Krebs and OP Flashcards
what are the energy stores and requirements for a 70kg male
triglyceride (fat) 400MJ usable protein 100 MJ liver glycogen 2.4 MJ blood glucose 0.16 MJ daily needs - 12
what is the average concentration of ATP in cells
6mM
what is the turnover of ATP and how much does the average human body contain
75g of ATP at any one time but the turn over is 75kg/day
how much of ATP is produced in the mitochondria
95% under aerobic conditions
what is the difference between the inner and outer membrane of the mitochondria
outer: smooth and freely permeable to molecules under 5000 Da, no ionic or electrical gradients
inner: folded into chirstae, permeable to a small number of molecules only via specific transporters
very good electrical insulator, capable of minting large iconic and electrical gradients
contains more protein than lipid, respiratory enzymes transporter proteins
what is the role of pyruvate dehydrogenase (PDH) and where does it act
pyruvate travels from cytosol to mitochondrial matrix where the enzyme converts it to acetyl CoA
what does the dysfunction of PDH cause and what is it due to
caused by lack of thiamine which leads to beriberi - neurological and cardiovascular symptoms
what is wsernickes-korsakoff syndrome
lack of thiamine seen in alcohol addicts
what is the “key decision point” of PDH
Acetyl CoA cannot be converted back to glucose and there commits those C atoms from glucose for energy production
what are the two stages of the kerbs cycle
synthesis of 6-C compound citrate which then loses 2 C as Co2 to become 4-C compound succinyl CoA
oxidation of the 4-C compound to reiterate oxaloacetate and initiate another round of cycle
what are the main outputs of the krebs cycle
reduced co-enzymes NADH and FADH2 - electron carriers
CO2
how is the krebs cycle controlled
entry of pyruvate via need for energy
availability of A CoA from fat oxidation
need for energy monitored by ATP:ADP ratio and NADh:NAD+ ratio
what are the three key enzymes of the krebs cycle
citrate synthase
isocitrate dehydrogenase
a-ketoglutartae dehydrogenase
why do type 1 diabetes patients synthesise ketones
diabetic patients can’t use glucose due to absence of insulin
inhibits glycolysis and low pyruvate
fatty acids are mobilised from adipose tissue and oxidised to acetyl CoA - lack of oxaloacetate prevents A CoA entering krebs and ketones are made instead
what are the two processes within the electron transport chain
electron transport - energy of electrons in NADH and FADH2 is used to create a proton gradient across the inner mitochondrial membrane - oxidation
ATP - synthesis - energy from the proton gradient is used to phosphorylate ADP to synthesise ATP - phosphorylation
where does oxidative phosphorylation occur
across inner mitochondrial membrane
what are all the components of the OP system
complex 1-4 ubiquinone (between 2 and 3) cytochrome C (between 3 and 4) f0f1 ATPase adenine nucleotide transporter Pi transporter
where do these molecules enter the transport chain
NADH
FADH2
O+2H+
complex 1
complex 2
complex 4
how does cyanide affect the ETC
blocks complex 4 and formation of water
what is released between each complex and which complex does the most
movement of molecules releases energy
biggest change is complex 3 to complex 4
how many protons are pumped into the mitochondrial inter membrane space from each pair of electrons from NADH
10
which molecule allows movement of electrons back from the inter membrane space into the mitochondrial matrix
F0F1 ATPase down the proton gradient
what happens when protons move through the F0 portion in the membrane
causes it to rotate the stem inside the F1
what is required for the formation of ATP from other transporters in the membrane
ADP which comes in with H+ and Pi
how many protons are required to make 1 ATP
4
what happens to NADH in the cytosol vs in the matrix as it cannot pass the inner membrane
oxidised in the cytosol and reduced in the matrix
what type of compound can uncouple oxidation from phosphorylation
weak acids soluble in the membrane - they then associate with protons which dissipates the proton gradient
can electric transport occur without ATP synthesis
yes
what is the reason for uncoupling
creates non-shivering heat in newborns
how does uncoupling cause thermogenesis
contains brown adipose tissue which has thermogenin (uncoupling protein 1)
when temp drops SNS releases NA which increased free fatty acids in cytosol which activates thermogenin
as ET is uncoupled from ATP synthesis energy is rebased as heat instead
what molecule is used to identify BAT in adults
18-fluorodeoxyglucose
what causes levels of BAT to decrease
age and obesity
what can be used as a therapeutic target to promote triglyceride clearance and weight loss
beige adipose tissue which can switch between brown and white forms
what is Dinitrophenol
“weight loss product”
(1930’s)
side effects caused hyperthermia, tachycardia, excess sweating, blindness (cataracts) and withdrawn symptoms
