extremes of metabolism Flashcards
what are the two types of muscle fibres?
type 1 slow twitch
type 2 fast twitch
how to type 1 muscle fibres make energy?
oxidative metabolism from glucose
fatty acids in the longer term
what is an adaptation of type 1 slow twitch muscles?
lots of mitochondria
how do type 2 muscle fibres make energy?
glycolysis to make lactate
what is the main fuel of type 2 muscle fibres?
glycogen
what are the subtypes of type 2 muscle fibres?
A - contain myoglobin - aeorbic
B - anaerobic
what causes the balance of the type 2 muscle fibre subtypes to change?
levels of exercise
how much can ATP demand increase in exercise in skeletal muscle?
100x
what energy sources are used in exercise and in what order?
phosphocreatine –> muscle glycogen –> blood glucose/fatty acids
how do the levels of ATP, ADP and AMP change with the intensity of exercise?
as intensity increase
ATP decreases
ADP and AMP increase
what does AMP signal for during exercise?
increases glucose uptake in the short term and FA oxidation in the long term
what vitamin is needed for muscle contraction?
calcium
what activates phosphorylase kinase?
calcium bound to calmodulin
what does Pyruvate dehydrogenase complex do?
controls entry to TCA
what enzymes control pyruvate dehydrogenase complex and what effect do they have on it?
PDH kinase - inactivates PDC by phosphorylation in response to low NADH and ATP
PDH phosphatase - activates PDC in response to calcium
what enzymes are allosterically controlled by calcium?
alpha-ketoglutarate dehydrogenase
isocitrate dehydrogenase
how does AMP promote glycogen breakdown?
activates enzymes such as glycogen phosphorylase (when its not phosphorylated) and
phosphofructokinase-1
increases number of GLUT4 channels
what allosterically inhibits phosphofructokinase?
high levels of ATP
explain the mechanism in the heart to activate PFK1
PFK2 produces F-2,6-BP which is an allosteric activator of PFK1 - controlled by phosphorylation via AMP kinase
explain the structure of AMP dependent protein kinase
heterotrimeric
3 subunits - 2 regulatory and 1 catalytic
what is the function of AMPK?
sensor for energy status
Detects levels of AMP – when AMP is high, AMPK is activated –> increases no. of GLUT4
activating the carnitine shuttle
how does AMPK sense AMP levels?
specific domain on its gamma subunit
what controls AMPK?
phosphorylation on the Thr172 of the alpha subunit –> not dependent on AMP
how does AMPK activate the carnitine shuttle?
phosphorylates Acetyl-CoA carboxylase
stops acetyl-CoA from building up
malonyl-CoA is therefore made
inhibits CPT-1 which activates the carnitine shuttle
what happens to muscles in muscle fatigue?
running out of glycogen
depletion of phosphocreatine
excessive conversion of glycogen to glucose to lactic acid –> decreases pH and inhibits glycolysis
inefficient mitochondria
how does exercise affect the density of mitochondria
increases the density
what is ethanol metabolised to in the body?
acetyl-CoA
what are the 3 stages of alcohol metabolism in the body?
ethanol –> acetylaldehyde
Acetylaldehyde + NAD+ –> Acetate + NADH
ATP + Acetate + CoA –> AMP + PPi + Acetyl-CoA
in what ways can ethanol be converted to acetylaldehyde?
alcohol dehydrogenase - makes NADH
catalase - makes water
microsomal ethanol oxidising system - makes NADP and water
what is the function of Antabuse and how does it work?
inhibits acetaldehyde dehydrogenase so you get more acetylaldehyde. Makes you feel sick sooner when you start drinking –> stops you from drinking alcohol.
what is another name for Antabuse?
disulfiram
what are the biochemical effects of alcohol on the body?
High levels of Acetyl-CoA = excess FA synthesis and excess ketone bodies
high levels of NADH = inhibition of the TCA cycle. =more pyruvate is converted to lactate as NAD+ needs to be regenerated –> lactic acidosis
why does the immune system have a variable energy demand?
needed to produce ROS to kill microbes
energy to make antibodies
energy is required in phagocytosis
why does the immune system require NADPH?
to make ROS
how is NADPH needed by the immune system made?
from the pentose phosphate pathway
converting malate to pyruvate in the cytoplasm
what is the Warburg effect?
regardless of how much O2, cancer cells have major up regulation of glycolysis (due to mutations of Hif protein)
why do cancer cells have increased use of amino acids?
to feed into the TCA cycle to increase energy production
