Endocrine control and metabolism Flashcards
State which process is at the core of energy metabolism?
“TCA cycle
FC:
- From TCA, ATP can be produced via ETC chain”
What is the central molecule in energy metabolism and why?
“Acetyl coA
- Any molecule that can be metabolized to Acetyl CoA
can be fed into the TCA.
- From TCA, ATP can be produced “
Name 5 examples of circulating nutrients?
“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”
Name 3 examples of stored nutrients?
“Glycogen
Triglycerides (TG, TAG)
Body proteins
“
State what concentration plasma glucose is kept constant at?
5 mmol L-1
Which metabolised nutrient does the brain depend on?
Metabolism of glucose
State critical range for hypoglycemia and its effects
” - ultimately coma and death
”
State what hyperglycemia is and its effects
“chronic exposure to raised glucose concentrations leads to protein damage via non-enzymatic glycation
- Glycation = addition of carb to protein
“
Why must glucose be constantly replensished?
“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”
State two sources of plasma glucose?
“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”
“What prevents plasma glucose surging after a meal and
plummeting between meals?
“
“Hormones regulate the integration of carbohydrate, fat and protein metabolism to maintain constant plasma glucose levels.
“
State the two phases of metabolism and define them?
“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)
“
State the hormones which regulate metabolic pathways?
“Insulin
Counter-regulatory hormones
These promote energy storage or release
“
State the role of insulin in regulation of metabolic pathways?
“Signal of the fed state:
Promotes storage of nutrients/ Inhibits nutrient release
Decreases plasma glucose
“
“State the role of counter-regulatory hormones and state 4
examples?”
“Role (when plasma glucose falls)
- Promote nutrient release (for fuel)
- Raises plasma glucose
Examples
Glucagon
Adrenaline (epinephrine)
Cortisol
Growth hormone (somatotrophin)
“
”
State how insulin stimulates nutrient storage?”
”- Uptake of glucose by skeletal muscle, adipose and other tissues
- Glycogen synthesis in liver, skeletal muscle,
- Uptake of FA and amino acids
“
State how insulin inhibits nutrient release?
”- Inhibits release of glucose from liver (hepatic glucose production)
- Inhibits fat and protein breakdown (lipolysis and proteolysis)
“
State effect of glucagon in terms of counter-regulatory hormones?
Principal effects in liver (hepatic)
Stimulates hepatic glucose production
“
State effect of adrenaline in terms of counter-regulatory hormones?
“Adrenaline via sympathetic NS)
Stimulates hepatic (liver) glucose production
Stimulates lipolysis: release of FA from adipose tissue stores
“
State effect of growth hormone in terms of counter-regulatory hormones?
“Stimulates hepatic (liver) glucose production, lipolysis ( release of FA from adipose tissue stores)
“
State effect of cortisol in terms of counter-regulatory hormones?
“Stimulates hepatic glucose production,
lipolysis (release of FA from adipose tissue)
Stimulates proteolysis: release of amino acids from body proteins (skeletal muscle)
“
“State the metabolic pathways which are involved in energy storage and link
them?”
“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
“
State the metabolic pathways involved in energy release and link them?
“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
“
Draw or describe the feedback system in the metabolic response to hypogylcemia?
“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.
“
State the short-term defences against hypoglycaemia?
“Glucagon
Epinephrine
Sympathetic NS
These directly increase hepatic (liver) glucose production
“
State the medium-term defences against hypoglycaemia?
“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
“
State the long-term defences against hypoglycaemia?
“Cortisol stimulates proteolysis to supply amino acid substrates for gluconeogenesis
“
State the action of insulin in the defence against hyperglyceamia?
“Stimulates glucose uptake by tissues
Inhibits hepatic glucose production
“
What would occur if a lack of insulin action occured?
“hyperglycaemia -> diabetes mellitus
“
State the 2 types of diabetes millitus with cause?
“Type 1 DM: insulin deficiency
Type 2 DM: insulin insufficiency combined with insulin resistance
“
State the 3 major insulin sensitive tissues?
“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
“
State the possible fates of glucose? (4)
“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.
“
State pathways in adipose tissue for glucose?
“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.
”
State pathways in muscle for glucose?
“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
“
State glucose and AA metabolism within the liver?
“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.
“
Describe FA metabolism within the liver?
“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).
“
Diabeteic ketoacidosis? LO
“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.
“
