Week 3 Flashcards
What is glycolysis
Converts glucose into 2 pyruvate molecules
Forms net 2 ATP
And 2 NADH from 2NAD+
Occurs in the cytosol
Glucose is primed with 2 phosphorylation steps and one isomerisation to form fructose-1,6-biphosphate which is then split to form glyceraldehyde-3-phosphate which is converted to pyruvate
What is gluconeogenesis
Reverses glycolysis, normally takes place in the liver
Synthesis of glucose from pyruvate
2 pyruvate, 4 ATP and 2 GTP and 2NADH make one glucose
Uses different enzymes
What two enzymes is regulation based on
In glycolysis- phosphofructokinase
In gluconeogenesis- 1,6,bisphosphatase
What is the Cory cycle
When lactate from skeletal muscle is taken up by the liver to go through gluconeogenesis to make glucose
Lactate produced by anaerobic respiration in muscles is transported to liver
In liver lactate is first converted into pyruvate
Pyruvate is the converted into glucose-6-phosphate (gluconeogenesis)
Glucose-6-phosphate is converted into glucose
Where does the citric acid cycle take place
In the mitochondrial matrix
What is the TCA cycle involved in
The breakdown of all three major food groups (carbohydrates, proteins and lipids)
What happens in the TCA cycle
Reaction oxidises pyruvate to CO2
Each cycle adds 2 carbon atoms as acetyl group and releases them in the form of CO2 however the carbons lost originate from oxaloacetate not acetyl CoA
The energy of acetyl CoA is stored in NADH and FADH2
What is NAD+ derived from
Vitamin niacin B3
What does NAD+ do
Acts as a coenzyme in several redox reactions
It’s oxidation in the respiratory chain generates 2.5 molecules of ATP
Nicotinamide adenine dinucleotide
What is FAD derived from
Vitamin riboflavin B2
What does FAD do
FAD attaches covalently to its enzyme
Succinate dehydrogenase contains FAD and is bound to the inner membrane of the mitochondria and is an integral part of the respiratory chain
FADs oxidation in succinate dehydrogenase generates 1.5 molecules of ATP
Flavin adenine dinucleotide
What are anaplerotic reactions
Reactions that fill in missing metabolites for important metabolic pathways
Examples of anaplerotic reactions in the TCA cycle
Direct conversion of pyruvate to oxaloacetate
Oxaloacetate/ aspartate conversion
Glutamate/ a-ketoglutarate conversion
Malate to pyruvate conversion (malic enzyme)
Where are the enzymes for the electron transport chain located
Inner mitochondrial membrane
Electron transport chain
When NADH gets oxidised it loses a proton and 2 electrons when the electrons leave NADH they’re high in energy each time they are passed on to one of the complexes they lose energy
This energy is used to pump protons from the mitochondrial membrane into inter membrane space
The proton gradient is then used to produce ATP
The transport of 2 electrons through complex 1 and 111 will extrude 4H+ each into inter membrane space
Charge separation across membrane etc
The electrochemical potential is 150-250mV
This potential difference provides the energy for ATP synthesis
3H+ ions are needed to make 1 ATP plus 1 H+ to translocate the ATP to the cytosol
What can cytochrome c oxidase (complex IV) be inhibited by
Complex IV catalyses the transfer of electrons to molecular oxygen
Inhibited by cyanide, carbon monoxide and azide
What is substrate level phosphorylation
Transfer of phosphate from a substrate to ATP (GTP)
What is oxidative phosphorylation
Formation of ATP coupled to oxidation of NADH or FADH2 by O2
How is energy converted to ATP
Energy from e- transport drives efflux of H+ from mitochondrial matrix
Proton electrochemical gradient formed
Proton gradient drives ATP synthase
The malate/ aspartate shuttle
Starts with cytosolic oxaloacetate
Malate dehydrogenase reduces OAA to form malate which is then transported into the mitochondria
Inside the mitochondria the reaction is reversed by the mitochondrial malate dehydrogenase
However as OAA is unable to cross inner mitochondrial membrane it has to be transaminated to aspartate which can be transported into the cytosol where its converted back into OAA by the cytosolic aspartate aminotransferase
What are uncoupling proteins
Provide proton channel allows H+ pumped into intramembrane space to go back into matrix
In brown adipose tissue
Energy released as heat
It’s a mitochondrial inner membrane protein that is a regulated proton channel
What else can be used to produce ATP
Fatty acids can be oxidised but slow process
Proteins can be broken down to release amino acids which can then be broken down further to produce ATP
Lactate
Control of metabolism
Primary control- the level of ATP
Levels of intermediates affect local rates
3 major control strategies - enzyme levels, enzyme activities (controlled by steroid regulation or product inhibition), substrate availability
Control of metabolism in TCA cycle
Pyruvate dehydrogenase
Isocitrate dehydrogenase
A-ketoglutarate dehydrogenase
Are all control points they are inhibited by ATP, NADH and acetyl CoA
Diseases associated with defects in carbohydrate metabolism
A range of diseases resulting from mitochondrial defects (neuro/visual symptoms) e.g. Leber hereditary optic neuropathy
Beriberi, mercury and arsenic poisoning
Diabetes, glucosuria
Glycogen storage disease
Cancer
What is diabetes mellitus
Imbalance between insulin and glucagon
High blood glucose , excessive ketone body production
Excess ketone body production leads to acidosis, coma, death
Insulin controls carbohydrate metabolism
ATP levels control insulin secretion
What are catabolic pathways
Break down complex molecules into simple molecules and release energy
What are anabolic pathways
Build complex molecules from simple molecules and require energy usually in form of ATP
Pyruvate decarboxylation
Link reaction- links glycolysis to TCA cycle
This is mediated by a large enzyme complex pyruvate dehydrogenase that converts pyruvate to acetyl-CoA
Occurs within mitochondria
NAD+ is reduced to NADH
One CO2 is produced
PDH complex made of pyruvate dehydrogenase, dihydrolipoyl transacetylase and dihydrolipoyl dehydrogenase
what happens when ATP is low or high
When ATP is low phosphofructokinase and glycolysis are switched on to generate ATP
When ATP is abundant phosphofructokinase is switched off and 1,6-biphosphatase is switched on driving ATP through gluconeogenesis to glucose
Products of TCA cycle
Acetyl CoA—> CoA+2CO2
3NAD+—> 3NADH
FAD—> FADH2
GDP +inorganic phosphate—>GTP (Substrate level phosphorylation)
Lactate fermentation anaerobic respiration
In anaerobic respiration NAD+ must be regenerated in order for glycolysis to continue
Pyruvate acts as hydrogen acceptor taking hydrogen from NADH catalysed by lactate dehydrogenase
Pyruvate is converted into lactate and NAD is regenerated
This can be used to keep glycolysis going so small amount ATP produced
Lactate is converted back to glucose in liver (gluconeogenesis) but oxygen needed to complete this process. Reason for oxygen debt and need to breathe heavily after exercise
Alcoholic fermentation anaerobic respiration
Non-reversible
Pyruvate is converted to ethanal (acetaldehyde) catalysed by pyruvate decarboxylase, 1 CO2 produced too
Ethanal can then accept a hydrogen atom from reduced NAD catalysed by alcohol dehydrogenases becoming ethanol
The regenerated NAD can the continue to act as coenzyme and glycolysis can continue
PDH complex regulation
The PDH complex is activated by dephosphorylation requires phosphatase
Enzyme deactivated by phosphorylation requires kinase
PDH complex converts pyruvate to acetyl CoA with production of CO2 and NADH
Carbon flux
Amino acids can be converted into acetyl CoA
Acetyl CoA can also be formed from fatty acids via beta oxidation pathway generally in mitochondria at inner membrane surface
When acetyl CoA levels are very high it can be converted into fatty acids for storage
Control of metabolism-GLUTs (glucose transporters)
An enzyme level mechanism controls uptake of glucose via GLUTs
Levels of GLUTs not static- dependent on tissue activity for example levels of GLUT4 will increase in muscles with endurance training
Different tissues have different GLUTs:
GLUT1- all mammalian tissues
GLUT2- liver cells, pancreatic B cells
GLUT3- all mammalian tissues
GLUT4- muscle cells and fat cells
Different GLUTs have different affinities for glucose, the lower the Km the higher the affinity for glucose so can take up glucose more easily
