Energy, Metabolism, ATP, Glycolysis, Acetyl CoA, Mitochondria, OXPHOS Flashcards
what is anabolism?
the synthesis of new molecules from less complex compounds
what is catabolism?
the breakdown of complex molecules into simpler molecules for the release of energy
why do people study metabolism?
- to understand the metabolic basis of diseases like diabetes
- to understand how the diseased state changes how body uses food
- to understand diseases
- changes in metabolites can aid diagnosis
what is ATP in terms of energy?
- is the body’s energy provision
- it can act as both an acceptor or donator of energy
- it is a short term reservoir of energy
what regulates glycolysis?
- reversible binding of allosteric effectors
- covalent modification
- transcription
how much ATP do we use at rest?
40kg/24hours
how much ATP does the body have?
100g
what are the major oxidative pathways?
- glycolysis
- citric acid cycle
- ETC to OXPHOS
- fatty acid oxidation
how is glucose converted to pyruvate?
- glucose is phosphorylated by hexokinase to form G6P using ATP
- phosphofructokinase (PFK) converts G6P to fructose-6-phospahte using ADP
- fructose-6-kinase is converted to fructose-1,6-bisphosphate by PFK
- fructose-1,6-bisphosphate is converted to two C3 molecules (dihydroxy acetone phosphate and gylceraldehyde-3-phosphate (GAP))
- GAP is converted to phosphoenol pyruvate using reduced NADH
- phosphoenol pyruvate is converted to pyruvate by pyruvate kinase using ADP to form ATP
what are the products formed in glycolysis?
- net of 2 ATP per glucose
- 2 NADH
- 2 pyruvate
what are the enzymes involved in glycolysis and how are they inhibited?
- hexokinase: converts glucose to G6P and inhibited by G6P
- phosphofructokinase: converts G6P to fructose-6-phosphate and inhibited by ATP
- pyruvate kinase: forms pyruvate from phosphoenol pyruvate and inhibited by ATP
which enzymes are present in the liver?
- glucokinase
- has a higher Km so requires higher [glucose] to be functional
- not inhibited by G6P
-liver is responsible for storing excess glucose so when [glucose] high, glucokinase increases rate of glycolysis
what types of respiration does glycolysis occur at?
aerobic and anaerobic
how are tumours and exercising muscles similar?
both generate ATP where there is very little oxygen
how do tumours respond to low oxygen?
-hypoxia induced factor (HIF1) senses low [O2] and stimulates transcription factors that express enzymes in the glycolytic pathway (hexokinase, PFK, glucose transporters)
why is glycolysis in the liver inhibited by citrate?
- liver uses glucose and glycolysis as a source of carbon skeletons
- high levels of citrate means there precursors of biosynthesis are abundant
what are the steps in the citric acid cycle?
- pyruvate (C3) is converted into acetyl CoA (2C) by pyruvate dehydrogenase, forming CO2 and NADH
- acetyl CoA (2C) is joined to oxaloacetate (4C) to form citric acid (6C) by citrate synthase
- citric acid (6C) is then converted to isocitrate (6C).
- isocitrate (6C) is then converted to α-ketoglutarate (5C) by isocitrate dehydrogenase, releasing a molecule of CO2 and NADH.
- α-ketoglutarate (5C) is converted to succinyl CoA (5C) by α-ketoglutarate dehydrogenase, releasing a molecule of CO2 and NADH.
- succinyl CoA (5C) is converted to succinate (4C), releasing GTP.
→-succinate (4C) is then converted to fumarate (4C), releasing FADH2.
-fumerate (4C) is converted to malate (4C).
→-malate (4C) is finally converted to oxaloacetate (4C), releasing NADH.
what does pyruvate dehydrogenase do and what is it stimulated and inhibited by?
- converts pyruvate to acetyl CoA
- stimulated by ADP and pyruvate
- inhibited by acetyl CoA, NADH, ATP
what does citrate synthase do and what is it inhibited by?
- joins oxaloacetate and acetyl CoA together
- inhibted by citrate
what does isocitrate dehydrogenase do and what is it stimulated and inhibited by?
- it converts Isocitrate to α-ketoglutarate
- it is stimulated by ADP
- inhibited by NADH and ATP
what does α ketoglutarate dehydrogenase do and what is it inhibited by?
- catalyses the conversion of α ketoglutarate to succinyl-CoA
- inhibited by NADH, ATP and succinyl-CoA
how many molecules of FADH2, NADH and GTP are produced per glucose molecule?
- FADH2 = 2
- NADH = 6
- GTP = 2
how is pyruvate dehydrogenase stimulated in muscles?
- stimulated by Ca2+
- causes increase in CoA production
how is [Ca2+] increased in liver?
adrenalin increases Ca2+ by activating α-drenergic receptors and IP3
what regulates pyruvate dehydrogenase in liver and adipose?
insulin
what is beri beri?
- a disease caused by deficiency in thiamine (fit B1)
- common where rice is staple food
- causes neurological and cardiac problems
- thiamine isa prosthetic group for pyruvates and α-ketoglutarate dehydrogenase
what is NADH and FADH2 used in?
OXPHOS
what happens to the H+ on FADH2 and NADH?
dropped off at the ETC to build up proton gradient
how is ATP generated in OXPHOS?
- H+ moves down proton gradient into the matrix of mitochondria
- creates proton motive force which provides energy for ATP synthase to phosphorylate ADP into ATP
how many molecules of ATP are produced from each NADH and FADH2?
- 1 NADH: 3ATP molecules
- 1 FADH2: 2ATP molecules
why do newborn babies need brown fat and where are they located?
- newborns cannot shover so the have brown fat
- brown fat have high [mitochondria] so provides alternative way to regulate heat
- located in shoulders and down the back
- as the babies grow, [brown fat] decreases
why are mitochondria in brown fat different to other mitochondria?
they express uncoupling proteins
what do uncoupling proteins do?
- they uncouple a generation of proton gradient from generation of ATP
- they get the H+ to take different route instead of going into the matrix which causes a generation of heat
what are OXPHOS diseases and what are the symptoms?
- common degenerative diseases
- caused by mutations in genes encoding for proteins in the ETC
- depending on the mutation, the symptoms may be evident near birth to early childhood
- metabolic consequence can be congenital lactic acidosis
symptoms:fatigue, epilepsy, dementia
