinase, Pyruvate Kinase
What are the end products of glycolysis if in anaerobic and aerobic conditions and where do they go?
Anaerobic -> lactic acid -> Cori Cycle
Aerobic - acetyl CoA -> citric acid cycle
What two options does acetyl CoA have following glycolysis?
Enters CAC to allow for oxaloacetate to become citric acid and enter the aerobic respiration pathway
Or the acetyl CoA can be utilised in fatty acid synthesis
How does fructose and galactose metabolism differ from glucose?
Fructose enters the glycolysis pathway at a different stage - it becomes monophosphorylated to F1P (fructose monophosphate) and then enters glycolysis later on in the pathway
Galactose is converted to G1P then G6P which enters the Leloir Pathways
What is unique / special about fructose in reference to its entry to glycolysis pathway?
It misses on of the rate limiting enzymatic steps, therefore there is less regulation as to how much fructose enters the pathway
Other than glycolysis what other pathway is glucose commonly used in?
Pentose Phosphate Pathways
What is the function of the Pentose phosphate pathway?
Two functions:
1st function is to produce NADPH to help alleviate the cells from oxidative stress (i.e. during the formation of the compound it mops up free radicals)
2nd function is to produce ribose sugars used in DNA synthesis
What is the main chemical reaction that outlines the function of the pentose phosphate pathway
Glucose 6 Phosphate + NADP -> Ribose-5-Phosphate + NADPH
How does glucose enter the PPP?
Glucose is converted to G6P in the first step of glycolysis and then this is 2 routes -> either enter the glycolysis or PPP pathway
Give a cell that depends on the PPP in practise?
Erythrocytes -> these undergo lots of reductive reactions producing lots of free radicals and oxidative stressors like H2O2
This is why it is linked to congenital anaemias
I.e. in glucose-6-phosphate dehydrogenase (G6PD) deficiency the enzyme that is required to convert G6P to the ribose-5-phosphate is missing, impaired / not functioning so therefore unable to produce NADPH and the cells undergo excessive oxidative stress resulting in haemolytic anaemia / favism
What is gluconeogenesis?
Formation of glucose from non-carbohydrate sources
What are the main sources of substrates used in gluconeogenesis?
Lactate -> cori cycle
Alanine / Amino acids
Glycerol from fatty acids
How does lactate become glucose in gluconeogenesis?
Cori Cycle -> lactate can be converted back to pyruvate and move up the glycolysis pathway
How does amino acids become glucose in gluconeogenesis?
Alanine is the main amino acids and this like lactate can be converted to pyruvate and move u[ the glycolytic pathway
How does fatty acids convert to glucose in gluconeogenesis?
The glycerol from FAs can be converted to acetyl CoA and then converted to pyruvate and move up the glycolytic pathway
Where does gluconeogenesis take place in the body?
Liver and Kidneys
What does the “reverse of glycolysis” mean in reference to gluconeogenesis
The reverse of glycolysis is how non-carbohydrate compounds are converted to glucose once they become pyruvate
How is gluconeogenesis regulated?
3 types of mechanisms:
Allosteric
Genetic Expression Mechanisms
Covalent Phosphorylation
What do the regulating mechanisms do to allow or gluconeogenesis to take place?
Forms key enzymes / allows for access of key enzymes that can reverse the 3 steps that are ‘non-reversible’ oin the normal glycolysis pathway
Name 2 key enzymes in gluconeogenesis
Glucose-6-phosphatase
Fructose-1,6-biphosphatase
PEP carboxykinase
Pyruvate Carboxylase
What is glycogenesis
Synthesis of glycogen
Where does glycogenesis take place?
Liver & Skeletal Muscle
What is glycogen?
A branched polysaccharide / polymer of glucose
What is the structure of glycogen
Straight chains of alpha-1,4- glycosidic bonds with alpha 1-6 glycosidic bond branching every 9-10 units
What are the two key enzymes in glycogen synthesis and degradation?
Glycogen Synthase
Glycogen Phosphorylase
What is the detailed explanation of glycogen synthesis?
Glycogenin acts as an enzymatic primer for the first few glucose monomers to attach to.
This enzyme then undergoes autoglycosylation to form proglycogen
Glycogen synthase then takes over to form macroglycogen (55,000 glucose subunits)
What is important to remember about glycogen and glycogen synthesis?
High energy costs
High water binding capacity
Where is glycogen stored?
Cytosol of cells
What is the main stimulator for glycogenesis?
Insulin
What is glycogenolysis
Glycogen degradation to produce glucose
WHat enzyme mediates glycogenolysis
Glycogen phosphorylase
How is glucose produced from glycogen?
Glycogen Phosphorylase cleave the glycosidic bonds and attaches a phosphate to each glucose unit to form glucose monophosphate (G1P).
This is then isomerised to G6P
G6P is then able to convert back to glucose via glucose-6-phosphatase or go down the glycolysis pathway
Name 2 things that down regulates glycogenolysis
Glucose, G6P, F1P, ATP, ADP,
What is the difference between liver and skeletal muscle glycogenolysis?
Liver is more responsive to external stimuli such as hormones and blood glucose concentration
Skeletal muscle is more responsive to allosteric stimuli such as AMP (the break down product of ATP), G6P.
What situations upregulates glycogenolysis?
Stress -> exercise, hypoglycaemia, hypoxia
How does catelcholamines upregulate glycogenolysis?
Catecholamines are able to phosphorylate glycogen phosphorylase to its active form via activation of PKA - protein kinase A
What is the endocrine proportion of the pancreas collectively called?
Islet of Langerhans
What do alpha, beta and delta cells produce in the pancreas?
Alpha = Glucagon Beta = Insulin Delta = Somatostatin
What is the structure of the insulin hormone?
51 amino acids in two polypeptide chains
What is the half life of insulin
5mins
How is insulin secreted into the blood?
Beta Cells have GLUT2 transporters to allow plasma glucose enter the cells by facilitated transport
Increased glucose entry means more can undergo glycolysis so therefore increased ATP production
High ATP concentration closes voltage gated K channels to build up K conc. inside cell resulting in membrane depolarisation opening Ca2+ channels, causing Ca2+ influx.
This results in insulin granule exocytosis
How is insulin secretion stopped?
Low glucose in the plasma, results in less entering the pancreatic beta cells via GLUT2 facilitated transport. This lowers ATP production within these cells
This allows for K channels to remain open, keeping the membrane potential of the cell hyperpolarised so no conformational changes can happen to the Ca2+ channels meaning no influx and therefore no exocytosis of insulin granules
What pattern can be used to describe insulin secretion?
Explain the theory behind it
Biphasic
Phase 1 : transient wave in first 5-8 mins
Phase 2 : gradual rise over a longer period
Theory is that the first wave = membrane bound vesicle release and phase 2 = central vesicle release
How else does glucose and carbs help regulate insulin secretion?
Theory is that glucose and carbs can directly impact insulin gene expression & increase synthesis
How does fatty acids and amino acids affect insulin secretion?
FAs = short term increases, long term inhibits AAs = increases secretion
What are the functions of the incretin hormones?
GLP-1 & GIP indirectly stimulate insulin secretion via g-protein coupled receptors when glucose levels are high
What is GLP-1 and GIP?
Glucagon-Like-Peptide-1
Gastric inhibitory peptide
Give 3 sites of action for insulin
Liver, Skeletal Muscle, Adipose Tissue
What is insulins activity in skeletal muscle? (2)
Increases glucose uptake via GLUT4 (insulin dependant transporter) and promotes glycogenesis.
What is insulins activity in liver? (3)
Promotes glycogenesis, glycolysis
Promotes lipogenesis, TAG & Cholesterol synthesis
Suppresses gluconeogenesis, beta-oxidation. ketogenesis
What is insulins activity in adipose tissue? (3)
Aids TAG removal from plasma
Aids TAG synthesis
Prevents fat mobilisation
What is the structure of the glucagon hormone?
29 AA single polypeptide chain
What is the intermediate compound called that is actually secreted from the pancreatic cells?
Proglucagon
How does glucagon act on cells (generically)
Via transmembrane G protein coupled receptors
What stimulates glucagon release?
Low glucose and amino acids
Name 3 actions of glucagon
Glycogenolysis
Gluconeogenesis
Ketogenesis