Metabolism Flashcards
What is metabolism?
All the chemical reactions in the body –> costs energy
What is anabolism?
Reactions that synthesise new (larger) molecules from smaller precursors. These need energy
What is canabolism?
Refers to reactions that break down larger molecules into smaller ones, usually to release energy
What are the absorptive and post-absorptive phases of metabolism?
- Dealing with a meal
- Maintaining homeostasis between meals
What is the fasting phase of metabolism?
Dealing with the challenge of longer periods without food
What is the intense exercise phase of metabolism?
Responding to dramatic increases in demand
What is the acute time scale of metabolism?
Minute to minute regulation of plasma glucose
What is the longer time scale of metabolism?
- Maintenance of adequate stores
- Turnover of proteins and cells
- Growth
- Reproduction
How is ATP involved in high energy reactions (e.g. glycolysis and oxidative phosphorylation)?
High energy reactions can stick a third phosphate onto ADP to form ATP.
Cells can then get that back by hydrolysing the ATP, to drive other reactions.
What do muscles contain as a short-term energy store?
Phosphocreatine
ADP + PCr –> ATP + Creatine
Creatine kinase catalyses this reaction
What do most cells convert ADP to?
ATP and AMP
ADP + ADP –> ATP + AMP
Adenylate kinase catalyses this
What is AMP a marker of?
A low-energy state
What is glycolysis?
Produces two molecules of ATP through the conversion of glucose into pyruvate, water, and NADH in the absence of oxygen.
Glycolysis is a series of reactions that extract energy from glucose by splitting it into two three-carbon molecules called pyruvates
Does glycolysis require oxygen?
No
How many ATPs get used by when preparing glucose for glycolysis?
2 but get 4 back (2 from each 1,3 DPG)
If we can handle the pyruvate aerobically, how many molecules of ATP can we get?
We get 36 more per glucose (18 per pyruvate)
What are we left with at the end of glycolysis?
2 ATP, 2 NADH, 2 pyruvate molecules
If If oxygen is available, the pyruvate can be broken down (oxidised) all the way to carbon dioxide in cellular respiration, making many molecules of ATP
How is CoA generated?
- By oxidative decarboxylation of pyruvate from glycolysis, which occurs in mitochondrial matrix
- By oxidation of long-chain fatty acids
- By oxidative degradation of certain amino acids.
Acetyl-CoA then enters in the TCA cycle where it is oxidised for energy production.
What can we make from TCA intermediates?
Fatty acids and amino acids
What is glucose only made from?
Pyruvate, and so from amino acids
Why are carbohydrates relatively inefficient as an energy store?
They bind a lot of water, making them bulky
How is glucose stored?
Glucose can be stored as polymers, mainly glycogen, in liver and muscle: this provides a rapid but relatively short-lived energy store.
Liver, but not muscle, can release glucose derived from glycogen into the circulation.
Why do fats provide a very dense energy store?
Because they don’t bind much water, and contain little oxygen.
It takes longer to re-release the energy, and it can’t be synthesised back into glucose.
What do many tissues use fatty acids as?
Their main source of energy.
What can the liver convert fatty acids into during starvation?
Ketone bodies
What are proteins mainly stored as?
Not ideal as source of energy
Mainly stored as functional proteins, so catabolism impairs cellular function.
What does the liver convert most amino acids into?
Glucose (gluconeogenesis)
What do muscle cells contain a lot of? What can it convert this to?
Protein
Can convert it to alanine and glutamine, which can be exported for gluconeogenesis.
Why are erythrocytes unable to carry out aerobic metabolism?
Lack mitochondria
Where do erythrocytes get all their energy from? Where do the waste products go?
Anaerobic glycolysis (inefficient)
“Waste” pyruvate and lactate can go back to the liver for gluconeogenesis.
Do erythrocytes have a high metabolic demand?
No
Does brain tissue have mitochondria?
No
Does brain tissue have a high metabolic demand?
Yes
What does the blood brain barrier limit?
What foodstuffs can get across.
Under normal conditions, what does the brain depend on?
The brain depends on a fairly steady plasma glucose concentration: sudden falls below about 3 mM can lead to unconsciousness and death
During fasting for several days, ketone bodies come to be an important foodstuff.
What are adipocytes?
A cell specialised for the storage of fat, found in connective tissue.
What is glucose uptake by adipose tissue sensitive to?
Insulin
What is the release of FFA and glycerol by adipose tissue sensitive to?
Glucagon
During periods of high glucose, what do adipocytes do?
Convert glucose to triglyceride
As glucose levels fall, what do adipocytes do to triglyceride?
Metabolise triglyceride to release FFA and glycerol.
What is the first “port of call” for foodstuffs absorbed from the gut?
Liver
What is glucose uptake/release by the liver sensitive to?
Uptake - insulin
Release - Glucagon
During periods of high glucose, what does the liver convert glucose to?
Glycogen
As glucose levels fall, what does the liver do?
Metabolises glycogen to release glucose
What does the liver produce ketone bodies from?
Acetyl CoA
What is gluconeogenesis?
Gluconeogenesis (GNG) is a metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates
What is the main energy source for cardiac muscle?
Fatty acids, , but can also use lactate or ketone bodies
What is glucose uptake by cardiac muscle sensitive to?
Insulin
Describe the mitochondria and myoglobin in cardiac muscle
Up to 40% mitochondria, and abundant myoglobin
Describe Type 1 skeletal muscle
Rather like cardiac muscle: highly aerobic
Adapted to prolonged, relatively modest, activity: for example, postural muscles
What is the main energy source for Type 1 skeletal muscle?
Fatty acids
Describe Type 2b skeletal muscle
“Fast-Twitch” muscle: explosive performance, but quickly fatigue. Usually only recruited for severe efforts.
Few mitochondria, and little or no myoglobin (hence white)
Phosphocreatine provides rapid replenishment of ATP, but only for a few seconds.
What does Type 2b skeletal muscle rely on?
Rely mainly on anaerobic glycolysis, with glucose coming from their glycogen store.
Adrenalin (or insulin) allow glucose uptake.
Describe Type 2a skeletal muscle
Intermediate between Type 1 and Type 2b. Contain some mitochondria, and myoglobin.
Will maintain aerobic metabolism as much as possible.
Adrenalin (or insulin) allow glucose uptake.
Describe energy store in Type 2a
Phosphocreatine and glycogen provide a good store of energy.
At lower, exercise levels, what is the main energy store in Type 2a?
Fatty acids
During fasting, what is released in Type 2a?
Release amino acids for gluconeogenesis
What happens if plasma glucose is kept high (e.g. in diabetes mellitus)?
- Osmotic effects
- Glucose lost in the urine, wasting energy and causing polyuria.
- Glycation of proteins, and later cross-linking
- microvascular and macrovascular disease
- peripheral neuropathy
- low-grade inflammatory effects
What is polyuria?
Production of abnormally large volumes of dilute urine.
What is insulin produced by?
Beta cells of the pancreas
When is insulin release stimulated?
By rise in blood glucose levels (e.g. after meal)
What is effect of insulin on blood glucose?
Insulin lowers blood glucose levels by enhancing the rate of glucose uptake and utilisation by target cells, which use glucose for ATP production
What is effect of insulin on liver?
It stimulates the liver to convert glucose to glycogen, which is then stored by cells for later use
What is effect of insulin on glucose transport?
Insulin also increases glucose transport into certain cells, such as muscle cells and the liver
This allows glucose to enter the cell, where it can be used as an energy source
What cells can access glucose without insulin?
Those in kidneys and brain
What is effect of insulin on adipocytes?
Insulin also stimulates the conversion of glucose to fat in adipocytes and the synthesis of proteins
What is diabetes mellitus caused by?
Low levels of insulin production by the beta cells of the pancreas, or by reduced sensitivity of tissue cells to insulin.
This prevents glucose from being absorbed by cells, causing high levels of blood glucose, or hyperglycemia (high sugar)
What is effect of high glucose levels on the kidneys?
- Difficult for the kidneys to recover all the glucose from nascent urine, resulting in glucose being lost in urine. - - Less water being reabsorbed by the kidneys, causing high amounts of urine to be produced; this may result in dehydration
Over time, what damage can high glucose levels cause?
Nerve damage to the eyes and peripheral body tissues, as well as damage to the kidneys and cardiovascular system.
What can oversecretion of insulin lead to?
Hypoglycemia (low blood glucose levels)
What can hypoglycemia lead to?
Insufficient glucose availability to cells, often leading to muscle weakness, and can sometimes cause unconsciousness or death if left untreated
What hormone is released when blood glucose levels drop?
Glucagon
Where is glucagon released from?
Alpha cells of the pancreas
What is effect of glucagon on blood glucose?
Glucagon raises blood glucose levels by stimulating the breakdown of glycogen to glucose in skeletal muscle cells and liver cells in a process called glycogenolysis
What is effect of glucagon on amino acids?
Stimulates absorption of amino acids from the blood by the liver, which then converts them to glucose
This process of glucose synthesis is called gluconeogenesis
What is effect of glucagon on adipose cells?
Stimulates them to release fatty acids into the blood
What is effect of thyroid hormones?
Increased general activity, basal metabolic rate
What is thyroid hormone release stimulated by?
TSH (released from anterior pituitary)
What is effect of cortisol?
Immunosuppressive effects
Effect of growth hormone on:
- Sugars
- Glycogen
- Proteins
- Fats
- Gluconeogenesis
- Synthesis
- Synthesis (increased amino acid uptake)
- Lipolysis
How is immediate energy provided in muscle?
Free ATP - this pool is very small and is quickly used up
What are the 4 sources of ADP in muscle?
- Free ATP
- Phosphocreatine
- Glycolysis
- Cellular respiration
How can phosphocreatine supply ATP to muscles?
Can rapidly donate a phosphate group to ADP to form ATP and creatine under anaerobic conditions
Can only supply muscle for 15 seconds
Is the reaction of phosphocreatine reversible?
The reaction of phosphocreatine + ADP to ATP + creatine is reversible. During periods of rest, the store of phosphocreatine is regenerated from ATP.
How is the glucose for glycolysis provided?
The glucose for glycolysis can be provided by the blood supply, but is more often converted from glycogen in the muscle fibres. If glycogen stores in the muscle fibres are expended, glucose can be created from fats and proteins. However, this conversion is not as efficient.
What is pyruvate continually processed into?
Lactic acid (this inhibits further anaerobic respiration)
While the pyruvate generated through glycolysis can accumulate to form lactic acid, what can it also be used to generate?
Further ATP
What can mitochondria in the muscle convert pyruvate into? What is required?
Mitochondria in the muscle fibers can convert pyruvate into ATP in the presence of oxygen via the Krebs Cycle, generating an additional 30 molecules of ATP.
When is cellular respiration required?
Exercising more than 30 seconds
What is cellular respiration limited by?
O2 (lactic acid can still build up)
How does cellular respiration play a role in returning muscles to normal during rest?
Converting the excess pyruvate into ATP and regenerating the stores of ATP, phosphocreatine, and glycogen in the muscle that are required for more rapid contractions.
What is glucagon?
A hormone formed in the pancreas which promotes the breakdown of glycogen to glucose in the liver.
