1 - endocrine Flashcards

Question

describe how glycogenolysis occurs in MUSCLE via the adenylate cyclase/cAMP/PKA pathway

Answer 1

1. adrenaline binds to adrenoreceptor on myocyte 2. Gs proteins stimulate adenylate cyclase 3. AMP —> cAMP 4. activates PKA 5. PKA phosphorylates PK 6. PK phosphorylates glycogen phosphorylase (GP) 7. active GP catalyses breakdown of glycogen to G1P 8. G1P converted to G6P 9. G6P not converted to glucose, but is oxidised via glycolysis into pyruvate —> ATP ---> energy for local use

Answer 2

1. adrenaline binds to adrenoreceptor on adipocyte 2. Gs proteins stimulate adenylate cyclase 3. AMP —> cAMP 4. cAMP activates hormone-sensitive lipase (HSL) 5. HSL releases stored TAGs via hydrolysis to give fatty acids and glycerol 4. fatty acids transported to liver and muscle

Answer 3

excessive breakdown of fats occurs during states of fasting FA converted to acyl CoA, which is then beta-oxidised to acetyl CoA more acetyl CoA than citric acid cycle can handle not enough oxaloacetate* to combine with excess acetyl CoA excess acetyl coA forms ketone bodies * large amount of glyconeogenesis occurring to keep blood glucose levels normal —> oxaloacetate used as a substrate —> oxaloacetate deficient ketone bodies circulate to be used as an energy source

Answer 4

2 carbons oxidised at once yields ATP and acetyl CoA occurs in mitrochondria of liver fatty acids beta-oxidised in fasting states

Answer 5

2 acetyl-CoA molecules combine to give acetoacetate (ketone body) + H+ + other products acetoacetate is either: - reduced to beta-hydroxybutyrate - decarboxylated to give acetone ^ both ketone bodies this pathway is irreversible

Answer 6

1) fatty acids transported into cytoplasm 2) FAs react with CoA and carnitine 3) transported into mitochondria 4) beta-oxidised to yield ATP and acetyl CoA

Answer 7

ketone bodies: - acetoacetate - b-hydroxybutyrate - acetone

Answer 8

ketogenesis occurs during prolonged fasting, low carb diet, type 2 diabetes FA converted to acyl CoA —> acetyl CoA, which enters citric acid cycle (CAC) oxaloacetate + acetyl coA = citrate very low blood glucose —> large amount of gluconeogenesis occurring to keep blood glucose levels normal —> oxaloacetate used as a substrate not enough oxaloacetate to combine with excess acetyl CoA ``` excess acetyl coA forms ketone bodies: - acetoacetate - b-hydroxybutyrate - acetone these ketone bodies are produced in the liver and enter circulation, used as energy source ```

Answer 9

located over trachea gland is highly vascularised made of left and right lobe lobes contain many follicles (ring of follicular cells surrounding cholloid) cholloid contains ECF and stores thyroid hormones c-cells are located between follicles and produce calcitonin to ↓ calcium levels

Answer 10

Thyroxine (T4) = predominant form in plasma Triiodothyronine (T3) = most biologically active form Reverse T3 = Inactive form

Answer 11

hypothalamus releases TRH down pituitary stalk TRH crosses into interstitial space and binds to GPCRs on thyrotroph in anterior pituitary GPCR uses Gq —> phospholipase C —> calcium release —> exocytosis of TSH TSH goes into circulation and binds to receptors on follicular cells of thyroid gland synthesis and secretion of thyroid hormone (T3 and T4) from thyroid gland these hormones regulates basal O2 use and metabolism and consequent heat production

Answer 12

no, only iodine is essential in diet low iodine —> low thyroid hormone —> low metabolic rate 1) uptake and concentration of iodide (I-) 2) incorporation of I- into phenol ring of tyrosine 3) coupling of two iodinated tyrosine molecules to form T4 or T3

Answer 13

TG = large molecule with MIT, DIT, T3 + T4 residues TG comes from follicular cell via normal production of any protein (amino acids, transcription, translation, packed into vesicles and secreted into lumen through apical membrane) iodide transported into follicular cell on basal membrane (active transport - Na/I transporter), known as iodide “trapping” mechanism iodide exported through apical membrane into lumen iodide added to TG in lumen molecule taken into cholloid via pinocytosis (i.e. no receptor) thyroid hormones released from molecule via association with lysosome and diffuse out of follicular cell via basal membrane some MIT and DIT residues are recycled – iodide cleaved out and recycled – efficient mechanism ∴ can go for a sufficient period of time without ingesting iodine from diet

Answer 14

>99% circulating thyroid hormones are bound to plasma proteins e.g. TBG “free” fraction of THs is important, that that is the portion available to bind to receptors

Answer 15

slow, up to days

Answer 16

1) THERMOGENIC EFFECT – stimulates O2 consumption in most cells = heat production 2) GROWTH AND DEVELOPMENT – essential normal somatic growth and neural development – myelination of axons 3) METABOLISM – multifaceted – in general increase favours catabolism 4) CARDIOVASCULAR – increases response to catecholamines – enhances beta-adreno receptor responses 5) SKELETAL MUSCLE – abnormal levels = muscle weakness

Answer 17

HYPERTHYROID: basal metabolic rate: ↑ carbohydrate metabolism: ↑ gluconeogenesis, glycogenolysis. normal glucose protein metabolism: ↑ synthesis, proteolysis, muscle wasting lipid metabolism: ↑ lipogenesis + lipolysis, ↓ cholesterol thermogenesis: ↑ autonomic nervous system: ↑ expression of beta-adrenoreceptors HYPOTHYROID: basal metabolic rate: ↓ carbohydrate metabolism: ↓ gluconeogenesis, glycogenolysis. normal glucose protein metabolism: ↓ synthesis, proteolysis lipid metabolism: ↓ lipogenesis + lipolysis, ↑ cholesterol thermogenesis: ↓ autonomic nervous system: normal

Answer 18

normal levels free TH

Answer 19

hypothyroidism = deficiency of TH secretion (T4 in particular) causes: • immune system attacks follicular cells —> cannot produce hormones • failure of gland (Hashimoto’s autoimmune thyroiditis) • secondary to deficiency TRH, TSH • inadequate supply of iodine ``` symptoms: • reduced basal metabolic rate poor resistance to cold • excessive weight gain • easily fatigued • slow weak pulse • slow mentation & reflexes ``` myxoedema: • oedema of skin and tissues • "tragic facial expression" cretinism: • hypothyroidism since birth • usually iodine deficiency • mental retardation, small stature, low MR, sexual immaturity

Answer 20

thyroxine therapy: thyroxine converted to T4 iodine administration

Answer 21

hypothyroidism = overproduction of TH (thyrotoxicosis) causes: • graves disease (autoimmune - production of antibodies that act like TSH) • excess TRH or TSH (result from tumour in hypothalamus or in thyrotrophs of pituitary) • hypersecreting thyroid tumour (most common) symptoms: • elevated basal metabolic rate • excessive sweating & heat intolerance • weight loss despite increase appetite • muscle weakening (tremor) • excessively alert, irritable, anxious, emotional • heart palpitations • bulging eyes (orbital muscles have TH receptors - common in graves disease)

Answer 22

goitre = enlargement of the thyroid gland OCCURS WHEN THERE IS INCREASED TSH – TSH drives cell division and hypertrophy of follicular cells can occur in hypothyroid OR hyperthyroid states hypothyroid: deficient in thyroid hormone = reduced long loop negative feedback = release TSH to stimulate synthesis and secretion of thyroid hormone hyperthyroid: tumour in hypothalamus or in thyrotrophs of pituitary results in excess TSH goitres commonly results from iodine deficiency and graves disease

Answer 23

adrenal gland consists of adrenal cortex and medulla adrenal cortex (80%): - zona glomerulosa (outermost) - zona faciculata - zona reticularis (innermost) cortex produces steroid hormones (e.g. cortisol)

Answer 24

• gonadal or sex steroids e.g. progesterone, testosterone, oestradiol • glucocorticoids e.g. cortisol, corticosterone • mineralocorticoids e.g. aldosterone

Answer 25

HPA axis becomes activated under stress hypothalamus releases CRH CRH travels down pituitary stalk to ant. pituitary ant. pituitary release ACTH into circulation ACTH binds to receptor on adrenal cortex and signals through cAMP near term: • increases cholesterol transport into mitochondria • increases cholesterol binding to P450 side-chain cleaving enzyme (rate-limiting) —> increase pregnenolone (precursor) medium term: • increase gene transcription of side-chain cleaving enzyme • increases transcription of LDL receptor long term: • trophic to cell (size and number) • enhances functionality of organelles adrenal cortex releases cortisol into circulation where it acts on target cells

Answer 26

FALSE ACTH levels are not regulated by circadian clock ACTH levels normal but cortisol IS INCREASED in the morning the circadian clock enhances the response of the adrenal gland in the morning

Answer 27

1) FUEL METABOLISM: • in peripheral tissues, cortisol is catabolism: –– stimulates lipolysis in adipocytes to mobilise FA → used for energy –– in muscle, decrease AA uptake (oppose insulin) • in liver, cortisol is anabolic: –– stimulates gluconeogenesis –– increase glucose and AA storage (↑ glycogen + protein) 2) PERMISSIVE EFFECTS: • metabolic reactions & vascular reactivity 3) WATER METABOLISM • necessary for normal water excretion 4) RESISTANCE ADAPTION TO STRESS • preserves blood glucose 5) NERVOUS SYSTEM • regulates mood and behaviour 6) REDUCE RESPONSE TO INFLAMMATORY STIMULI AND IMMUNOSUPPRESSION

Answer 28

addison's disease is chronic failure of the adrenal cortex causes: • autoimmune • no ACTH • adrenalectomy symptoms: • loss of gluccocorticoids = reduction in stress response and metabolism abnomalities (hypoglycemia) • loss of aldosterone = massive electrolyte imbalance, dehydration and hypotension FATAL IF UNTREATED

Answer 29

cuchsing's syndrome is an excess of gluccocorticoids causes: • very rare ACTH secreting tumour • adrenal tumour (hypersecrete cortisol) • over-medication with anti-inflammatory steroids ``` symptoms: • extra gluccocorticoids have catabolic effects • protein depletion • immune deficiency • thin skin and hair • body fat redistributed (obesity) • insulin-resistant diabetes ```

Answer 30

hormones which control early maturation before ovaries/testes have fully matured synthesis of adrenal androgens is regulated by ACTH very important: • in fetus • during childhood in both sexes “adrenarche” • in females throughout life • in adult males, not so important due to excess gonadal androgens high levels leads to: • precocious pseudopuberty in males • pseudohermaphroditism in females

Answer 31

in child, GH causes true growth and has metabolic effects in adults, GH maintains muscle mass and retains same metabolic functions ``` muscle: • ↑ AA uptake • ↓ glucose uptake • ↓ protein breakdown • ↑ muscle mass ``` adipose tissue: • ↓ glucose uptake • ↑ fat breakdown liver: • ↑ protein synthesis • ↑ gluconeogenesis

Answer 32

GH signals through JAK/STAT pathway 1) GH binds and receptor dimerises 2) JAK molecules phosphorylate each other 3) active JAK molecules phosphorylate receptor to create SH2 binding domains 4) STAT molecules bind to SH2 domain 5) JAK phosphorylates STAT 6) STAT molecules disassociate and dimerise 7) STAT dimer translocates to nucleus to induce transcription of target proteins

Answer 33

GH is the only “anabolic hormone” to increase during fasting (insulin and IGF-I levels decrease) Catabolic hormones increase (glucagon, adrenaline and cortisol) GH works to preserve muscle mass

Answer 34

GH stimulates of lipolysis (FA as energy source) protein and glucose metabolism remain unaffected

Answer 35

1) immediate • power events • ADP and phosphocreatine generate ATP ``` 2) oxidative • sprints • anaerobic glycolysis • glycogenolysis provides glucose • fastest pathway ``` 3) non-oxidative • >2 mins • oxidation of fat and glucose • most efficient pathway

Answer 36

``` ↑ adrenaline ↑ glucagon ↑ cortisol ↑ GH ↓ insulin ``` Glucose decreases but doesn’t deplete Glycerol and free fatty acids increased – you start mobilising fat reserves which are used to produce energy Glycerol required for gluconeogenesis

Answer 37

reduced glucose uptake + no exercise = less trafficking low insulin, increased glucagon, increased GH reduced glucose uptake in skeletal muscle and adipose tissue shift to FA oxidation increased: • glycogenolysis • gluconeogenesis • lipolysis

Answer 38

shift from enhanced gluconeogenesis of protein stores to ketogenesis from fat ketone bodies used as fuel for brain, muscle and other tissues stress response: ↓ insulin, thyroxine ↑ glucagon, adrenalin, cortisol, GH liver becomes site for gluconeogenesis kidney becomes site for ketogenesis —> uses various aa’s as precursors for glucose eventually, ketone bodies converted back into acetyl CoA – decrease gluconeogenesis in liver – enhanced gluconeogenesis in kidney – increased ketogenesis in liver

Answer 39

lactate is produced in the muscle fibres during contraction and afterwards is released into circulation where it is taken up by the liver and used to produce glucose in gluconeogenesis

Answer 40

1. Maintain blood glucose for brain function – CNS main energy source – Other tissues are capable of oxidation of FAs 2. Maintain protein reserves – Contractile proteins, enzymes, nervous tissue