Metabolism in Health

Question 1

What are the two states of metabolism

Answer 1

• fed (absorptive) state (shortly after meal when new nutrients are available)
• fasted (post absorptive) state (body needs to draw upon its fuel stores)

Question 2

what is the state of metabolism in the fed state

Answer 2

anabolic
-Nutrient molecules are used to provide energy stores or to
provide needs of growth and maintenance of cells and tissues
-But these needs mean that some molecules are used immediately
to provide energy

Question 3

what is the state of metabolism in the fasted state

Answer 3

catabolic

-The body calls on the energy stores, so they become depleted

Question 4

what determines the rate of different metabolic pathways

Answer 4

concentrations of substrates and products (direct or down- stream) of reactions determine their rate as does the activity of the relevant enzymes

Question 5

What are the key hormones in regulating metabolism

Answer 5

Insulin
Glucose
Adrenaline and noradrenaline

Question 6

What are the actions of these hormones mediated by

Answer 6

activation of intracellular protein kinases and phosphorylation of key regulatory proteins on tyrosine, serine or threonine residues – covalent modifications alter enzyme activities

Question 7

is the majority of the pancreas’s function

Answer 7

exocrine function (digestive enzymes)

Question 8

What factors drive the fed state

Answer 8

1. Stimulates glycogen synthesis in liver and muscle
2. Stimulates uptake of glucose into muscle and adipose tissue
3. Stimulates glycolysis and hence fatty acid synthesis in liver
4. Stimulates formation of triglycerides in fat tissue
5. Stimulates protein synthesis in muscle

Question 9

Actions of glucagon

Answer 9

alpha cells in the pancreas release it when glucose blood levels fall during the fasting stat e
what are its targets in the liver:
1. Stimulates release of glucose from glycogen
2. Stimulates gluconeogenesis but inhibits glucose incorporation into glycogen
Stimulates breakdown of triglycerides in fat tissue

Question 10

What determines whether metabolism is in the fed or fasting state

Answer 10

the balance between circulating levels of insulin and glucagon

Question 11

What secretes adrenaline and noradrenaline

Answer 11

the adrenal medulla and neurones of the sympathetic nervous system when blood glucose conc falls

Question 12

what are the actions of adrenaline and noradrenaline

Answer 12

• they drive breakdown of glycogen and triglycerides
• their glycogenolytic action is mainly on muscle (producing glucose-6-P) rather than on liver
• The amines lower glucose uptake by muscle, so that fatty acids released by adipose tissue are used as fuel
• The amines also increase glucagon secretion and inhibit insulin secretion

Question 13

what is blood glucose before and after a meal

Answer 13

80 mg/100 ml before

120 mg/100 ml after

Question 14

what indicates hypoglycaemia

Answer 14

Lowered blood [glucose] (<3 mmol/litre)

Question 15

What indicates hyperglycaemia

Answer 15

Elevated blood [glucose] (>11 mmol/litre)

Question 16

How long can body fuel stores last

Answer 16

about 1-3 months of starvation, depending on level of physical activity
carb stores only a day or less (BG falls)

Question 17

what is important to remember about triglycerides

Answer 17

have a limited ability to be converted to glucose

Question 18

What happens during the first days of starvation

Answer 18

-Proteins potentially can yield glucose (gluconeogenesis), but these
need to be preserved as much as possible
- Muscle shifts from its use of glucose as a fuel to using fatty acids
released from adipose tissue (so sparing glucose for the brain)
- The liver uses fats mobilized from adipose tissue and pyruvate, lactate and alanine (from breakdown of protein) from muscle to make as much glucose as possible for export into the blood (for the brain)

Question 19

What happens during the later days of starvation

Answer 19

After about 3 days large amounts of ketone bodies begin to be formed by the liver (as a consequence of breaking down fatty acids and limitations in the activity of the TCA cycle)
HOWEVER
Over the first few days of fasting the brain becomes more tolerant of lowered blood [glucose] and gains the ability to use ketone bodies to meet some of its fuel requirements.
- because the body uses less glucose, the need for amino acids to fuel gluconeogenesis is also reduced so there is a reduction in the rate at which muscle is broken down

Question 20

What is the most common metabolic disease

Answer 20

Diabetes mellitus indicated by sugar in the urine

Question 21

What are the two types of diabetes

Answer 21

Type 1 (insulin-dependent = juvenile onset) autoimmune where the beta cells of the pancreas are destroyed so little insulin can be secreted

Type 2 (non-insulin-dependent = insulin-resistant
= adult onset) associated lifestyle (little exercise, ready access to food and obesity), and there can be a genetic component
-Tissues are insensitive to the effects of insulin.

Question 22

Effects of diabetes mellitus

Answer 22

• metabolism is largely similar to that seen during prolonged fasting
  1. Glycolysis is slowed
  2. Gluconeogenesis (new glucose) is stimulated (using amino acids produced by protein breakdown)
  3. Fatty acids (from adipose tissue) are broken down and used to form ketone bodies
  4. Newly formed glucose and ketone bodies pass into the blood

Question 23

Why is diabetes associated with excessive urination

Answer 23

1. In the glomeruli of the kidney glucose leaves the blood and passes into the urine along with ions and other relatively small molecules
2. Normally
   transporters in the proximal convoluted tubule reabsorb all the glucose and return it to the blood
3. In diabetes if the blood [glucose] rises beyond a certain level, the amount that passes into the kidney tubules is so great that the transporters cannot remove it all
4. This glucose adds to the osmotic strength of the urine
5. This makes it harder for the kidney to reabsorb water from the
   urine
6. The result is that the urine volume is greatly increased
   -It also explains why the urine of a diabetic contains glucose
7. In severe cases, acidic ketone bodies also appear in the urine (ketoacidosis) adding slightly to the osmotic strength.
   -It also explains why the urine of a diabetic contains ketones

Question 24

What damage can diabetes mellitus do long term if untreated

Answer 24

• Blood vessels (polyneuropathy)
• Eyes (Retinal blood vessels)
• Kidneys (urine infection; scarring and swelling in glomeruli leading to appearance of protein in the urine)
• Cardiovascular disease (largely a result of narrowing of blood vessels)
• Ketone bodies cause acidosis, which cannot be fully counteracted
  As a result, an individual with uncontrolled diabetes can go into a coma as a result of low blood pH coupled with dehydration