Extremes of metabolism Flashcards
Name the two types of muscle fibers
Type 1- slow twitch
Type 2- Fast twitch
Describe the properties of slow twitch muscle fibers
Short term energy supply- Oxidative metabolism from glucose
Long term energy supply- Fatty acids
Rich in mitochondria
Describe the properties of fast twitch muscle fibers
Short term- anerobic metabolism- (glycolysis to lactate)
Main fuel glycogen
Long term- Main fuel blood is glucose
What are the subtypes of fast twitch muscles? What is the difference between the two?
2 subtypes
A- contains myoglobin (aerobic)
B- anaerobic
Can the properties of the muscles fibers change? If so how?
Yes, depending on the type of exercise/ training
During exercise where do you muscles seek energy?
Blood glucose
Glycogen
Fatty acids
Phosphocreatine
What is the use of AMP during exercise?
It increases during exercise
This stimulates increased glucose uptake short term and fatty acid oxidation long term
How does calcium cause increased muscle contraction?
Phosphorylase kinase (CAMKinase) a is activated by a calcium subunit calmodulin. Phosphorylase kinase then breaks down glycogen to produce glucose
More calcium= more muscle contraction
What is the name of the calcium sub unit responsible for muscle contractions
Calmodulin
What is the purpose of pyruvate dehydrogenase complex?
Controls the entry to the TCA cycle
How is pyruvate dehydrogenase complex regulated?
It is controlled by the phosphorylation of PDH kinase in response ATP and NADH levels.
PDH phosphotase is activated by calcium. It reverses the effects of PDH kinase on PDC (keeping it active).
PDC is allosterically activated by low NADH and ATP and high ADP and NAD concentrations
Which enzymes in the TCA cycle are controlled by calcium? What else controls these enzymes?
Isocitrate dehydrogenase and
alpha-ketoglutarate dehydrogenase
NAD levels also controls the enzymes
Maintaining high ATP production
How does AMP regulate metabolic activity during exercise
During excerise ATP is low and AMP increases.
AMP allosterically activates glycogen phosphorylase (when not phosphorylated)
This promotes glycogen break down providing more fuel.
It in general allosterically activates enzymes (PFK-1) at the start of glycolysis and glycogenolysis.
Increase GLUT4 membrane channels so more glucose uptake
What is the structure of AMP kinase?
Which part of the structure senses energy status?
3 subunits- alpha, beta, gamma
2 regulatory
1 catalytic
Gamma subunit
How is AMP kinase controlled?
Phosphorylation on the Thr172 on alpha subunit
Name one effect of AMP Kinase. Which other molecule does the same thing?
Promotes movement of GLUT4 to the membrane of muscle cells
Insulin does the same
What is the difference between phosphofructokinase1 and phosphofructokinase2
1- tissues
2- heart
How is phosphofructokinase1 regulated?
Allosterically inhibited by high levels of ATP
Activated by ADP and AMP
How is phosphofructokinase2 regulated?
Firstly it produces F-2,6-BP from F6P. This is allosterically activated by PFK1 and controlled by phosphorylation using AMP kinase
Which molecule mediates the transition from glucose to fatty acid metabolism during prolonged exercise? How does it do this?
AMP kinase mediates this transition.
It phosphorylates acetyle-CoA carboxylase
making it inactive. This stops the production of malonyl coA which inhibits carnintine shuttle
This activates the carnintine shuttle which transports fatty acids into the mitochondria for break down to make ATP
During long periods of exercise what happens to the PH and what effect does this have on other metabolic processes?
Production of lactic acid decreases PH. This inhibits glycolysis and oxidative phosphorylation
What happens when you run out of energy?
1st: run out of phosphocreatine
2nd: run out of glycogen (700g of glycogen need for a marathon; body only has 500g in storage – 400g in muscle + 100g in liver)
3rd: Over-reliance on FA metabolism for energy: lipolysis has a max energy output of 60% so might not meet the energy needs
FA oxidation is slower, requires more oxygen than glycolysis and TCA
4th: lactic acid build up decreases the pH in muscles and slows glycolysis and oxidative phosphorylation
What happens to mitochondria as you age? What else decreases your levels of mitochondria?
It decreases with age
It decreases with inactivity
What are the steps of metabolic changes during starvation?
- Glucose levels fall; insulin goes down, glucagon goes up
- Glycogen break down begins and can sustain body for about 30 hours
- Switch to FA break down which can sustain body for 2-3 days
- After 2 days gluconeogenesis and production of ketone bodies becomes only source of glucose & energy.
- Last resort for glucose is breakdown of protein (muscle) to release amino acids for gluconeogenesis
How is alcohol metabolised?
in liver- 3 ways
Most common- methanol—-> acetaldehyde (toxic) using alcohol-dehydrogenase
What causes hangovers?
Acetaldehyde produced from methanol
Which drug is used to treat alcoholics? How does it work?
Disulrifam (anatabuse)
ALDH2 activity
Which ethnic groups is predisposed to having hang overs? Why is this?
People of Asian
- deficiency of acetaldehyde dehydrogenase (ALDH2) enzyme due to the rs671 polymorphism is 30-50% of pop.
What are the biochemical effects of alcohol?
- High NADH and acetyl coA
- Inhibit GAPDH and pyruvate dehydrogenase enzymes (TCA cycle)
- Inhibit malate dehydrogenase (gluconeogenesis)
- Inhibit lactate dehydrogenase (increases lactic acid)
Describe the key features in immune cell metabolism
- They have an increased requirement for NADPH
Produced by the transport of glucose from glycolysis to the pentose phosphate pathway. This occurs in macrophages, neutraphils and activated dendritic cells.
What do immune cells use NADPH for?
As a reducing agent (NADPH oxidase)
To generate ROS.
Oxygen is reduced to free radicals and peroxide
What is respiratory burst?
When peroxide is used to kill engulfed pathogens
What is Chronic Granulomatous Disease
When ROS can not be produced in immune cells?
Name the intermediates from immune cell metabolism which are used in other pathways?
G6P—->pentose phosphate pathway
Succinly coA—->Heme—->ROS
Glutamate——>TCA—–>oxaloacetete
Which cells are energy selfish and what does this mean?
Immune cells and brain cells
Take priority over other tissues regarding energy supply
What is the WARBURG EFFECT/HYPOTHESIS and it implication in cancer metabolism?
Cancer cells take up much more glucose than normal cells ( basis of PET scan)
Glucose tends to be used for aerobic glycolysis rather than oxidative phosphorylation, which means cancer cells prefer generating ATP through glycolysis than through oxidative phosphorylation (TCA cycle) even in the presence of oxygen.
Leads to build up of lactic acid in cancer cells
What are the consequences of the Warburg effect
Cancer metabolism takes away intermediates from the TCA cycle. These have to be replaced or the cycle is left incomplete
Because cancer only uses glycolysis it uses a lot of glucose to obtain energy
