1. So, again, the learning objectives from the previous Primary syllabus

2. Basal Metabolic Rate So, 1st up, Basal Metabolic Rate
What do we mean by “metabolism” and “metabolic rate”?

3. What do we mean by “metabolism” and “metabolic rate”?
Catabolism: “to throw downward”
Anabolism: “to throw upward”
What is that we are actually measuring? How do we measure it?
Units?

4. SI units.
What is a gram calorie: energy needed to raise one gram of water by 1 degrees celsius at 1 atm.
What is a food Calorie: 1000 calories; 1 Cal
1 calorie = Joules
kcal?
kJ?

5. Antoine Lavoisier took an actually guinea pig…

6. “La respiration est donc une combustion, à la vérité fort lente, mais d'ailleurs parfaitement semblable à celle du charbon”
“Breathing is therefore a combustion, in fact very slow, but moreover perfectly similar to that of coal”
Antoine Lavoisier c1780
Calorimetry; calorimeters
“In 1780, Antoine Lavoisier used the heat from the guinea pig's respiration to melt snow surrounding his apparatus, showing that respiratory gas exchange is combustion, similar to a candle burning” Wikipedia
(NEXT SLIDE)
What kinds of things do we expend energy on?
Ganong
Amount of energy liberated per unit time is the “metabolic rate”
Energy liberated by catabolic processes in the body is used for maintaining body functions, digesting food, thermoregulation & physical activity.
Energy Output = External Work + Energy Storage + Heat
Isotonic contractions work at a peak efficiency of ~50%
Efficiency + [work done]/[total energy expended]
The rest appears as heat
What about isometric contractions?
External work = [force multiplied] x [distance that force moves a mass]
No movement by definition so zero external work
All the energy appears as heat
Energy storage
Formation of energy rich bonds
In fasting individuals it’s zero or negative
Adult individual who has not eaten recently, who is not moving, growing, reproducing or lactating, all of the energy output appears as heat.
How is it measured?
Direct & Indirect Calorimetry
Carbohydrates 4.1kcal/g
Fat 9.3 kcal/g
Protein 5.3 kcal/g
incomplete in vivo so 4.1 kcal/g

7. Energy Output = External Work + Energy Storage + Heat
Energy Output is the “amount energy liberated by the catabolism of food in the body”
What kinds of things do we expend energy on?
Ganong
Amount of energy liberated per unit time is the “metabolic rate”
Energy liberated by catabolic processes in the body is used for maintaining body functions, digesting food, thermoregulation & physical activity.
Energy Output = External Work + Energy Storage + Heat
Isotonic contractions work at a peak efficiency of ~50%
Efficiency + [work done]/[total energy expended]
The rest appears as heat
What about isometric contractions?
External work = [force multiplied] x [distance that force moves a mass]
No movement by definition so zero external work
All the energy appears as heat
Energy storage
Formation of energy rich bonds
In fasting individuals it’s zero or negative
Adult individual who has not eaten recently, who is not moving, growing, reproducing or lactating, all of the energy output appears as heat.
How is it measured?
Direct & Indirect Calorimetry
Carbohydrates 4.1kcal/g
Fat 9.3 kcal/g
Protein 5.3 kcal/g
incomplete in vivo so 4.1 kcal/g

8. How is it measured? (see next slide)
Conditions (oxford handbook of nutrition & dietetics):
post absorptive state (12 hours); also includes simulates such as caffeine and smoking
thermoneutral zone (20-25 degrees, comfortably warm)
supine
awake but in a state of complete physical and mental relaxation (with no caffeine!?!)
no heavy physical activity the day before
non-pregnant, phase of menstrual cycle etc
These conditions mean that no energy is being consumed in external work or storing food. So all energy consumption is converted to heat.
Sleeping generally 5-10% lower

9. Atwater-Benedict Respiration Chamber
Conditions (oxford handbook of nutrition & dietetics):
post absorptive state (12 hours); also includes simulates such as caffeine and smoking
thermoneutral zone (20-25 degrees, comfortably warm)
supine
awake but in a state of complete physical and mental relaxation (with no caffeine!?!)
no heavy physical activity the day before
non-pregnant, phase of menstrual cycle etc
These conditions mean that no energy is being consumed in external work or storing food. So all energy consumption is converted to heat.
Sleeping generally 5-10% lower
Conditions:
post-absorptive
thermo-neutral zone supine
awake
no heavy physical activity the day before
non-pregnant

10. Emotional state: probably more agitation and sympathetic outflow if “emotional”. CMRO2 probably constant.

11. Indirect calorimetry
How does it work
Energy production can also be calculated by measuring the products of the energy-producing biologic oxidations; that is, CO2, H2O, and the end products of protein catabolism produced, but this is difficult. However, O2 is not stored, and except when an O2 debt is being incurred, the amount of O2 consumption per unit of time is proportionate to the energy liberated by metabolism. Consequently, measurement of O2 consumption (indirect calorimetry) is used to determine the metabolic rate.
Multiply 4.82 kcal/L of O2 consumed. (1 calorie = Joules)
BMR: man of average size is about 2000 kcal/day. Correlates well with body surface area, but not exactly.
BMR = 3.52 x weight to the power of 0.75
Energy expenditure per time which is watts (power): joule/second; J/(h.kg)

12. Thermoneutral Zone
Not sure where in syllabus, so thought i’d mention it here.
range of ambient temperatures in which the individual maintains body temperature with minimal oxygen consumption
The thermoneutral zone is defined as the range of ambient temperatures where the body can maintain its core temperature solely through regulating dry heat loss, i.e., skin blood flow. (ie no sweating, no shivering, no change from RMR)
Online SAQ

13. What uses oxygen on either side of the TNZ?
What happens if ambient temperature above body temperature?

14. Respiratory Quotient
Steady state of the volume of CO2 produced to the volume of O2 consumed per unit time.
Respiratory exchange ratio (R): ratio of CO2 to O2 at any time whether or not equilibrium has been reached. eg exercise, acidosis, alkalosis etc range from 2.00 down to 0.
RQ for CHOs: 1.00
RQ for fat: ~0.7
RQ for Proteins 0.8
Mixed diet ~0.8
Affected by energy balance and insulin (inc sensitivity)
RQ of brain: ~
RQ of the stomach: negative as it takes up more CO2 from arteries than it puts into vein. Not really at equilibrium then, so actually R rather than RQ

15. Respiratory exchange ratio (R): ratio of CO2 to O2 at any time whether or not equilibrium has been reached. eg exercise, acidosis, alkalosis etc range from 2.00 down to 0.
RQ for CHOs: 1.00
RQ for fat: ~0.7
RQ for Proteins 0.8
Mixed diet ~0.8
Affected by energy balance and insulin (inc sensitivity)
RQ of brain: ~
RQ of the stomach: negative as it takes up more CO2 from arteries than it puts into vein. Not really at equilibrium then, so actually R rather than RQ

17. Specific Dynamic Action
Obligatory energy expenditure that occurs during its assimilation into the body
Protein has high SDA, CHOs & fats low.
“Dietary Induced Thermogenesis”
“Thermal Effect of Food”
SDA ~8%
Coffee-stimulant effect, increasing BMR
Cold water: 37kcal if you eat 1kg ice (155kJ); 1g of cadbury’s dairy milk contain 225kJ
Chewing gum?
Black coffee, especially cold drip!! Caffeine stimulant

18. Metabolic Pathways Glycolysis Citric Acid Cycle
Oxidative phosphorylation
beta-oxidation
Lactate
gluconeogenesis
ketosis

19. What’s this?
Very important molecule…will come back to this later.

20. Most reactions reversible, but not all.
Net output: 2 ATP & 2 NADH

21. Gluconeogenesis
Not quite glycolysis in reverse

23. For each molecule of Glucose entering Krebs: 8xNADH, 2xFADH2, 2xGTP, 6xCO2

25. There are also ketogenic AAs that get converted to Acetyl CoA
There are also ketogenic AAs that get converted to Acetyl CoA. (leucine; lysine)
Some are both

27. Can you tell me what this is?

28. How does it work?
Enervation?
Location?
Go back to previous slide, to show effect of UCP
Brown fat
UCP
Beige Fat
beta-3 adrenoceptors

30. Lactate
Where does lactate fit into all this?

31. Central role of Acetyl CoA
feeds into TCA
ketone bodies
ACh
fatty acid synthesis & breakdown

32. Starvation
Or as anaesthetists like to call it, “fasting”

33. I ended up on TPN but only after some delay as my electrolytes were so out of whack i was at risk of re-feeding syndrome…
“triggers synthesis of glycogen, fat and protein in cells, to the detriment of serum concentrations of potassium, magnesium, and phosphorus” Wikipedia

36. Paper 1 Q18 During periods of starvation in humans
(a) glycogen stores are depleted in 24 h
(b) amino acids are converted to glucose
(c) tissue breakdown initially provides 900 calories per day
(d) urinary nitrogen loss progressively increases
(e) a loss of 40% body cell mass is compatible with survival
a) True
b) True
c) False
d) False
e) True
Starvation is a complete absence of dietary food intake which can result in death after 60 days, in contrast to the state of malnutrition, when a calorie intake may be present. Biochemical adaptations to starvation aim to supply glucose to tissue that needs it. A patient needs 180 g glucose/day.
Changes in starvation
Glycogenolysis
First few hours
Breakdown of glycogen to glucose
Takes place in the liver
After 24 h hepatic glycogen is exhausted (b) Gluconeogenesis
Gluconeogenesis
Glucose can be formed from glycerol formed in the liver by lipolysis
Occurs as glycogen sources become depleted
Protein loss: amino acids from the muscles
pyruvate
alanine
Glucose can be formed from oxaloacetate
Ketogenesis
After about 3 days
Adipose tissue fat
FFA and ketones are the major energy sources
Later most of the body tissues, including the ketone bodies, are used as a fuel source
Glucose requirements fall
Increased ketone bodies with mild acidosis
Increased fatty acids, which inhibit gluconeogenesis
Thus body adapts to preserve proteins and use fats
Once the fat stores are depleted, protein is then mobilised to provide energy (death occurs afterwards)
Free fatty acid (FFA) used directly or indirectly as a source of energy

37. Paper 1 Q25 The respiratory quotient (RQ)
(a) is the ratio of CO2 to O2 at any given time
(b) is the ratio in the steady-state of the volume of CO2 produced
to the volume of O2 consumed per unit of time
(c) is 0.7 with a diet of carbohydrate
(d) is decreased during hyperventilation
(e) increases during severe exercise
false
true
The respiratory quotient (RQ) is the ratio of CO2 production to O2 consumption per unit time in steady state. Respiratory exchange ratio (R) is the ratio at any time not in the steady state.
R is affected by
Severe exercise (increased due to CO2 blown off and increased CO2 produced from lactic acid)
Hyperventilation (increased due to CO2 being blown off)
Post exercise (decreased as O2 dept paid)
Metabolic acidosis (increased due to respiratory compensation) Metabolic alkalosis (decreased due to respiratory compensation) Average values
CHO: 1
fat: 0.7
protein: 0.8

38. Paper 6 Q11 Basal metabolic rate
(a) is proportional to oxygen consumption
(b) is increased by dobutamine
(c) is the same obtained by measuring oxygen consumption
as by measuring heat production by calorimetric methods
(d) of a 70-kg man is 100 W or 58Wm2
(e) is twice as much, per kg, in the newborn compared to an
adult
(a) true (b) true (c) true (d) true (e) true
 Basal metabolic rate is the energy output when the body is mentally and physically at rest
 It is measured as watts 1⁄4 joules /s or W.m2
 It is increased by thyroxine and adrenaline, pregnancy and after a meal
 It is higher in the newborn and lower with old age
 It is lower in a hot climate than in a cold climate
 A calorimeter is used to measure the total heat production: as heat production is related to the oxygen consumption it is the latter that is often measured (the assumption is made that 1 l of oxygen is used to produce 4.8 kcal of energy)

39. With regard to fat metabolism
(a) fat is mainly present in the diet as triglycerides
(b) fat is absorbed by the lymphatics
(c) fat has a respiratory quotient of 1.0
(d) fat needs acetyl CoA for its metabolism
(e) insulin increases fat synthesis from glucose in the live

40. Paper 2 Q20 The following enzymes are responsible for protein
digestion
(a) gastrin
(b) amylase
(c) trypsin
(d) chemotrypsin
(e) carboxypeptidase
false
true
The enzymes responsible for protein digestion are: \
Endopeptidases, which hydrolyse interior peptide bonds of polypeptides and proteins
Trypsin attacks peptide bonds involving basic amino acids
Chymotrypsin attacks peptide bonds involving aromatic amino acids, leucine, glutamine and methionine
Elastase attacks peptide bonds involving neutral aliphatic amino acids
(b) Exopeptidases, which hydrolyse external peptide bonds of polypeptides and proteins
Carboxypeptidase A
Carboxypeptidase B.

41. Paper 3 Q19 Lactic acid is (a) formed during anaerobic ATP resynthesis
(b) increased in concentration in the blood during an energy
deficit
(c) not formed in red cells
(d) converted to glucose by the Cori cycle
(e) oxidised without conversion back to glucose
true
false
Normal blood lactate is 0.6–1.2 mmol/l and levels above 5 mmol/l cause a significant acidosis. Concentrations greater than 1(0) mmol/l carry an 80% mortality rate.
Lactate is made in skeletal muscle and red blood cells. When oxygen supplies are limited pyruvate is reduced to NADH to form lactate. The reaction is catalysed by lactate dehydrogenase.
The importance of this reaction is that it produces two molecules of ATP. It generates NADþ, which sustains continued glycolysis in skeletal muscle and erythrocytes under anaerobic conditions.
The limiting factor is the liver, which must oxidise lactate back to pyruvate for subsequent gluconeogenesis in the Cori cycle. This pathway merely buys time during the period of anaerobic metabolism.

42. Paper 4 Q15
Fasting for longer than 24 h is associated with
. (a)  increased hepatic glycogenolysis
. (b)  increased hepatic gluconeogenesis
. (c)  increased protein catabolism
. (d)  increased muscle gluconeogenesis
. (e)  ketoacidosis
false
true
The liver glycogen stores are depleted within 24 h. Muscle, protein and fat are mobilised as energy sources in the process of gluconeogenesis. Gluconeogenesis takes place in the liver and a small amount in the kidney. Other organs can utilise lactate. Ketoacidosis occurs in starvation and diabetes mellitus when the breakdown of fats exceeds the breakdown of carbohydrates. Then the supply of acetyl coenzyme from fl oxidation exceeds the rate at which oxaloacetic acid can be formed in the tricarboxylic acid cycle. So the acetyl-coenzyme A that cannot enter the cycle is formed into ketone bodies. These ketone bodies, acetone, acetoacetic acid and beta- hydroxyl butyric acid, are used for energy in cardiac muscle and the renal cortex where they are converted back into acetyl coenzyme A.