Metabolism Flashcards
Explain the different types of work done in the body
Explain the first and second laws of thermodynamics
First law of thermodynamics - energy cannot be created or destroyed but just transformed from one form to another
Second law of thermodynamics - no conversion of energy is 100% efficient, some is always lost as heat. Without an input of energy, a system will always move from a state of order to a state of disorder (entropy)
Define metabolic rate and basal metabolic rate
MR - the rate at which energy is spent in the body in a given period of time (kcal/hr or kcal/day)
BMR - is measured under ideal, basal conditions
- Physical and mental rest; no food within 12hr (no energy expenditure for digestion)
- Conformable room temperature (~25C, i.e. no sweating or shivering)
Compare and contrast the macronutrients
Explain the difference. between catabolism and anabolism
Metabolism = catabolic reactions + anabolic reactions
Catabolic reactions break down larger molecules, such as carbs, lipids and proteins from ingested food, into smaller parts
Anabolic reactions or biosynthetic reactions, synthesise larger molecules from smaller constituent parts, usually using ATP as the energy source
List the 7 factors which influence BRM and what processes are used to measure it
- Age
- Biological sex
- Amount of lean muscle mass
- Activity level
- Diet and diet-indiced thermogenesis
- Hormones
- Genetics
What role does the liver play in energy metabolism within the body?
Intestinal blood supply flows directly to the liver, therefore it gets the majority of nutrients/metabolites directly after they’re absorbed
Liked closely to pancreatic blood supply - insulin/glucagon hormones exert their effects in the liver first
Stored glucose as glycogen (glycogenesis) which it can breakdown when required (glyconeogenesis) and release to the rest of the body
Can synthesise glucose form amino acids (gluconeogenesis)
Can synthesise ketones, from FAs and amino acis (ketogenesis) as an alternative energy source when carbs are scarce
Can synthesise lipids (FAs and triglycerides) from glucose and amino-acids (lipogenesis)
What role does glycogen play in the body and what is the difference between glycogenolysis and glycogenesis?
Glycogen is a form of energy storage in the body which can be readily broken down into glucose and used for metabolism
What is special about the metabolic demands of the brain and kidneys?
The brain has a very high metabolic rate (blood supply 50ml/100g/min vs 2-5ml/100g/min in resting skeletal muscle) and depends almost entirelt on glucose (can use ketone bodies in starvaiton). It oxidises ~120g of glucose per day at a stable rate (wide variation in blood glucose has little effect on brain uptake unless severly low).
The kidneys also have a very high metabolic rate. They constitute only 0.5% of body mass, but consume 105 of the O2 used in cellular respiration. FIlter out urea and recover metabolises such as glucose
Differences between muscle and adipose tissue in relation to metabolism?
Muscle tissues is the major mass tussue (~40% bw) and utilises glucose as energy source during fed state and activity, utilises lipids during fasting.
Adipose tissue is a key metabolic regulator of lipid storage and release. Store FAs as triglycerides, releases FAs. Not all fat depots the same (sub-cutaneous vs visceral, white vs brown)
Explain nutrient pools and metabolism
What are the 3 fates of ingested biomolecules?
- Provide energy to do mechanical or other work
- Used for synthesis for growth and maintainance
- Storage as glycogen or fat
Explain metabolic pathways
Involve chemical reactions, usually catalysed by enzymes
Molecules are converted to other molecules by breakage of covalent bonds between atoms
These reactions occur in a defined order and are subject to regulation at various points
- Primary metabolism is the set of reactions that are required for growth and replication (e.g. common to most or all types of cells)
- Secondary metabolic pathways are those that involve hormones ans other more specialised chemicals that are found in more restricted groups of organisms
- Intermediary metabolism is all reactions concerned with the storage and generation of metabolic energy required for the biosynthesis of low molecular weight compounds and energy storage compounds
Compare and contrast endergonic and exergonic reactions in terms of free energy changes and the likelihood that they will proceed
Exergonic reactions are thermodynamically favourable and will occur spontaneously
Endergonic reactions will require the input of energy to proceed (or a very large/infinite difference in the concentration of substrates and products)
Explain what is menat by the activation energy of a reaction
The amount of input energy required for a reaction to occur
Describe why ATP is considered to be an ‘energy currency’ and what makes it able to act in this way
ATP contains high-energy phosphate bonds. Removal of a phosphate via hydrolysis releases energy which can be used in other organic coupled reactions
How are glycolysis, the TCA cycle and oxidative phosphorylation linked?
Glycolysis and the citric acid cycle produce small amounts of ATP directly, but their most important contributions to ATP synthesis are high-enery electrons carried by NADH and FADH2 to the electron transport system in the mitochondria
Explain why aerobic metabolism is more efficient than anaerobic metabolism in yielding ATP
Why can either supplying alot of substrate or removing a product improve the flow through a metabolic pathway
Increases in substrates or removal of products imrpves flow through a metabolic pathway accorting to le Chatelier’s principle. Reactions at equilibrium shift to counteract any changes put upon them
Why do products of metabolic pathways often inhibit the first commited step in the pathway by which they are synthesised?
Feedback inhibition allows metabolism to be coordinated in its response under certain conditions. For example, if there is too much product in pathway A and not enough in pathway B, feedback inhibition can slow the production rate in pathway A and increase the production rate in pathway B
Explain how cells control metabolic pathways involving the same steps operating in different directions
Different enzymes are often used to catalyse reactions in different directions. Under different physiological states, their activity can be activated, inactivated or modualted (up- and down-regulated). The activity of enzymes can be affected by: Physiochemical conditions –> temperature and pH; Modification of the enzyme structure (e.g. by phosphorylation or cleavage); The binding of small molecules to the enzyme to alter its activity (can inhibit certain pathways as seen in feedback inhibition)
What pathways are active for glucose and amino acid metabolism in the fed state of metabolism?
Compare and contrast glycogenesis and glyconeogenesis
How is metabolism regulated at the level of enzymes?
- Different enzymes are often used to catalyse reactions in different directions
- Different isozymes (distinct enzymes that catalyse the same reaction) can be used to catalyse a reaction in different tissues with diverse physiological requirements
- Compartmentalisation of organelles and tissues can allow regulation of their activities
Describe what happens to glucose and amino acids after a meal, naming the pathways that occur in the liver, muscle and adipose tissue
Explain the pathway by which triglycerides in the intestine are metabolised and stored as triglycerides in adipose tissue
- Bile salts emulsift dietary fats in the SI, forming micelles
- Intestinal lipases degrade triglycerols
- FAs and other breakdown products are taken up by the intestinal mucosa and converted into triacylglycerols
- Triglycerides are incorperated with cholesterol and apolipoproteins into chloromicrons
- Chloromicrons move through the lymphatic system and bloodstrean to tissues
- Lipoprotein lipase convertes triglycerides into into FFAs and glycerol in the bloodstream
Explain how cholesterol is absorbed and transported to tissues for use in membranes and for bile salt and hormone synthesis
LDL-C brings cholesterol from liver to most cells to be used in membranes and for synthesis of molecules such as hormones
HDL-C transports cholesterol out of plasma into the liver where it can be metabolised and used to produce bile salts (cholesterol + FFA + lipoproteins = bile salts)
Oxidised LDL-C taken up by macrophages into atherosclerotic plaques which are stored in the bloodstream, block blood vessels
What is the defference between HDLs and LDLs in tems of their chemical composition and relationship to heart disease?
In a molecule of LDL, approximately 50% of the weight is cholesterol and 25% is protein. Alternatively, in a molecule of HDL, appproximately 20% of the weight is cholesterol and 50% protein, making it more dense.
Oxidised LDL-C taken up by macrophages into atherosclerotic plaques which are stored in the bloodstream, block blood vessels
Ratio of types of cholesterol is indicator of risk of coronary heat disease
High LDL-C or low HDL-C indicates increased risk of atherosclerosis and coronary heart disease
Explain why most lipids have an even number of carbons
Excess glucose can be converted to fat via lipogenesis. FAs are made when 2-carbon acyl from acetyl CoA are linked together. Therefore biosynthesised lipids can only have an even number of carbons
Cholesterol mostly from diet but can also be synthesised from acetyl CoA
Explain how excess glucose can be converted to triglycerides
How does glycogenolysis differ in the liver and muscle
In liver, glycogen is broken down to glucose
Muscle and most other tissues lack Glucose-6-phosphatase so glycogen is broken down to glucose-6-phosphate
Glucose-6-phosphate is then metabolised to pyruvate or lactate in muscle
Pyruvate and lactate are then transported to the liver where they are used to make glucose via gluconeogenesis
Describe how triglycerides are broken down in the fasting state, naming the pathways involved
Broken down via lipolysis
Glycerol feeds into glycolysis
FA’s enter beta-oxidation to produce acetyl CoA
Describe how proteins are broken down in the fasting state, naming the pathways involved
Broken down by proteases to amino acids
Amino acids are deaminated to organic acids: pyruvate, acetyl CoA, and intermediates of the citric acid cycle
These can be broken down with production of ATP
Pyruvate can be used for gluconeogenesis
Name the three intermediary metabolites that can be used for gluconeogenesis
Amino acids, pyruvate and lactate
Explain the conditions under which ketone body formation occurs
In prolonged fasting, TCA cycle intermediates are depleted (because they are used for gluconeogenesis) so acetyl CoA cannot enter the TCA cycle
- Liberates built-up acetyl CoA and fuels the brain
Excess acetyl CoA which builds up is used to make ketone bodies
Leads to ketoacidosis
Ketogenic diets are rich in proteins and fats but low in carbohydrates
Explain the potential risks of the ketogenic diet
Compare and contrast the effects of insulin and glucagon on energy metabolism
Metabolism is controlled primarily by the balance between the short-lived hormones insulin and glucagon. Insulin is dominant in the fed state, increasing glucose oxxidation and synthesis, fat synthesis and protein synthesin. Glucagon is dominant in the fasted state, increasing glycogenolysis, gluconeogenesis and ketogenesis
Explain how glucose is taken up in different tissues, specifying the transporters involved and the effect of insulin on them
How does glucagon protect against hypoglycaemia?
Glucagon acts on liver to increase glycogenolysis and gluconeogenesis
Compare type I and II diabetes in terms of the age of onset, reason for the lack of effect of insulin and severity of symptoms
Diabetes Mellitus is a family of diseases characterised by hyperglycaemia (abnormally high blood glucose)
Type 1 - characterised by insulin deficiency from pancreas beta cells destruction
Often develpoed in childhood, genetic predisposition
Without insulin cells go into fasted-state metabolism
- Protein and fat breakdown,
- Hyperglycaemia, glucose in urine (glucosuria),
- Excessive eating (polyphagia),
- Excessive urination and thirst,
- Metabolic acidosis (from ketone bodies)
Type 2 - know as insulin-resistant diabetes wherin target cell responsiveness is decreased
90% of all cases of diabetes, often developed later in life and commonly associated with obesity and metabolic syndrome
Usually some insulin still remains: insulin levels may be normal to high or reduced
Glucagon levels are often high (alpha cells require insulin for glucose uptake) which increases hyperglycaemia
Hyperglycaemia common but ketosis uncommon
Atherosclerosis, neurological changes, renal failure, diabetic retinopathy
Up to 70% of patients will die of CV disease
Therapy: exercise and weight loss, drugs
What is meant by metabolic syndrome?
People who are overweight are at risk of developing type II diabetes, atherosclerosis and high BP
Metabolic syndrome = 3 of the following
- Central (visceral) obesity (>40 inches in men, >35 inches in women)
- BP of >130/85 mm Hg
- Fasting plasma glucose >110 mg/dL
- Elevates fasting plasma triglycerides
- Low plasma HDL-C levels
Elevated risk of type II diabetes, stroke and heard disease
Describe the thermoregulatory reflexes in the body which maintain temperature homeostasis
Maximise heat loss:
- Vasodilation of cutaneous blood vessels
- Increased sweating
- Behavioural responses (i.e. fan, water, removing clothes)
Minimise heat production:
- Diminish food intake to lessen obligatory heat produciton
- Behavioural responses (i.e. decreased physical activity)
Minimise heat loss:
- Vasoconstriction of cutaneous blood vessels
- Lack of sweating
- Behavioural responses (i.e. adding layers of clothes, curling up, standing near heat source)
Maximise heat production:
- Shivering thermogenesis
- Nonshivering thermogenesis
- Behavioral responses (increased volunatary activity)
Explain what is meant by non-shivering thermogenesis, shivering thermogenesis, the thermoneutral zone, and core temperature
Normal metabolism generates enough heat to maintain body temperature in the thermoneutral zone (27.8-30C)
