Glycolysis (Glucose Metabolism) Flashcards
state what it is meant by the key term - metabolism
metabolism is the total of all of an organisms life-sustaining chemical reactions
state what it is meant by the key term - metabolic pathway
a metabolic pathway is a series of steps found in biochemical reactions that help to convert molecules/substrates into different, more readily usable materials
state the names of the two types of metabolic pathways
- catabolic pathways
2. anabolic pathways
state what it is meant by the key term - catabolic pathways
a catabolic pathway is where a large molecule is broken down into it’s smaller molecules, and where energy is released
state what it is meant by the key term - anabolic pathways
an anabolic pathway is where small molecules are assembled into larger ones, and energy is required to do so
where is the location of: 1) glycolysis, 2) kreb’s cycle, and 3) the electron transport chain
- cytosol
- matrix of the mitochondria
- cristae of the mitochondria
state what it is meant by the key term - glycolysis
glycolysis is a series of reactions that extracts energy from glucose by splitting it into two 3 carbon molecules called pyruvate
how much glucose does the brain approximately use per day ?
approx. 190 grams
how much glucose does the body (excluding the brain) approximately use per day ?
approx. 160 grams
what are the two general steps of glycolysis termed ?
- energy requiring steps (first 5)
2. energy releasing steps (second 5)
1) what is the first step of glycolysis termed ?
2) what is the reaction ?
- phosphorylation of glucose
glucose+ ADP —– hexokinase ——> glucose-6-phosphate+ ATP
state 2 expansionary facts about the ‘phosphorylation of glucose’ step (1st) of glycolysis
- produces a more relative molecule
- as glucose-6-phosphate contains an ionised phosphate group, it becomes impermeable to the cell membrane (trapped inside the cell)
1) what is the second step of glycolysis termed ?
2) what is the reaction ?
- conversion of glucose-6-phosphate to fructose-6-phosphate
glucose-6-phosphate ——glucose phosphate isomerase ——> fructose-6-phosphate
state 2 expansionary facts about the ‘conversion of glucose-6-phosphate to fructose-6-phosphate’ step (2) of glycolysis
- doesn’t require an energy investment
2. isomerase: catalyses the rearrangement of an isomer (same chemical formula, different chemical structure)
1) what is the third step of glycolysis termed ?
2) what is the reaction ?
- phosphorylation of fructose-6-phosphate
fructose-6-phosphate + ATP ——–PFK———> fructose 1,6 bisphosphate + ADP
state 2 expansionary facts (relative to step 3 in glycolysis) about the PFK enzyme
- PFK is the rate limiting enzyme during glycolysis
2. there is a lot of PFK is fast twitch muscle fibres
state 2 expansionary facts about the ‘phosphorylation of fructose-6-phosphate’ step (3) of glycolysis
- prevents the re-formation of glucose-6-phosphate
2. 2nd phosphate allows 1 phosphate in each triose in step 4
1) what is step 4 of glycolysis termed ?
2) what is the reaction ?
- cleavage of fructose 1,6 bisphosphate
fructose 1,6 bisphosphate ——– aldolase —–> glyceraldehyde-3-phosphate (GAP) + dihydroxyacetone phosphate (DHAP)
state 2 expansionary facts about the ‘cleavage of fructose 1,6 bisphosphate’ step (4) in glycolysis
- GAP and DHAP are isomers
2. only GAP is able to continue down the glycolysis pathway
1) what is step 5 of glycolysis termed ?
2) what is the reaction ?
- isomerisation of DHAP to GAP
dihydroxyacetone phosphate (DHAP) ———-triose phosphate isomerase) ——> glyceraldehyde-3-phosphate (GAP)
state 2 expansionary facts about the ‘isomerisation of DHAP to GAP’ step (5) in glycolysis
- it is a rapid, and reversible, reaction
2. the reaction enables us to use both molecules in glycolysis
1) what is stage 6 in glycolysis termed ?
2) what is the reaction ?
- conversion of GAP to 1,3-diphosphoglycerate
glyceraldehyde-3-phosphate + NAD+ ——-glyceraldehyde-3-phosphate dehydrogenase ——-> 1,3-diphsphoglycerate + NADH
state 3 expansionary facts about the ‘conversion of GAP to 1,3-diphosphoglycerate’ step (6) in glycolysis
- GAP is oxidised and NAD+ it reduced to form NADH
- if low-mod intensity exercise, NADH used in aerobic metabolism
- if mod-high intensity exercise, pyruvate is reduced using NADH to form lactate
1) what is step 7 of glycolysis termed ?
2) what is the reaction ?
- conversion of 1,3-diphosphoglycerate to 3, phosphoglycerate
1,3-diphosphoglycerate + ADP ——–phosphoglycerate kinase——> 3, phosphoglycerate + ATP
state 2 expansionary facts to the ‘conversion of 1,3-diphosphoglycerate to 3, phosphoglycerate’ step (7) of glycolysis
- ‘substrate level phosphorylation’ is taking place
2. 2 x ATP re-synthesised as there is two branches going on simultaneously
1) what is step 8 of glycolysis termed ?
2) what is the reaction ?
- conversion of 3, phosphoglycerate to 2, phosphoglycerate
3, phosphoglycerate ——phosphoglycerate mutase———> 2, phosphoglycerate
state 2 expansionary facts about the ‘conversion of 3, phosphoglycerate to 2, phosphoglycerate’ step (8) of glycolysis
- mutase = moves the functional group
2. the phosphoryl group is being moved from the 3rd carbon molecule to the second carbon molecule
1) what is step 9 of glycolysis termed ?
2) what is the reaction ?
- conversion of 2, phosphoglycerate to phosphoenolpyruvate
2, phosphoglycerate ——-enolase——-> phosphoenolpyruvate + H2O
state 3 expansionary facts about the ‘conversion of 2, phosphoglycerate to phosphoenolpyruvate’ step (9) of glycolysis
- a water molecule is removed from 2, phosphoglycerate
- usually, an enzyme which removes water = dehydrolase
- this enzyme is called the old, established name as it produces a substituted enol
1) what is step 10 of glycolysis termed ?
2) what is the reaction ?
- conversion of phosphoenolpyruvate to pyruvate
phosphoenolpyruvate + ADP ——-pyruvate kinase——-> pyruvate + ATP
state 3 expansionary facts about the ‘conversion of phosphoenolpyruvate to pyruvate’ step (10) in glycolysis
- ‘substrate level phosphorylation’ takes place
- an irreversible step
- a net gain of 2ATP from glycolysis
state the 4 factors which control flux through glucose metabolism
- substrate availability
- enzyme concentration
- allosteric regulation
- covalent modification of enzymes
what is the uptake of glucose into cells regulated by ?
the uptake of cells is regulated by the GLUT family of transporter proteins
what is the location, and function, of GLUT 1 transporters ?
- RBC’s
2. controls basal glucose uptake
what is the location, and function, of GLUT 2 transporters ?
- Liver cells, Pancreatic Beta cells
2. uptake of glucose at a rate proportional to the amount of glucose present; removes excess glucose from the blood
what is the location, and function, of GLUT 4 transporters ?
- Muscle cells, Adipocytes
2. removes excess glucose from the blood; regulated by insulin
state 2 introductory facts about ‘enzyme concentration’
- the rate limiting enzymes of glucose metabolism catalyse the irreversible reactions
- the concentration of key rate limiting enzymes are regulated by the hormones insulin and glucagon
explain how insulin effects ‘enzyme concentration’
up-regulates the regulation of glucose enzymes: hexokinase, PFK and pyruvate kinase
explain how glucagon effects ‘enzyme concentration’ (3 points)
- down-regulates the expression of glycolytic enzymes and up-regulates the expression of gluconeogenic enzymes
- glucose-6-phosphatase and phosphoenolpyruvate carboxykinase
- glucagon also stimulates glycogenolysis
state what it is meant by the key term - allosteric regulation
allosteric regulation is the inhibition or activation of an enzyme by a small regulatory molecule that interacts at a site (allosteric site) other than the active site (at which catalytic activity occurs)
which 3 glycolytic enzymes do you need to know that get effected by allosteric regulation ?
- hexokinase
- PFK
- pyruvate kinase
explain allosteric regulation of hexokinase
- hexokinase is inhibited by glucose-6-phosphate and is termed: allosteric product inhibition
glucose + ATP ——hexokinase——–glucose-6-phosphate + ADP
- glucose-6-phosphate effects the enzyme that catalysed its formation
state the 4 locations of the 4 hexokinases you need to know
hexokinase 1: brain
hexokinase 2: muscle and adipocytes
hexokinase 3: kidney
hexokinase 4: liver (glucokinase)
where is glucokinase active and inactive ?
- > 5mM - glucokinase active (localised in the cytosol)
2. <5mM - glucokinase inactive (localised in the nucleus)
what is PFK inhibited by ? (allosteric regulation)
ATP and Citrate (from the Kreb’s cycle)
what is PFK activated by ? (allosteric regulation)
AMP (from the liver) and fructose-6-bisphosphate
PFK is a bifunctional enzyme…
- PFK2
2. fructose 2,6 bisphosphatase
in liver cells, what is PFK primarily regulated by ?
in liver cells, PFK is primarily regulated by sugar levels
in skeletal muscle cells, what is PFK primarily regulated by ?
in skeletal muscle cells, PFK is primarily regulated by ATP and AMP levels (ADP + ADP –>
how is pyruvate kinase allosterically regulated ?
- pyruvate kinase is regulated by a feedforward mechanism by fructose 1,6 bisphosphate
phosphoenolpyruvate ——pyruvate kinase—–> pyruvate
- fructose 1,6 bisphosphate activates pyruvate kinase action
- ATP and Acetyl CoA inhibits pyruvate kinase action
what 4 gluconeogenic enzymes do you need to know get effected by allosteric regulation ?
- glucose-6-phosphatase
- fructose 1,6 bisphosphate
- phosphoenolpyruvate carboxylase
- pyruvate carboxylase
explain how fructose 1,6 bisphosphatase is allosterically regulated in gluconeogenesis
fructose 1,6 bisphosphate —-fructose 1,6 bisphosphatase —–> fructose-6-phosphate + Pi
- citrate activates
- AMP and Fructose 2,6 bisphosphate inhibit
explain covalent modification of pyruvate kinase (5 points)
- low blood glucose inhibits H2O –> P, and activates ATP –> ADP
- increases phosphorylated pyruvate kinase (less activated)
- more of that, increases dephosphorylation to dephosphorylated pyruvate kinase (more active)
- more of that, more phosphorylated is produced …
- negative feedback
