Energy Flashcards
Why do we eat?
Need energy for metabolism:
- synthesis of new molecules
- establishing ion gradients
- mechanical work
- keeping warm
Define catabolism?
breakdown of complex molecules to release energy or carry out mechanical work
Define anabolism?
synthesis of new molecules from less complex components
Why study metabolism?
- Metabolic basis of disease eg diabetes, atherosclerosis, gall stones
- Diseased state changes way body uses food eg cancer
- To understand disease need to know how body normally deals with nutrients
- Can use changes in metabolites to aid diagnosis + to follow treatment
What diff types of metabolic pathways require?
rapid generation (secs) eg exercise longer (minutes, hours) involving storing molecules (can take months/days)
Describe energy provision
- ATP is central to a cell so bodies energy provision
- ATP acts as both an acceptor + donator of energy
- Short term reservoir of energy
How much ATP do we need?
- Total energy available from hydrolysis of ATP = 65kj/mole
- For rest = 40Kg/24hour
- For exercise = 0.5Kg/minute
How much ATP does the body have?
100g
How does body meet demands for energy?
re-synthesise ATP from ADP via oxidative phosphorylation in mitochondria
Major oxidative pathways?
Glycolysis
Citric acid cycle
Electron transport coupled to oxidative phosphorylation
FA oxidation
Describe glycolysis
-6C glucose -> 2x 3C pyruvate
-glucose phosphorylated (consuming energy) -> G6P
-maintains conc gradient across membrane
-G6P undergoes conformational change -> fructose-6-phosphate
-fructose-6-phosphate phosphorylated -> fructose 1,6
bisphosphate (C6)
-F6BP -> 2x 3C
-each C :
NAD+ -> NADH
ADP -> ATP
phosphoenol pyruvate -> pyruvate
ATP synthesised again
Balance sheet for glycolysis?
Reactants : 1 Glucose 2 NAD+ 2 ADP 2 Pi Products : 2 Pyruvate 2 NADH 2 ATP
What regulates glycolysis?
Enzymes catalysing irreversible reactions regulated by:
-reversible binding of allosteric effectors
-covalent modification eg phosporylation
-transcription
Measured in terms of ms, s, hrs
Role of hexokinase?
glucose -> G6P
What’s hexokinase under control by?
product G6P so negative feedback
Role of pyruvate kinase?
phosphoenol pyruvate -> pyruvate (with release of ATP)
What’s pyruvate kinase under control by?
product ATP so negative feedback
Role of phosphofructokinase?
fructose-6-phosphate -> fructose 1,6 bisphosphate
What’s phosphofructokinase under control by?
product ATP, citrate, H+ negative feedback
AMP (product of ATP -> ADP, which gives an indication of energy levels of the cell) positive feedback
Effect of inhibiting phosphofructokinase?
-build-up of G6P inhibiting hexokinase
-in liver, we have hexokinase + glucokinase which is not
affected by G6P build up
-glucokinase has a lower affinity for glucose so is
active at higher conc of glucose
How to make AMP?
ADP + ADP -> ATP + AMP via adenylate cyclase
Role of AMP?
ATP made from 2ADP via adenylate kinase gives ATP + AMP so AMP is a better indicator of energy state
How is phosphofructokinase inhibited?
high conc of ATP by lowering the affinity for fructose 6 phosphate, citrate, low pH
How regulation of glycolysis in liver reflects its diverse functions?
-Liver has more functions than muscle so regulation of glycolysis more complex
-High conc of ATP inhibit PFK
-Citrate inhibit PFK as indicates precursors of
biosynthesis are abundant
-Low pH in liver irrelevant as liver doesn’t produce lactate
-PFK stimulated indirectly by build-up of F6P.
-Hexokinase inhibited by G6P but liver also has glucokinase which isn’t inhibited by G6P (glucokinase only activated when high glucose)
-Indirect activation by F6P -> F26bisP when high glucose is feed forward regulation
Role of glucokinase?
activated when high glucose in liver not inhibited by G6P
Function of glycolysis?
- Degrades glucose to generate ATP
- Provides building blocks for synthesis of cellular components
Why’s rate of conversion of glucose to pyruvate regulated?
- 3 non-reversible steps phosphofructokinase inhibited by ATP + citrate, activated by AMP + fructose 2-6 bisphosphate
- In liver bisphosphate signals glucose is abundant. PFK active when either energy or building blocks needed.
- hexokinase inhibited by G6P
- ATP + alanine inhibit PK
- PK activity max when energy charge is low + glycolytic intermediates accumulate
What do exercising muscles and tumours have in common?
Their energy needs are met through anaerobic respiration
Why do tumours use glycolysis?
- tumours outgrow their blood supply
- O2 reduced
- activation of transcription factor HIF-1α
- HIF-1α regulates expression of enzymes in glycolytic pathway
Why’s lactate produced?
-C3 undergo es areaction where NAD+ -> NADH -enables ATP to be produced -to allow reaction to continue, pyruvate -> lactate -NADH -> NAD+ -NAD+ fed back to earlier reaction -enables more molecules to flow through this part of glycolysis -replenish NAD+ -but muscle can’t cope with lactate -lactate exported via blood to liver
Summary of energy I?
-Glycolysis is 6C glucose ->2x 3C pyruvate
-1st part of glycolysis consumes energy
-2nd part generates 2NADH + 2ATP
-ATP used as direct source of energy
-NADH used to generate energy via oxidative phosphorylation (which needs O2 to occur)
-In muscle O2 delivered insufficient so 3C pyruvate -> lactate allowing 2nd part of glycolysis to occur as replacing the NAD+
-Tumours use glycolysis as they grow faster than a blood supply can form around it so insufficient O2
-In a liver cell or less active muscle, pyruvate -> Acetyl
CoA which fed into the Krebs cycle
What does aerobic respiration require?
Requires O2,citric acid cycle, oxidative phosphorylation.
Where does aerobic respiration occur?
mitochondria
Where does TCA cycle occur?
matrix
Where does oxidative phosphorylation occur?
inner mitochondrial membrane
Product of TCA cycle?
for each glucose: 6NADH (+2 from before) 2FADH 2GTP 4CO2 (+2 from before)
Describe citric cycle
-in presence of O2
-pyruvate -> ACoA (2C) + enters citric acid cycle
-ACoA + oxaloacetic acid (4C) -> citrate (6C)
-citrate undergoes series of reactions –> loss of 2CO2
3 NADH + 1 FADH2 formed per cycle
1 GTP molecule is formed
ATP not produced in citric acid cycle
Key facts about citric acid cycle?
- Krebs cycle provides electrons for mitochondrial oxidative phosphorylation
- Integrates carbohydrate, lipid, protein metabolism
- Aerobic
- Oxidizes ACoA to generate NADH H, FADH2, CO2
Role of Kreb’s cycle?
- Oxidation (electron harvesting) producing NADH, FADH2 which become substrates for electron transport chain
- Source of building blocks for vital bio-molecules
What regulates entry into citric acid cycle?
- formation of ACoA from pyruvate is irreversible via pyruvate dehydrogenase
- this commits glucose C skeleton to either oxidation to CO2 + energy production or FA synthesis
Role of pyruvate dehydrogenase?
pyruvate -> ACoA
What’s pyruvate dehydrogenase regulated by?
- Inhibited by products NADH + ACoA
- Regulated by phosphorylation by a kinase + phosphatase (covalent modification)
What regulates entry into the citric acid cycle?
- In muscle pyruvate dehydrogenase activated again via phosphatase – stimulated by Ca2+
- In liver adrenalin increases Ca2+ via activation of a adrenergic receptors + IP3
- In liver + adipose tissue, insulin stimulates phosphatase which funnels glucose to FA synthesis
Sig of build up of NADH + ACoA?
inform enzyme that energy needs of cell are meet or FA are broken down to produce NADH + ACoA - sparing glucose.
Control points of citric acid cycle?
-ACoA -> citrate via citrate synthase
-Isocitrate -> α-ketogluterate via isocitrate dehydrogenase
-α-ketogluterate -> succinyl CoA via α-ketogluterate
dehydrogenase
Role of citric synthase?
ACoA -> citrate
What inhibits citric synthase?
product citrate so when enough ATP, ACoA directed to other ways eg FA synthesis (if you can’t use it store
it)
Role of isocitrate dehydrogenase?
Isocitrate -> α-ketogluterate
What regulates isocitrate dehydrogenase?
inhibited by NADH, ATP + stimulated by ADP
Role of α-ketogluterate dehydrogenase?
α-ketogluterate -> succinyl CoA
What regulates α-ketogluterate dehydrogenase?
inhibited by NADH, ATP, Succinyl CoA.
(note that the control of entry into TCA spoken of earlier (pyruvate -> ACoA) is inhibited by NADH, ATP, ACoA. It is stimulated by ADP and pyruvate)
Effect of inhibiting isocitrate dehydrogenase +
α-ketogluterate dehydrogense?
- build up of citrate
- citrate transported out of mitochondria
- where it inhibits PFK
- stops glycolysis
- citrate also act as a source of ACoA for FA synthesis
Describe what Beriberi is?
- Def in thiamine (Vit B1)
- Common where rice common
- Characterised by cardiac + neurological symptoms
- Thiamine is a prosthetic group for pyruvate + α-ketogluterate dehydrogense
- Neurological disorders common as glucose is primary source of energy
Fate of NADH + FADH2?
-electron transport coupled to ATP synthesis
-needs 3H+ to make 1ATP
-1H+ used to transport ATP out of matrix so 4H+
generates 1ATP
-ETC removes hydrogen from oxidisable substrates : NADH + FADH2 .
-hydrogen enter ETC
-hydrogen -> elctron + H+
-electron passed via series of cytochromes going from high to low energy state powering proton pumps
-proton + O2 -> water
-proton pumped across inner mitochondrial membrane into IMS
-generates pH gradient transmembrane potential (proton motive force)
-membrane act as a barrier to reestablishment of gradient
-gradient harnessed to produce ATP
How many protons generate ATP?
-needs 3H+ to make 1ATP
-1H+ used to transport ATP out of matrix so 4H+
generates 1ATP
How much ATP produced from NADH + FADH2?
-each NADH produces 3ATP
-each FADH2 produces 2ATP
(these are approximations, not always 100% efficient)
How many protons pumped out for each NADH + FADH2?
10H+ pumped out for every NADH
6H+ pumped out for every FADH2
Describe ATP synthesis
- ATP synthase is transmembrane protein
- acts as motor
- H+ pumped out into IMS will be able to drop back down their pH gradient via ATP synthase
- generates ATP from ADP
How neonates generate heat?
proton movement across inner mitochondrial membrane no longer coupled with ATP synthesis.
- neonates cannot shiver so no heat
- lose heat from their surface
- possess brown fat around neck + shoulders
- brown fat has many mitochondria
- brown from cytochromes which has iron in structure
- baby mitochondria has uncoupling protein
- uncouples proton gradient with ATP synthesis
- uncoupling protein is an alternative route where H+ moves down its conc gradient
- so it doesn’t generate ATP but heat!
Describe OXPHOS diseases?
- Common degenerative diseases
- Caused by mutations in genes encoding proteins of ETC
- Symptoms : fatigue, epilepsy, dementia
- Dependent on the mutation, symptoms near birth to early adulthood
- Metabolic consequence can be congenital lactic acidosis
What regulates ETC?
- Governed by need for ATP
- Electron transport coupled to phosphorylation : ADP to ATP
- EXCEPTION : regulated uncoupling leads to the generation of heat
