Session 6: Adaptations of Metabolism

Question 1

Give three examples of states which can lead to alterations in metabolism.

Answer 1

1) Pregnancy
2) Various types of exercise
3) Feeding/fasting and starvation

Question 2

Pregnancy is a ___ and ___ demanding state.

Answer 2

Pregnancy is a nutrient and energy demanding state.

Question 3

During pregnancy, there is a progressive increase in the requirements for the developing ___ and ___.

Answer 3

During pregnancy, there is a progressive increase in the requirements for the developing foetus and placenta.

Question 4

During pregnancy, most substances cross the placenta by ___ and ___ ___.

Answer 4

Passive and facilitated diffusion.

Question 5

The transfer of a MINORITY of substances such as amino acid transport to the placenta are conducted by…

Answer 5

Active transport.

Question 6

What is the principal fuel for the developing foetus during pregnancy?

Answer 6

Glucose.

Question 7

What is the primary glucose transporter which transfers glucose to the foetus via the placenta?

Answer 7

GLUT1 transporter.

Question 8

Specialised epithelial cells found in the outermost layer of the placenta which facilitates transfer of metabolites, drugs, waste, gases between foetal and maternal circulation.

Answer 8

Syncytiotrophoblasts (SYN).

Question 9

What are the two main phases of metabolic adaptation during pregnancy?

Answer 9

1) The anabolic phase = preparatory increase in maternal store of nutrients

2) The catabolic phase = increase in the AVAILABILITY of nutrients in the blood.

Anabolic Phase (First Half of Pregnancy): During this phase, the body focuses on building up energy stores, including increased fat storage, and growth of maternal tissues (like the uterus and breasts) to support fetal development.

Catabolic Phase (Second Half of Pregnancy): In this phase, the body breaks down stored nutrients, especially fats, to provide energy for both the mother and the growing fetus, supporting the increased metabolic needs as the pregnancy progresses.

Question 10

Briefly explain the changes which occur during the first phase of metabolic changes during pregnancy (anabolic phase).

Answer 10

• First half of pregnancy
• Maternal fat stores increase
• Increased insulin levels and increase in insulin sensitivity = help achieve increase in maternal fat stores
• These changes meet the demand of the growing fetus in late pregnancy, birth & lactation.

Question 11

Briefly explain the changes which occur during the second phase of metabolic changes during pregnancy (catabolic phase).

Answer 11

• Second half of pregnancy
• Increase in maternal nutrients available in the blood (glucose, free fatty acids, ketones)
• Decreased insulin sensitivity or increased insulin resistance = help achieve increased availability of maternal nutrients such as glucose for benefit of fetal growth in late pregnancy (when most of the foetal growth occurs).

Question 12

Foetal-placental unit.

Answer 12

The system which the fetus is under the influence of.

Question 13

What does the foetal-placental unit consist of?

Answer 13

1) Foetal hormones
2) Placental hormones
3) Maternal hormones.

Question 14

Foetal hormones.

Answer 14

Produced by endocrine gland (steroid hormones).

Question 15

Placental hormones.

Answer 15

1) Chorionic gonadotropin (HCG)
2) Corticotropin releasing hormone (CRH)
3) Placental lactogen (PL)
4) Oestrogen
5) Progesterone.

Question 16

Maternal hormones.

Answer 16

Insulin
Glucagon
Cortisol.

Question 17

What are the anti-insulin hormones in pregnancy?

Answer 17

The hormones which exert an ‘anti-insulin’ effect.

Placenta secretes (e.g:- CRH) which exerts anti-insulin effect by impairing glucose uptake into muscles and adipose.

Question 18

Which placental hormones have an ‘anti-insulin’ effect?

Answer 18

1) Corticotropin releasing hormone (CRH)
2) Placental lactogen (PL)
3) Oestrogen
4) Progesterone.

Question 19

What effect does the ‘anti-insulin’ effect exerted by placental hormones have on maternal metabolism?

Answer 19

1) Reduced maternal glucose uptake in adipose and muscle tissue
2) Allow more glucose to be available for the fetus.

Question 20

What can sometimes occur as an impact of the ‘anti-insulin’ effect during pregnancy?

Answer 20

Transient hyperglycaemia due to the enhanced insulin resistance (due to production of anti-insulin hormones during pregnancy).

Question 21

During late pregnancy, blood glucose is ~10% ___ as the insulin levels are ~1.65x ___ in fasting state and ~3x ___ in postprandial state.

Answer 21

During late pregnancy, blood glucose is ~10% lower as the insulin levels are ~1.65x higher in fasting state and ~3x higher in postprandial state.

Question 22

Episodes of ___ can occur between meals and at ___ due to continuous usage of glucose by the fetus.

Answer 22

Episodes of hypoglycaemia can occur between meals and at night due to continuous usage of glucose by the fetus.

Question 23

Generally, mothers experience an increased ___ during pregnancy as a symptom.

Answer 23

Appetite.

Question 24

Which hormones increase the sensitivity of maternal pancreatic B-cells to blood glucose?

Answer 24

Oestrogen and progesterone increase the sensitivity of maternal pancreatic B-cells to blood glucose.

Question 25

Collectively, the changes to maternal B-cells during pregnancy (increased sensitivity to blood glucose) leads to an increased production of ___ hormone.

Answer 25

Insulin.

Question 26

If maternal B-cells do not respond normally during pregnancy, blood glucose levels can become VERY ___.

Answer 26

Elevated.

Question 27

What condition can occur as a result of abnormal response of maternal B-cells during pregnancy?

Answer 27

Gestational diabetes.

Question 28

Gestational diabetes.

Answer 28

Form of **diabetes mellitus** occurring during pregnancy in which **maternal pancreatic B-cells do not produce sufficient insulin** to meet requirements of the fetus during late pregnancy.

Question 29

Fasting plasma glucose during gestational diabetes.

Answer 29

>5.6 mmol/L.

Question 30

List three known and underlying causes of gestational diabetes.

Answer 30

1) **B-cell dysfunction** associated with **obesity** and **chronic insulin resistance** (similar to T2D) = most common 2) **Autoantibodies** produced (similar to T1D) 3) Genetic susceptibility (similar to maturity-onset diabetes).

Question 31

Most common CAUSE of gestational diabetes.

Answer 31

B-cell dysfunction associated with obesity and chronic insulin resistance (similar to T2D).

Question 32

Most rare CAUSE of gestational diabetes.

Answer 32

Genetic susceptibility (similar to maturity-onset diabetes) = occurs in 1-5% cases.

Question 33

How many pregnancies does gestational diabetes affect?

Answer 33

3-10% pregnancies.

Question 34

What complications can gestational diabetes increase the risk of occurring?

Answer 34

1) **Miscarriage** 2)** Congenital malformation** (risk 4x higher) 3) **Foetal macrosomia** (large baby) - increased risk of foetal shoulder dystocia 4) Hypertensive disorders of pregnancy = gestational hypertension & pre-eclampsia.

Question 35

What potential complications can occur as a result of gestational diabetes to the FETUS?

Answer 35

1) Miscarriage 2) Congenital malformation of fetus (4x higher) 3) Foetal macrosomia - shoulder dystocia of fetus.

Question 36

What potential complications can occur as a result of gestational diabetes to the MOTHER?

Answer 36

1) **Increased risk of hypertensive disorders** of pregnancy including = gestational hypertension and pre-eclampsia.

Question 37

Indications of pre-eclampsia in mother. (high blood pressure)

Answer 37

High BP Proteinuria.

Question 38

What is a good predictor of risk of developing gestational diabetes BEFORE pregnancy?

Answer 38

Measuring insulin resistance in woman BEFORE pregnancy.

Question 39

A woman who is at high-risk of developing gestational diabetes will have ___ insulin resistance before pregnancy.

Answer 39

Higher.

Question 40

A woman who is at low-risk of developing gestational diabetes will have ___ insulin resistance before pregnancy.

Answer 40

Lower.

Question 41

Majority of women who have gestational diabetes go on to develop type ___ diabetes later in life.

Answer 41

Type 2 diabetes.

Question 42

Risk factors for gestational diabetes in mother.

Answer 42

1) **Maternal age >25** 2) **BMI >25 kg/m^2** 3) Race/ethnicity = more common in black/hispanic/asian 4) **Personal/family history** = diabetes, macrosomia.

Question 43

Management of gestational diabetes.

Answer 43

1) **Dietary modification in obese women** = reduce calories 2) **Insulin injections** = persistent hyperglycaemia 3) Regular **ultrasounds to monitor fetus**.

Question 44

What is considered 'hyperglycaemic' levels of glucose in a pregnant women (bloods)?

Answer 44

7.5-8 mmol/L post-prandial glucose >5.5-6 mmol/L fasting glucose.

Question 45

Some benefits of exercise.

Answer 45

1) **Improved body composition** = increased muscle, decreased adipose 2) **Improved glucose tolerance** = increase muscle glycogenesis 3) **Increased insulin sensitivity** in tissues 4) **Decrease in blood triglyceride levels** (decreased VLDL + LDL; increased HDL) 5) **Decreased BP** 6) **Psychological benefits**.

Question 46

The switch from a state of rest to exercise causes RAPID changes in which systems?

Answer 46

1) MSK 2) CVS 3) Respiratory system 4) Temperature regulation system.

Question 47

During exercise, the metabolic response needs to ensure four things. What are they?

Answer 47

1) **Increased energy demand** of skeletal/cardiac muscle are **met** 2) **Minimal disturbance** to metabolic **homeostasis** 3) **Glucose** supply to **brain** is **maintained** 4) **End products** of **metabolism removed** ASAP.

Question 48

What three factors does the metabolic response to exercise depend on?

Answer 48

1) Type of exercise (type of muscle used) 2) Intensity, duration 3) Physical/nutritional state of individual.

Question 49

ATP stores in muscles are ___ (~5mmol/L) which lasts for ~___ during a 100m sprint.

Answer 49

ATP stores in muscles are limited (~5mmol/L) which lasts for ~2 seconds during a 100m sprint.

Question 50

ATP must be rapidly regenerated during exercise at a rate that meets the increased metabolic demands of tissues that require it. Cells will take on different metabolic strategies so that the regeneration rate of ATP matches the rate of...

Answer 50

Hydrolysis of ATP.

Question 51

Sources of ATP during exercise.

Answer 51

1) Muscle **creatine phosphate stores** Creatine phosphate to creatine ( therefore ADP to ATP) 2) **Glycolysis** (inefficient; 2ATP per cycle) 3) **Oxidative phosphorylation** (efficient; but requires oxygen) 4) **Breakdown of muscle glycogen** (glycogenolysis).

Question 52

Muscle creatine phosphate stores.

Answer 52

~17 mmol/kg muscle rapidly replenishes ATP providing immediate energy lasts only ~5 seconds.

Question 53

Glycogenolysis can sustain what type of exercise and for what duration?

Answer 53

Breakdown of muscle glycogen (glycogenolysis) can sustain **high intensity exercise** under **anaerobic conditions** for up to ~**2 minutes**.

Question 54

In case of low-intensity exercise, what duration of this low-intensity exercise could glycogenolysis provide energy for?

Answer 54

If exercise is of low intensity - enough O2 can be provided for complete oxidation of glycogen and glucose stores in muscle to provide energy for ~60 minutes (e.g., jogging).

Question 55

Muscle glycogen is broken down into ___ during glycogenolysis. This takes place in the liver.

Answer 55

Glucose-6-phosphate.

Question 56

What enzyme catalyses the conversion of glycogen to glucose-6-phosphate during glycogenolysis?

Answer 56

Glycogen phosphorylase. ## Footnote Stimulated by: - Adrenaline - AMP.

Question 57

Key regulating enzyme in glycolysis.

Answer 57

Phosphofructokinase.

Question 58

Pyruvate can enter the TCA cycle in ___ conditions.

Answer 58

Aerobic.

Question 59

Lactate is the end-product of glycolysis under ___ conditions.

Answer 59

Anaerobic.

Question 60

What organ is responsible for regulating blood glucose levels in the body and making glucose available for peripheral tissues (especially the brain)?

Answer 60

Liver.

Question 61

Exercise results in an increase in hepatic blood glucose production in the liver via ___ and ___.

Answer 61

Glycogenolysis and gluconeogenesis.

Question 62

The ___ recycles lactate produced by ___ metabolism in the ___ cycle.

Answer 62

The liver recycles lactate produced by anaerobic metabolism in the cori cycle.

Question 63

Muscle takes up blood glucose via insulin-dependent ___ transporter.

Answer 63

GLUT4.

Question 64

Exercising muscle uses insulin-___ process of glucose uptake.

Answer 64

Independent.

Question 65

___ stores in adipose tissue provide the muscle with ___ acids.

Answer 65

Triacylglycerol stores in adipose tissue provide the muscle with fatty acids.

Question 66

Oxidation of fatty acids could provide enough energy for up to...

Answer 66

~48 hours of low-intensity aerobic exercise.

Question 67

Pros of fatty acid metabolism in exercise.

Answer 67

**High capacity for sustained production** ~48 hours of low-intensity aerobic exercise.

Question 68

Cons of fatty acid metabolism in exercise.

Answer 68

- **Low rate of ATP production** - Can only be used in **aerobic conditions** - **Slow release** from adipose tissue (not immediate) - Limited carrying capacity in the blood - **Limited rate of FA uptake across mitochondrial membrane (carnitine shuttle transporter) for B-oxidation**.

Question 69

100m sprint (short duration, high intensity).

Answer 69

Primarily anaerobic (cannot deliver sufficient oxygen to muscles in time). Creatine phosphate stores are used up, then glycogen converted to glucose 6 phosphate which enters ANAEROBIC glycolysis

Question 70

100m sprint energy sources.

Answer 70

1) High-energy creatine phosphate stores (~5 seconds) 2) Muscle glycogenolysis to glucose-6-phosphate which is then metabolised in anaerobic glycolysis 3) Production of lactate from anaerobic glycolysis - build up of [H+] leading to muscle fatigue.

Question 71

1500m middle distance.

Answer 71

Medium duration, medium intensity. ## Footnote ~40% of metabolism is anaerobic. Remaining is aerobic via glucose and FA metabolism.

Question 72

Three phases of the 1500m middle distance exercise?

Answer 72

1) Initial start = muscle uses creatine phosphate & glycogen stores & glycolysis (anaerobic) 2) Long middle phase = **ATP produced aerobically via glucose & FA oxidation** 3) Final finishing sprint = **anaerobic metabolism reliance again** (muscle glycogen & glycolysis).

Question 73

Marathon energy sources.

Answer 73

95% aerobic metabolism using... 1) Glucose: muscle & liver glycogen 2) Fatty acid oxidation.

Question 74

In the marathon, what is the order of energy source depletion?

Answer 74

1) Muscle glycogen depleted in minutes 2) Blood glucose from liver glycogen peaks at 1 hour 3) Use of fatty acids steadily increases from 20-30 minutes.

Question 75

Hormones which control the metabolic response to exercise.

Answer 75

Question 76

Why do tissues switch from glucose → fatty acid/ketone metabolism during starvation/fasting?

Answer 76

To conserve glucose for the brain.

Question 77

The brain ___ use fatty acids but __ use ketone bodies as an alternative source of energy.

Answer 77

The brain cannot use fatty acids but can use ketone bodies as an alternative source of energy.

Question 78

Glucose for the brain comes from...

Answer 78

Gluconeogenesis. 1) From glycerol 2) From amino acids.

Question 79

Name a state in which insulin sensitive tissues do not respond well to insulin.

Answer 79

Insulin resistance.

Question 80

Insulin sensitivity is decreased in early pregnancy. True or false?

Answer 80

False.

Question 81

What is a primary fuel for the foetus?

Answer 81

Glucose.

Question 82

What is the most likely metabolic pathway involved during short and intense exercise?

Answer 82

Glycogenolysis and glycolysis.

Question 83

Which ones of the following are the first fuels for exercising muscle during a sprint? a) Muscle ATP and creatinine phosphate b) creatinine phosphate and ketone bodies c) Muscle ATP and creatine phosphate d) Muscle ATP and fatty acids.

Answer 83

c) Muscle ATP and creatine phosphate.

Question 84

During a sprint skeletal muscle works under anaerobic conditions and during a marathon run skeletal muscle works mainly under aerobic conditions. True or false?

Answer 84

True.