Module 6: V1 - V6 Flashcards
What do anabolic pathways involve?
building cell macromolecules from simpler precursor molecules
What do catabolic pathways involve?
breaking down energy-containing nutrients into energy-depleted end products
What is the function of CoA?
functions in acyl transfer reactions where X is an acetyl, acetoacetyl or other group which is transferred to another molecule
Where is Acetyl-CoA used?
central to metabolism; used in Krebs cycle, fatty acid synthesis/oxidation etc.
What is Acetoacetyl-CoA used for?
the switch to “ketone bodies” during starvation
What are critical molecules that are involved in metabolism derived from?
dietary vitamins
What are the two phases of glycolysis?
preparatory and payoff phase
What is the first reaction of glycolysis? What enzymes is this reaction catalysed by?
phosphorylation of glucose
glucose -> glucose-6-phosphate
hexokinase in most tissues and glucokinase in the liver
Is the first reaction of glycolysis reversible or irreversible?
irreversible
What is the second reaction of glycolysis? What enzyme is this reaction catalysed by?
isomerisation of glucose-6-phosphate -> fructose-6-phosphate
phosphohexose isomerase
Is the second reaction of glycolysis reversible or irreversible?
reversible
What is the third reaction of glycolysis?
conversion of fructose-6-phosphate -> fructose-1,6-bisphosphate
Is the third reaction of glycolysis reversible or irreversible? What is significant about the third reaction?
irreversible
rate limiting step of glycolysis
What is the fourth reaction of glycolysis? What enzyme is this reaction catalysed by?
cleavage of F-1,6-bP
aldolase cuts the F-1,6-bP in the middle, producing DHAP and GA-3-P
What is the fifth reaction of glycolysis? What enzyme is this reaction catalysed by?
isomerisation of DHAP to glyceraldehyde-3-phosphate
triose phosphate isomerase pulls a H atom off one C atom and replaces it on a neighbouring C atom
How many ATP are produced during the preparatory phase?
there is a net loss of 2 ATP in the preparatory phase of glycolysis
What is the sixth reaction of glycolysis or the first reaction of the payoff phase? What enzyme is this reaction catalysed by?
oxidation of glyceraldehyde-3-phosphate to 1,3-biphosphoglycerate
catalysed by glyceraldehyde 3-phosphate dehydrogenase
What does activity of glyceraldehyde 3-phosphate dehydrogenase depend on?
the turnover of NAD+ in the cytosol of the cell under anaerobic conditions
What is the seventh reaction of glycolysis? What enzyme is this reaction catalysed by?
conversion of 1,3-biphosphoglycerate to 3-phosphoglycerate
PGK transfers the phosphate from 1,3-BPG to ADP to form ATP
What is the eighth reaction of glycolysis? What enzyme is this reaction catalysed by?
conversion of 3-phosphoglycerate to 2-phosphoglycerate
PG mutase shifts phosphate from C3 of the PG molecule to C2 priming it for phosphate transfer to ADP
What is the ninth reaction of glycolysis? What enzyme is this reaction catalysed by?
dehydration of 2-phosphoglycerate to phosphoenolpyruvate
enolase converts 2-PG to PEP
What is the tenth reaction of glycolysis? What enzyme is this reaction catalysed by?
production of ATP from the conversion of PEP to pyruvate
pyruvate kinase
What is gained per glucose during glycolysis?
net energy gain of 2 ATP and 2 NADH per glucose, which is equivalent to ~5 ATP per glucose
Why are some chemotherapeutic agents used to inhibit hexokinase in treating cancer?
because glycolysis proceeds up to 10x faster in cancer cells
How can high glycolytic turnover in cancer cells be used for diagnosis?
by injecting isotopically labelled glucose followed by PET scanning
What is the Warburg Hypothesis?
most cancer cells produce energy by anaerobic glycolysis rather than by oxidation of pyruvate in the mitochondria (which is common to healthy cells)
Is gluconeogenesis the reverse of glycolysis? Why?
no
because irreversible steps occur in glycolysis and different enzymes need to be used
What is the enzyme used in the 1A bypass step in gluconeogenesis? What does it do?
pyruvate carboxylase
adds a carboxylic acid to pyruvate to form oxaloacetate using biotin as a cofactor
What is the enzyme used in the 1B bypass step in gluconeogenesis? What does it do?
phosphoenolpyruvate carboxykinase which converts oxaloacetate -> phosphoenolpyruvate upon addition of GTP
What is the enzyme used in the 2 bypass step in gluconeogenesis? What does it do?
fructose-1,6-bisphosphatase
converts fructose-1,6-biphosphate to fructose-6-phosphate
What is the enzyme used in the 3 bypass step in gluconeogenesis? What does it do?
glucose-6-phosphatase
converts glucose-6-phosphate to glucose
What is the final product of glycolysis?
pyruvate
What are the five major fates of pyruvate?
ethanol, lactate, alanine + pyruvate which moves into the mitochondria and becomes either oxaloacetate or acetyl CoA
What is the important role of lactase dehydrogenase?
under anaerobic conditions plays an important role in regenerating NAD+ for STEP 6
What are typical energy stores in humans?
adipose TAG -> 84%
mobilised proteins -> 15%
glucose/glycogen -> 1%
What is glycogen?
storage form of carbohydrate in the body which is critical during fasting as liver glycogen provides a source of blood glucose
Can muscle glycogen give rise to blood glucose? What is it used for instead?
no
used to power muscle contraction for extended periods of time
What is glycogenolysis? Which enzymes does this process involve?
the breakdown of glycogen
glycogen phosphorylase, debranching enzyme and phosphoglucomutase
What is glycogenesis? Which enzymes does this process involve?
the synthesis of glycogen
UDP-glucose pyrophosphorylase, glycogen synthase and amylo transglycosylase (glycogen-branching enzyme)
How does debranching enzyme get rid of branches on a glycogen particle?
transfers a block of 3 glucose residues to a nearby nonreducing end and then hydrolyzes the a1->6 linkage to release free glucose
What is the role of phosphoglucomutase?
transfers phosphoryl group on glucose-1-phosphate from C1 to C6 to form glucose-6-phosphate, which is freely reversible
What causes marathon runners to “hit the wall”
body runs out of available glycogen storages
What is the role of UDP-glucose pyrophosphorylase?
synthesizes UDP-glucose form UTP and glucose-1-phosphate and also produces pyrophosphate (PPi)
What is the role of glycogen branching enzyme?
catalyses transfer of 6/7 glucose residues from the nonreducing end of a glycogen branch having at least 11 residues to the C6 hydroxyl group of a glucose residue in a more interior position within the same or a different glycogen chain
What is the role of glycogenin?
glycogen synthase cannot initiate synthesis of a new glycogen chain since it requires a primer
glycogenin is both the primer on which new chains are synthesized and the enzyme that catalyses their assembly
Is glucose oxidised during glycolysis?
yes, glucose is oxidised into two molecules of pyruvate
Animals don’t photosynthesise, but can we make carbohydrates? What do we make carbohydrate from and where do we get the energy to do so?
yes, carbohydrate is made from pyruvate and energy required to complete this process comes from the TCA cycle
Why do we export lactate from the muscles?
prevents lactic acidosis during anaerobic conditions in the muscle
Why don’t we just transport ATP around the body? Surely this would be a lot easier?
ATP is ionized because of its phosphate groups, and therefore doesn’t travel through cell walls readily
