meds2003 ver.ka Flashcards
1
Q
How does muscle contraction use ATP
A
actin and myosin interaction
The faster the contraction, the faster the use of ATP
2
Q
How is muscle using ATP at rest?
A
maintaining ion gradients, sacroplasmic reticulum and calcium
3
Q
Outline the features of type1-red muscle
A
contracts relatively slowly
many mitochondria good blood supply
4
Q
outline the features of type 2b white muscle
A
contracts relatively rapidly
few mitochondria
poor blood supply
full of contractile filaments
5
Q
What limits ATP production
A
The hydrogen/electron carriers are in short supply
the ADP are in short supply
6
Q
What is an essential feature of the inner mitochondrial membrane to create a proton gradient
A
The inner mitochondrial membrane is impermeable to protons
7
Q
How is proton pumps controlled?
A
proton gradient.
Moreover, the proton pumps only flow into the matrix if the ATP is being made, which is how it is coupled.
With no proton pumping there is no hydrogen/electron movement down the electron transport chain
8
Q
Why is there a need for coupling
A
ATP stores are pathetic
9
Q
Why is Fatty acids a good energy source
A
Fatty acids are very reduced, so they have a large number of hydrogen
10
Q
How are fatty acids stored
A
They are stored as triglyceride, which makes them very energy dense, hydrophobic and huge stores build up
11
Q
what tissues could glycogen be used in
A
all tissues
12
Q
some facts about glycogen stores
A
hydrophilic, lots of water associated
low stores (about 300g)
inefficient; 16kJ/g
13
Q
some general facts about glycolysis
A
happens in all tissues wholly cytosolic have no requirement for oxygen it happens very very fast it is very very inefficient ATP generation almost irrelevant
14
Q
What is the most readily available fuel in gentle exercise
A
glucose.
Glucose transporters move to cell surface
15
Q
What happens hormonally when we engage in gentle exercise
A
A tiny decrease in blood glucose gives big hormonal responses,
insulin down and glucagon up.
We need this level of control to maintain 5mM of glucose for our brains
16
Q
What is the effect of low insulin and high glucagon
A
It stimulates glycogen breakdown in the liver and a stimulation of fat breakdown in white adipose tissue
17
Q
Why do we need to engage in glucose recycling
A
because glucose stores are limited. We need to try substitute glucose where we can
18
Q
What happens several minutes after gentle exercise
A
fatty acids take over from insulin decrease and glucagon increase.
Glucose is still taken into the muscles
and lactate goes to the liver for the resynthesis of glucose for gluconeogenesis
19
Q
What happens in moderate exercise
A
the rate of fatty acid utilisation increases but the enzymes that catalyse fatty acid oxidation soon reach their maximum capacity
And the inhibition of glucose oxidation is removed to get some energy from glucose
glucose oxidation occurs
less glucose recycling and liver glycogen stores are depleted faster
20
Q
Where does the glucose come from in moderate exercise
A
the glucose comes from the liver
21
Q
What happens when we undergo strenuous exercise
A
muscle glycogen is now broken down
and glycolysis is happening
so we are also forming lactate
22
Q
Why is glycogen important
A
Because once glycogen has run out, only fatty acid oxidation can be used for ATP generation. And we cannot sprint if there is no glycogen
23
Q
What happens during sprinting
A
We use type IIb muscles
24
Q
Why can’t we use fatty acids during sprinting
A
type iib muscles have poor oxygen supply and low mitochondria
25
Why can't we use blood glucose
type iib muscles used
| There would be a delay in transporter recruitment and poor fuel supply
26
What is the glycolysis happening in the muscle
glycogen=>g6p=>pyruvate=>lactate
27
creatine phosphate
creatine phosphate is an instant store of ATP,
creatine phosphate+ADP=> ATP+ creatine
28
What does NAD oxidise
oxidises CH2CHOH
29
What does FAD oxidise
it oxidises CH2CH2 to CHCH
30
how is fatty acid travelling in the blood
bound to serum albumin
31
How is fatty acid bound in the cytoplasm
fatty acid binding protein
32
What traps Fatty acid
CoA
FA+CoA=> Fatty acyl CoA with the help of ATP and fatty acyl synthase
33
What is CoA
A large polar molecule with an important thiol group
pantothenic acid and
3' phosphoadenosine diphosphate
34
How is fatty acid travelling into the mitochondria
fatty acyl CoA too polar, and too large,
so carnitine acyl transferase 1 removes CoA, and carnitine reacts with fatty acid to form fatty acid carnitine.
Fatty acid Carnitine can then react with CoA to form fatty acid CoA with CAT2, and then the carnitine goes back to the cytoplasm
35
outline what is the first hydrogen/electron stripping step of fatty acid
involves FAD to form a c=c double bond
| eventually the c=c double bond is hydrated to form an OH group
36
Second hydrogen/electron stripping step
inolves AND
| which then forms a C=0 group that is then attacked by CoA
37
Each time beta oxidation takes place, the fatty acid part loses an...
acetate chunk
38
Where is GLUT1 found
in all cells all the time
39
Where is GLUT4 found
in muscle and adipose tissue
40
Where is GLUT 2 found
in liver and pancreas
41
What happens in early glycolysis
glucose 6 phosphate turns into fructose 6 phosphate which is then phosphorylated using ATP with phosphofructokinase to give fructose 1, 6 bisphosphate, which splits off to give two 3 carbon molecules
42
What happens in the Return phase
g3p ix oxidised with NAD, and a phosphate is added, this 2 phosphate molecule is what causes substrate level phosphorylation, when it reacts with ADP
43
What is the yield of glycolysis
2ATP per glucose 2 pyruvate and 2 NADH
44
What is the substrate of the krebs cycle
Acetyl CoA
45
Where does the krebs cycle take place
in the mitochondria
46
What is the overall strategy of the krebs cycle
completely oxidize acetate carbons to CO2
produce lots of NADH, FADH2 and an ATP
regenerate carrier
47
What happens when we have no proton gradient (uncoupling)
No back pressure to stop protons from pumping
No restriction on hydrogen/electron movement down the lectron transport chain to oxygen
Instant regeneration of NAD from NADH
massive fuel oxidation rate
massive oxygen consumption
no ATP synthesis
48
What is an example of a natural uncoupling
UCP1
49
How does UCP1 work
basically it's function is to generate heat
Noradrenaline binds to a beta 3 receptor which stimulates fatty acid release, and opens the proton channel to allow protons to pass through
50
How are the proteins arranged in the electron transport chain for H+ expelling and H+ consuming reactions
h+ expelling reactions are on the outside
| H+ consuming reactions are on the matrix side
51
approximately how many protons are pumped out for each NADH
about 10
52
What are 3 interesting features of NAD
it is reoxidised by complex 1
it likes to rip H/e off from CH-OH groups to convert them to C=O groups
it is a dinucleotide-2 nucleotides joined back to back
the nicotanamide group is derived from nicotinic acid
53
FAD 3 interesting features
present in complex II
likes to rup H from a saturated hydrogen carbon chain
it is totally stuck in complex II
54
what are 5 interesting features about UQ
UQ is very hydrogphobic
they also pick up hydrogens from complex II
reduced UQ is UQH2
UQH@ transfers hydrogens to complex III
55
What is the function of cytochrome C and iron
Cytochorme C picks up electrons from complex III and gives the electrons to complex IV
They have a prosthetic group which changes from ferrous to ferric
56
how do you get NADH to the ETC
glycerol 3 phosphate shuttle
| Malate Aspartate Shuttle
57
What is the quirk of the G3P shuttle
it bypasses complex I
58
outline what happens in the Glycerol 3 phosphate shuttle
dihydroxyacetone phosphate protonated by NADH and cytoplasmic glycerol 3 phosphate dehydrogenase then goes to glycerol 3 phosphate.
Glycerol 3 phosphate hydrogens protonate E- FAD which creates a cycle
59
malate aspartate shuttle
too hard to describe
60
What are the 4 routes to Q
from complex 1
from complex 2
from its first step of beta oxidation
from the glycerol 3 p shuttle
61
How does the skunk cabbage uncouple the reactions
?
62
What are the dangers of free radicals
electrons in the UQ pool can react with molecular oxygen to produce free radicals
and this can cause mutations to DNA
The free radicals then move to complex IIi
63
How is ATP made from 2 ADP
with adenylate kinase
translates a small change in ATP to a relative large change in AMp
64
Relative ATP concentration before ATP depletion
About 5.0mM
65
relative ATP concentration after ATP depletion
4.5mM
66
relative ADP concentration before ATP depletion
1.0mM
67
Relative ADP concentration after ATP depletion
1.0mM
68
Relative AMP concentration before ATP depletion
0.1mM
69
Relative AMP concentration after ATP depletion
0.6mM
70
properties of the rate limiting step
irreversible
1) need alternative enzymes to go back
2) not equilibrium under physiological conditions
3) committed steps
Saturated with substrate
1) low Km or [S]>>Km
2) working at Vmax
71
What are the 3 main ways to change the rate/flux of the metabolic pathways
1) make the rate limiting enzyme go faster/slower
2) turn the rate limiting enzyme on/off or make it work the other way
3) increase the rate of transcription/translation of the rate limiting step or change its rate of degradation
72
Give an example of allostery in the regulation of the metabolic pathway
PFK,
it does not like a high concentration of its substrate ATP.
it has binding sites for AMP away from the active site
Binding AMP changes the way that PFK responds to ATP
PFK also binds citrate allosterically
Citrate inhibits PF when citrate concentrations are high.
73
Give an example of feedback inhibition in the regulation of the metabolic pathway
The initial glucose trapping reaction.
Hexokinase
Inhibition by the product G6P prevents excessive trapping, so if G6P is not used, glucose is not trapped.
74
Give an example of covalent modification in the regulation of the metabolic pathway
PDH
PDH kinase, PDH phosphatase,
acetyl CoA
insulin
75
amphiphilic molecules can act as
detergents to emulsify fat into tiny particles/ micelles
76
What are bile salts made from
made from cholesterol in the liver.
| It is the addition of polar groups
77
Where is Bile Salts secreted and stored
stored in the gall bladder, and released towards the small intestine
78
What happens to bile after the digestion of fat
It is reabsorbed and taken back into the liver via the hepatic portal vein
79
Why is the production of bile salts important from a metabolism standpoint
production of bile salts is the only way in which cholesterol is metabolised and disposed
80
how are fat contained
fat is contained in the core of micelles formed by bile salts.
Chyme, emulsion, and easy for lipase to interact with
81
What is the function of pancreatic lipase
it hydrolyses fat into fatty acid and glycerol plus a mixture of mono and diacyl glycerols
82
Where are pancreatic lipase found
everywhere
83
What is the function of apoproteins
They act as enzymes and help with docking
84
Where are chylomicrons made
in the intestinal cells from the gut, and released into the lymphatic system
85
packaging of cholesterol
Where exactly does this fit. Cholesterol is transformed into cholesteryl ester from acyl coa cholesterol acyl transferase.
This forms the core of a lipoprotein.
86
What do chylomicrons do?
They interact with lipoprotein lipase (LPL) on the surface of cells and capillaries
The fat is hydrolysed into fatty acids and glycerol, and then taken up for storage or oxidation.
Apparently you could re-esterfy it with glycerol 3 phosphate
87
What happens with the chylomicrons as it passes through the capillary
Fat is removed from chylomicrons
88
What happens to chylomicrons in the end
They get endocytosed in the liver. There is still quite a bit of fat remaining in the liver
89
What is the liver's function in fat import and export
The liver assembles very low density lipoproteins from fat and cholesterol esters
The fat could also be made by lipogenesis. The VLDL is then excreted into the blood stream.
90
What happens when VLDL is in the blood
LPL in the peripheral tissues works in peripheral tissues on VLDL, depleting the fat and creating low density lipoprotein
91
What is the function of LDL
Tissues take up LDL through the LDL receptor
| This is how cholesterol is delivered to the tissues
92
How do cells create their own cholesterol
HMG-CoA reductase basically turns acetate into choletserol.
93
What is HMG-CoA reductase regulated by
It is regulated by insulin, cholesterol levels, gene expression, enzyme degradation and even a circadian rhythm
94
Why is elevated blood LDL bad
LDL particles become oxidised with time.
Macrophages take up ox-LDL without control-becoming foam cells
This creates an inflammatory environment that encourages the formation of plaques
95
What is the function of HDL
They basically get a cargo of cholesterol, and then bring it to the liver. It happens when the cells want to get rid of cholesterol.
96
What does CETP do
They catalyse the exchange of cholesterol ester for triglyceride.
They could apparently interact with a VLDL or a chylomicron when doing this
97
What are the consequences of having CETP
HDL takes back more fat and less cholesterol
Cholesterol remains in circulation
VLDL enriched with cholesterol
98
What are functions of insulin
Insulin stimulates glucose uptake in the GLUT-4s in the muscle and adipose tissue and the conversion to storage products.
Therefore it can cause increased oxidation
99
Difference between intolerant and diabetic
Intolerant has normal fasting glucose, but sluggish clearance.
Diabetic has fasting hyperglycemia. Relentless exposure to high concentration of glucose
100
What are consequences of amylose being a linear structure
it can form helices that are difficult for amylases to penetrate. And because it is difficult to penetrate, there is sometimes flatulence, because the amylose has stayed in the body too long.
101
What does the glycemic index describe?
The post prandial glucose response.
102
What is the test food and reference food
Reference food is normally 50 g glucose
| the test food is usually an amount that will give 50 g of digestible carbohydrate.
103
What is the average GI of modern grains
over 80
104
What is the average GI of legumes
under 30.
105
What time periods matter when thinking about GI
over 1 hr 30 minutes is what matters
106
Should GI apply to non starches?
Sugary foods or low GI because half the carbohydrates are fructose. Similarly, fructose containing foods are low GI
Somtimes galactose is used in our dairy food
107
Outline how glycogen is synthesised
glucose 6 phosphate is turned into glucose 1 phosphate and then glucose 1 phosphate is turned into UDP glucose after using UTP to release PP. The UDP glucose then reacts with glycogen and basically elongates the glycogen. The synthesis is from C1 through to C4
108
How does glycogen synthase work?
Basically UDP glucose has its UDP removed, and then the 1' carbon forms a glycolytic bond between 1' and 4'
109
What enzyme causes branching?
Glycogen branching enzyme
110
What is glycogen synthase regulated by
It is regulated by reversible phosphorylation
| It is active when dephosphorylated
111
What enzyme does insulin stimulate which also has an effect on glycogen synthase
insulin could stimulate protein phosphatase 1, also known as PPI. This causes GS to be dephosphorylated and active, so Insulin could activate GS
112
What is the function of phosphofructokinase
It is the rate limiting step of glycolysis
113
So what is phosphofructokinase regulated by
it is regulated allosterically by AMP, and low energy charge
114
how does insulin indirectly activate PFK
insulin stimulates GS, Glycogenesis is anabolic, and therefore requires ATP. This drops and increases ADP and AMP. PFK is regulated allosterically by AMP and therefore this signals to store fuels to be burnt
115
Glucokinase properties
rapidly converts glucose to G6P. It is not inhibited by the build up of G6P. High Km for glucose is not saturated by high levels of liver glucose so G6P rapidly increases as blood glucose rises
116
What is the effect of G6P on inactive glycogen synthase
it could phosphorylate GS and it also stimulates the dephosphorylation of GS
117
What is the difference between glycogenolysis in the liver and in the muscle
in the liver, there is a "push" mechanism where glycogenesis responds to blood glucose without the need of insulin. Although insulin will stimulate glycogen synthase further
In muscle G6P never gets high enough to stimulate GS.
The push method does not happen in muscle
It is more of a pull as insulin stimulates GS and drags glucose into glycogen
118
what is the difference between glucokinase and hexokinase?
glucokinase only works on glucose, it has a high Km for glucose
It is not inhibited by G6P
only presents in liver, beta cells
responsive to changes in glucose blood
Hexokinase works on any 6C sugar, low as fuck Km. It is strongly inhibited by its product G6p. Present in all tissues. Easily saturated.
