Endocrine control and metabolism

Question 1

State which process is at the core of energy metabolism?

Answer 1

“TCA cycle

FC:
- From TCA, ATP can be produced via ETC chain”

Question 2

What is the central molecule in energy metabolism and why?

Answer 2

“Acetyl coA
- Any molecule that can be metabolized to Acetyl CoA
can be fed into the TCA.
- From TCA, ATP can be produced “

Question 3

Name 5 examples of circulating nutrients?

Answer 3

“Circulating= Immediately availiable for energy metabolism

• Glucose
• Fatty acids (FA, FFA, NEFA)
• Amino acids

Originate from metabolic processes:

• Ketone bodies
• Lactate

NEFA= Non-esterified fatty acids”

Question 4

Name 3 examples of stored nutrients?

Answer 4

“Glycogen
Triglycerides (TG, TAG)
Body proteins
“

Question 5

State what concentration plasma glucose is kept constant at?

Answer 5

5 mmol L-1

Question 6

Which metabolised nutrient does the brain depend on?

Answer 6

Metabolism of glucose

Question 7

State critical range for hypoglycemia and its effects

Answer 7

” - ultimately coma and death

”

Question 8

State what hyperglycemia is and its effects

Answer 8

“chronic exposure to raised glucose concentrations leads to protein damage via non-enzymatic glycation
- Glycation = addition of carb to protein
“

Question 9

Why must glucose be constantly replensished?

Answer 9

“Majority of glucose is predominantly held in the ECF (40% of body weight / 2/3/ of water)
- Held at constant 5 mmoL-1

ICF has impermeable membranes to solutes like glucose

• But can be uptaken via transport
• When it does, it is immediately metabolised.

Different organs have different rate of glucose consumption e.g.
Brain: ~ 30 mmol hr -1 ,
Skeletal muscle:
~ 300 mmol hr -

So glucose will last minutes to couple of hours at max due to quick consuption from organs”

Question 10

State two sources of plasma glucose?

Answer 10

“Diet (Up to 3000 mmol day-1)
Organs that can export glucose into the circulation
e..g liver.

FC: Liver can store or synthesise glucose from different forms”

Question 11

“What prevents plasma glucose surging after a meal and
plummeting between meals?
“

Answer 11

“Hormones regulate the integration of carbohydrate, fat and protein metabolism to maintain constant plasma glucose levels.
“

Question 12

State the two phases of metabolism and define them?

Answer 12

“Absorptive and fasting

Storage of nutrients in the absorptive phase (fed state)
Release of nutrients in the fasting phase (between meals, also called postabsorptive phase)
“

Question 13

State the hormones which regulate metabolic pathways?

Answer 13

“Insulin
Counter-regulatory hormones

These promote energy storage or release
“

Question 14

State the role of insulin in regulation of metabolic pathways?

Answer 14

“Signal of the fed state:
Promotes storage of nutrients/ Inhibits nutrient release
Decreases plasma glucose
“

Question 15

“State the role of counter-regulatory hormones and state 4
examples?”

Answer 15

“Role (when plasma glucose falls)

• Promote nutrient release (for fuel)
• Raises plasma glucose

Examples
Glucagon
Adrenaline (epinephrine)
Cortisol
Growth hormone (somatotrophin)
“

Question 16

”
State how insulin stimulates nutrient storage?”

Answer 16

”- Uptake of glucose by skeletal muscle, adipose and other tissues
- Glycogen synthesis in liver, skeletal muscle,
- Uptake of FA and amino acids
“

Question 17

State how insulin inhibits nutrient release?

Answer 17

”- Inhibits release of glucose from liver (hepatic glucose production)
- Inhibits fat and protein breakdown (lipolysis and proteolysis)
“

Question 18

State effect of glucagon in terms of counter-regulatory hormones?

Answer 18

Principal effects in liver (hepatic)
Stimulates hepatic glucose production
“

Question 19

State effect of adrenaline in terms of counter-regulatory hormones?

Answer 19

“Adrenaline via sympathetic NS)
Stimulates hepatic (liver) glucose production
Stimulates lipolysis: release of FA from adipose tissue stores
“

Question 20

State effect of growth hormone in terms of counter-regulatory hormones?

Answer 20

“Stimulates hepatic (liver) glucose production, lipolysis ( release of FA from adipose tissue stores)
“

Question 21

State effect of cortisol in terms of counter-regulatory hormones?

Answer 21

“Stimulates hepatic glucose production,
lipolysis (release of FA from adipose tissue)
Stimulates proteolysis: release of amino acids from body proteins (skeletal muscle)
“

Question 22

“State the metabolic pathways which are involved in energy storage and link
them?”

Answer 22

“1) Glycogenesis:
Synthesis of glycogen from glucose

When glycogen stores are full, they are converted to acteyl coA which then…

2) Enters Lipogenesis
Synthesis of FA from acetyl CoA
- Instead of FA being used for energy it is then…

3) Triglyceride synthesis
Esterification of FA for storage as TG

These pathways are stimulated as insulin
“

Question 23

State the metabolic pathways involved in energy release and link them?

Answer 23

“Direct increase of plasma glucose
1) Glycogenolysis
Release of glucose from glycogen stores
OR
2) Gluconeogenesis
De novo synthesis of glucose from non-carbohydrate substrates

Conserve plasma glucose by switiching to other metabolic fuels (these occur chronologically)

1) Lipolysis : Release of FA from TG breakdown
2) Beta-oxidation: FA to Acetyl Co A
3) Ketogenesis :Production of ketone bodies from Acetyl CoA -
- Ketone bodies are used as a parital substitute of fuel for glucose
“

Question 24

Draw or describe the feedback system in the metabolic response to hypogylcemia?

Answer 24

“DIAGRAM IS ANSWER. THIS IS FC.

The immediate response is glucagon release from the pancreas. The fall in plasma glucose is detected in the pancreas itself, and the response is to turn up the rate of glucagon secretion, from pancreatic endocrine cells called alpha cells, to be considered later. Glucose is also sensed in the brainstem and hypothalamus, where a fall increases sympathetic outflow, which directly and indirectly stimulates hepatic glucose output.

Note that this is a –ve fb system. If plasma glucose falls the responses are such as to raise it. If plasma glucose rises these responses would be inhibited, reducing hepatic glucose output.

Note also that the –ve fb involves endocrine, neural, and neuroendocrine reflex loops. Purely endocrine: pancreas senses falling glucose, increases glucagon secretion, which in turn increases hepatic glucose output. Neuroendocrine reflex involves glucose sensing by neurons, sympathetic output to adrenal stimulating adrenaline secretion.
“

Question 25

State the short-term defences against hypoglycaemia?

Answer 25

"Glucagon Epinephrine Sympathetic NS These directly increase hepatic (liver) glucose production "

Question 26

State the medium-term defences against hypoglycaemia?

Answer 26

"Ketogenesis: fat reserves can provides a partial substitute for glucose, - spares muscle tissue from the destruction that would otherwise be needed to provide amino acid substrates for gluconeogenesis "

Question 27

State the long-term defences against hypoglycaemia?

Answer 27

"Cortisol stimulates proteolysis to supply amino acid substrates for gluconeogenesis "

Question 28

State the action of insulin in the defence against hyperglyceamia?

Answer 28

"Stimulates glucose uptake by tissues Inhibits hepatic glucose production "

Question 29

What would occur if a lack of insulin action occured?

Answer 29

"hyperglycaemia -\> diabetes mellitus "

Question 30

State the 2 types of diabetes millitus with cause?

Answer 30

"Type 1 DM: insulin deficiency Type 2 DM: insulin insufficiency combined with insulin resistance "

Question 31

State the 3 major insulin sensitive tissues?

Answer 31

"Considering plasma glucose regulation these are: Liver (most important for controlling plasma glucose during fasting phase. ) Skeletal muscle (most important in buffering rise in plasma glucose Adipose tissue "

Question 32

State the possible fates of glucose? (4)

Answer 32

"1) Uptake. Via GLUT. This may be insulin-dependent (Glut4: muscle, adipose tissue) or insulin-independent, or constitutive (Glut1/2: liver, pancreas, brain, RBCs) 2) Energy; glycolysis, TCA 3) Beyond energy needs, glycogenesis 4) Glycogen stores full, lipogenesis. In liver, the FFAs formed from lipogenesis are esterified into TGs and packaged into lipoprotein particles (VLDLs) for export and storage in adipose tissue. "

Question 33

State pathways in adipose tissue for glucose?

Answer 33

"In times of positive energy balance: - insulin stimulates uptake lipoprotein lipase (LPL), GLUT4, hydrolyses TGs into FFAs, so they can enter the adipocyte. Then they are re-esterified to TGs for storage. - Glucose will diffuse into the adipocyte via the insulin-dependent GLUT4 channel. It’s then converted into FA via lipogenesis. In times of negative energy balance, counter-regulatory hormones (mainly adrenalin) stimulate lipolysis (breakdown of TG into FA) and release of FFA to circulation for uptake and energy metabolism. "

Question 34

State pathways in muscle for glucose?

Answer 34

"Can use glucose + FFA for energy Short term dependence on anaerobic respiration during intense work lactate production Lactate in circulation, used by liver for gluconeogenesis or oxidised Insulin = stimulates insertion of glucose transporters into membrane (GLUT4 = insulin dependent) Skeletal muscle is important is glucose buffering during absorptive phase = limiting rise in [glucose] in blood after a meal Glucose enters muscle and is converted to either glycogen or pyruvate, but muscle cannot make glucose-6-phosphate into glucose to be exported Glycogen made becomes the private source of energy for the tissu "

Question 35

State glucose and AA metabolism within the liver?

Answer 35

"with high insulin/low glucagon: Glucose metabolism is directed towards glycogen storage; when these are full glucose enters glycolysis and the resulting Acetyl CoA is fed into lipogenesis. With low insulin/high glucagon AAs are diverted away from protein synthesis into gluconeogenesis (multiple pathways for individual AAs, via pyruvate and/or TCA intermediates). A few AAs can be directly converted to Acetyl CoA (ketogenic AAs); these are fed into ketogenesis. "

Question 36

Describe FA metabolism within the liver?

Answer 36

"B oxidation. FA converted to fatty acyl-CoA, then acetyl CoA (in mitochondria – not shown). Acetyl CoA can be used to generate ATP via TCA. However, if in excess, acetyl CoA goes instead into ketogenesis as shown here. Glucose also converted to acetyl CoA. If in excess (of requirement for ATP generation) and in presence of insulin, acetyl CoA goes instead into lipogenesis, back to FAs (which will then be esterified to form TGs). The first intermediate in lipogenesis is malonyl CoA, which then goes through further intermediates to produce FAs. Malonyl CoA also has the effect of inhibiting CPT, which is required to get fatty acyl-CoA into mitochondria for oxidation (or ketogenesis). Thus, insulin indirectly inhibits B-oxidation. Insulin and glucagon thus partition FA metabolism between lipogenesis and TG synthesis. Stimulation of lipogenesis (insulin) prevents FA entry to mitochondria, inhibiting beta oxidation. In absence of insulin, acetyl CoA not converted to malonyl CoA, FA can enter mitochondria and Acetly CoA shuttled into ketogenesis. Importance of ketogenesis (synthesis of acetoacetate and hydroxybutyrate (ketone bodies) from Acetyl Co A). Ketone bodies exported from liver are freely transported in circulation, reconverted back to acetyl CoA, in brain and other tissues, and metabolised in TCA cycle for energy (thus sparing glucose). "

Question 37

Diabeteic ketoacidosis? LO

Answer 37

"DKA is an absence of insulin gluconeogenesis and beta oxidation are running unopposed. In the liver, oxidation of fatty acids and gluconeogenesis can compete for substrates Beta-oxidation of FA produces acetyl Co A, which combines with oxaloacetate (OAA) to form citrate, entering the TCA cycle for complete oxidative phosphorylation However, OAA is also used as a substrate in gluconeogenesis In absence of sufficient OAA, acetyl Co A builds up and is funnelled into ketogenesis Ketone bodies are acids: excess in circulation overwhelm buffering capacity of blood, leading to metabolic acidosis. "