Metabolism

Question 1

Explain the different types of work done in the body

Answer 1

Question 2

Explain the first and second laws of thermodynamics

Answer 2

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)

Question 3

Define metabolic rate and basal metabolic rate

Answer 3

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)

Question 4

Compare and contrast the macronutrients

Answer 4

Question 5

Explain the difference. between catabolism and anabolism

Answer 5

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

Question 6

List the 7 factors which influence BRM and what processes are used to measure it

Answer 6

1. Age
2. Biological sex
3. Amount of lean muscle mass
4. Activity level
5. Diet and diet-indiced thermogenesis
6. Hormones
7. Genetics

Question 7

What role does the liver play in energy metabolism within the body?

Answer 7

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)

Question 8

What role does glycogen play in the body and what is the difference between glycogenolysis and glycogenesis?

Answer 8

Glycogen is a form of energy storage in the body which can be readily broken down into glucose and used for metabolism

Question 9

What is special about the metabolic demands of the brain and kidneys?

Answer 9

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

Question 10

Differences between muscle and adipose tissue in relation to metabolism?

Answer 10

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)

Question 11

Explain nutrient pools and metabolism

Answer 11

Question 12

What are the 3 fates of ingested biomolecules?

Answer 12

1. Provide energy to do mechanical or other work
2. Used for synthesis for growth and maintainance
3. Storage as glycogen or fat

Question 13

Explain metabolic pathways

Answer 13

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

Question 14

Compare and contrast endergonic and exergonic reactions in terms of free energy changes and the likelihood that they will proceed

Answer 14

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)

Question 15

Explain what is menat by the activation energy of a reaction

Answer 15

The amount of input energy required for a reaction to occur

Question 16

Describe why ATP is considered to be an ‘energy currency’ and what makes it able to act in this way

Answer 16

ATP contains high-energy phosphate bonds. Removal of a phosphate via hydrolysis releases energy which can be used in other organic coupled reactions

Question 17

How are glycolysis, the TCA cycle and oxidative phosphorylation linked?

Answer 17

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

Question 18

Explain why aerobic metabolism is more efficient than anaerobic metabolism in yielding ATP

Answer 18

Question 19

Why can either supplying alot of substrate or removing a product improve the flow through a metabolic pathway

Answer 19

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

Question 20

Why do products of metabolic pathways often inhibit the first commited step in the pathway by which they are synthesised?

Answer 20

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

Question 21

Explain how cells control metabolic pathways involving the same steps operating in different directions

Answer 21

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)

Question 22

What pathways are active for glucose and amino acid metabolism in the fed state of metabolism?

Answer 22

Question 23

Compare and contrast glycogenesis and glyconeogenesis

Answer 23

Question 24

How is metabolism regulated at the level of enzymes?

Answer 24

1. Different enzymes are often used to catalyse reactions in different directions
2. Different isozymes (distinct enzymes that catalyse the same reaction) can be used to catalyse a reaction in different tissues with diverse physiological requirements
3. Compartmentalisation of organelles and tissues can allow regulation of their activities

Question 26

Describe what happens to glucose and amino acids after a meal, naming the pathways that occur in the liver, muscle and adipose tissue

Answer 26

Question 27

Explain the pathway by which triglycerides in the intestine are metabolised and stored as triglycerides in adipose tissue

Answer 27

1. Bile salts emulsift dietary fats in the SI, forming micelles
2. Intestinal lipases degrade triglycerols
3. FAs and other breakdown products are taken up by the intestinal mucosa and converted into triacylglycerols
4. Triglycerides are incorperated with cholesterol and apolipoproteins into chloromicrons
5. Chloromicrons move through the lymphatic system and bloodstrean to tissues
6. Lipoprotein lipase convertes triglycerides into into FFAs and glycerol in the bloodstream

Question 28

Explain how cholesterol is absorbed and transported to tissues for use in membranes and for bile salt and hormone synthesis

Answer 28

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

Question 29

What is the defference between HDLs and LDLs in tems of their chemical composition and relationship to heart disease?

Answer 29

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

Question 30

Explain why most lipids have an even number of carbons

Answer 30

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

Question 31

Explain how excess glucose can be converted to triglycerides

Answer 31

Question 32

How does glycogenolysis differ in the liver and muscle

Answer 32

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

Question 33

Describe how triglycerides are broken down in the fasting state, naming the pathways involved

Answer 33

Broken down via lipolysis

Glycerol feeds into glycolysis

FA’s enter beta-oxidation to produce acetyl CoA

Question 34

Describe how proteins are broken down in the fasting state, naming the pathways involved

Answer 34

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

Question 35

Name the three intermediary metabolites that can be used for gluconeogenesis

Answer 35

Amino acids, pyruvate and lactate

Question 36

Explain the conditions under which ketone body formation occurs

Answer 36

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

Question 37

Explain the potential risks of the ketogenic diet

Answer 37

Question 38

Compare and contrast the effects of insulin and glucagon on energy metabolism

Answer 38

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

Question 39

Explain how glucose is taken up in different tissues, specifying the transporters involved and the effect of insulin on them

Answer 39

Question 40

How does glucagon protect against hypoglycaemia?

Answer 40

Glucagon acts on liver to increase glycogenolysis and gluconeogenesis

Question 41

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

Answer 41

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

Question 42

What is meant by metabolic syndrome?

Answer 42

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

Question 43

Describe the thermoregulatory reflexes in the body which maintain temperature homeostasis

Answer 43

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)

Question 44

Explain what is meant by non-shivering thermogenesis, shivering thermogenesis, the thermoneutral zone, and core temperature

Answer 44

Normal metabolism generates enough heat to maintain body temperature in the thermoneutral zone (27.8-30C)