8. Hormonal water salt balance

In signal transduction, what is the specific role of 'amplifier proteins'?

They significantly increase the signal strength, often via a signal cascade involving enzymes or ion channels.

Which type of intracellular protein connects one signaling protein to another without possessing its own enzymatic activity?

Adaptor proteins.

How do 'integrator proteins' process incoming information within a cell?

They receive signals from two or more pathways and integrate them before further transmission.

What defines the function of 'latent gene-regulatory proteins' following activation by surface receptors?

They migrate to the nucleus to stimulate gene transcription.

G protein–coupled receptors (GPCRs) are characterised by having _____ transmembrane \alpha-helices.

7

During GPCR activation, the G protein becomes active when the \alpha-subunit binds to _____.

GTP

In the TGF-\beta signaling pathway, which specific Smad protein acts as a common partner required for translocation to the nucleus?

Smad4

Which Smad proteins serve as inhibitors of the TGF-\beta signaling pathway?

Smad6 and Smad7.

In the JAK-STAT signaling pathway, what is the immediate consequence of cytokine binding to the receptor?

Receptor dimerisation.

Which secondary mediator is responsible for inducing Ca^{2+} release from the endoplasmic reticulum?

Inositol 1,4,5-trisphosphate (IP_3).

How does the regulation of soluble adenylate cyclase differ from transmembrane adenylate cyclases?

Soluble adenylate cyclase is activated by bicarbonate and calcium ions rather than G proteins.

What is the structural composition of inactive Protein Kinase A (PKA)?

A tetramer consisting of 2 regulatory subunits and 2 catalytic subunits.

In the cAMP-dependent pathway, which nuclear protein is phosphorylated by PKA to regulate transcription?

CREB (cAMP response element binding protein).

Which secondary mediator activates Protein Kinase C (PKC)?

Diacylglycerol (DAG).

Nitric oxide (NO) triggers signal transduction by activating which specific enzyme in neighboring cells?

Soluble guanylate cyclase (sGC).

What is the approximate concentration of free cytosolic Ca^{2+} in a resting cell?

0.1 \mu mol/L

Which enzyme converts ATP into cAMP in the plasma membrane?

Adenylate cyclase.

Which lipid mediator is generated by the action of Sphingomyelinase on sphingomyelin?

Ceramide.

Phospholipase C (PLC) acts on the substrate PIP_2 to produce which two secondary mediators?

Diacylglycerol and Inositol-3-phosphate.

Which enzyme is responsible for the conversion of L-arginine into nitric oxide and L-citrulline?

Nitric oxide synthase (NOS).

Thyroid hormones are considered lipophilic, meaning they travel through the blood bound to proteins like albumin and _____.

TBG (thyroid-binding globulin).

What is the approximate percentage of T_4 that exists in the free, biologically active form?

0.02\%

Which type of deiodinase is primarily responsible for maintaining intracellular T_3 levels and increases its activity during hypothyroidism?

Type 2 Deiodinase (D2).

What is the primary role of Type 3 Deiodinase (D3) in thyroid hormone metabolism?

It inactivates T_4 and T_3 by producing reverse T_3 (rT_3).

The non-genomic effects of thyroid hormones are mediated by membrane receptors such as _____.

Integrin \alpha v \beta 3

Which enzyme catalyzes the rate-limiting step of catecholamine synthesis?

Tyrosine hydroxylase (TH).

The adrenal medulla is considered a modified sympathetic ganglion that primarily secretes _____.

Epinephrine (Adrenaline).

Which enzyme converts Norepinephrine into Epinephrine in the adrenal medulla?

Phenylethanolamine-N-methyltransferase (PNMT).

Activation of \alpha 1-adrenergic receptors leads to the stimulation of which signaling enzyme?

Phospholipase C (PLC).

How do \alpha 2-adrenergic receptors influence cAMP levels within the cell?

They are coupled to Gi proteins which inhibit adenylate cyclase, leading to decreased cAMP.

All \beta-adrenergic receptors are coupled to which type of G protein?

Gs protein.

In the liver, adrenaline stimulates the breakdown of glycogen, a process known as _____.

Glycogenolysis

What effect does adrenaline have on insulin secretion through \alpha-adrenergic receptors?

It inhibits insulin secretion.

During heart failure, high adrenaline levels lead to the inhibition of which mitochondrial enzyme complex, shifting metabolism toward anaerobic glycolysis?

Pyruvate Dehydrogenase (PDH).

Which clinical marker is used to assess endogenous insulin secretion because it is released in equimolar amounts with insulin?

C-peptide.

Tirzepatide is a dual agonist for which two gastrointestinal peptide receptors?

GIP and GLP-1.

The conversion of testosterone to the more potent dihydrotestosterone (DHT) is catalysed by the enzyme _____.

5-alpha-reductase

Which enzyme converts testosterone into estradiol in adipose tissue and the brain?

Aromatase (CYP19).

What is the common precursor for the synthesis of all classes of steroid hormones?

Cholesterol.

In the adrenal cortex, which enzyme converts 11-deoxycortisol into cortisol?

11-beta-hydroxylase (CYP11B1).

What triggers the hyperpigmentation seen in Addison's disease?

Decreased cortisol leads to increased ACTH and MSH production from Proopiomelanocortin (POMC).

Nuclear receptors are typically bound to which proteins in the cytoplasm while in their inactive state?

Heat shock proteins (HSPs).

Which nuclear receptor functions as a 'cholesterol sensor' and protects against atherosclerosis?

Liver X receptor (LXR).

Which isoform of PPAR is predominantly found in adipose tissue and regulates adipogenesis and insulin sensitivity?

PPAR-gamma.

Thiazolidinediones (TZDs) are therapeutic ligands that act as agonists for which nuclear receptor?

PPAR-gamma.

In Phase I biotransformation of carcinogens, which enzyme system is primarily involved in hydroxylation reactions?

Cytochrome P450 (monooxygenases).

What is the primary goal of Phase II biotransformation (conjugation) of metabolic products?

To increase polarity and facilitate excretion via urine.

Mutated KRAS leads to abnormal cell growth by maintaining signaling through the MAPK pathway even when which upstream receptor is inhibited?

EGFR (Epidermal Growth Factor Receptor).

What are the three main signaling pathways activated by Platelet-Derived Growth Factor (PDGF)?

RAS-MAPK, PI3K-AKT, and PLC-gamma.

Which enzyme converts ATP to cAMP in the context of G-protein coupled receptors?

Adenylate cyclase.

What is the primary function of the Renin-Angiotensin-Aldosterone System (RAAS)?

Regulation of arterial blood pressure and water-salt balance.

What specific stimuli trigger the release of renin from juxtaglomerular cells?

Decreased blood pressure or decreased renal perfusion.

Which enzyme is responsible for converting Angiotensin I into the potent vasoconstrictor Angiotensin II?

Angiotensin converting enzyme (ACE).

Angiotensin I is a decapeptide, whereas Angiotensin II is an _____.

octapeptide

Through which signaling pathway does Angiotensin II act to stimulate aldosterone secretion in the zona glomerulosa?

The Gq-PLC-IP3/Calcium-PKC pathway.

What is the main physiological effect of aldosterone on the kidneys?

It increases sodium and water reabsorption while increasing potassium excretion.

What is the primary stimulus for the release of Atrial Natriuretic Peptide (ANP)?

Increased blood volume leading to atrial stretching.

Where is Brain Natriuretic Peptide (BNP) primarily synthesized and secreted from?

The cardiac ventricles.

What is the structural commonality between ANP, BNP, and CNP?

They contain a 17-amino acid ring structure formed by a disulfide bridge.

Which natriuretic peptide receptor lacks guanylyl cyclase activity and functions mainly as a clearance receptor?

NPR-C.

What is the cellular second messenger produced when natriuretic peptides bind to NPR-A or NPR-B receptors?

cGMP (cyclic guanosine monophosphate).

Parathyroid hormone (PTH) acts on the kidneys to increase the reabsorption of calcium and decrease the reabsorption of _____.

phosphate

How does Parathyroid hormone (PTH) influence calcium levels via the intestines?

It stimulates the synthesis of calcitriol, which increases intestinal calcium absorption.

Which hormone is the functional antagonist to the Renin-Angiotensin-Aldosterone System in regulating blood volume?

ANP (Atrial Natriuretic Peptide) or BNP.

Where is C-type Natriuretic Peptide (CNP) primarily produced, and what is its typical mode of action?

It is produced in the brain and endothelium, acting mainly as a local regulator.

What is the effect of Atrial Natriuretic Peptide on the release of renin?

It inhibits the release of renin.

What effect does Angiotensin II have on systemic vascular resistance?

It causes potent vasoconstriction, increasing systemic vascular resistance.

Which hormone is secreted by the thyroid gland to lower blood calcium levels by inhibiting bone resorption?

Calcitonin.

What is the relationship between the genes for Parathyroid Hormone (PTH) and Parathyroid Hormone-related Protein (PTHrP)?

They are encoded by different genes despite their similar names and receptor binding.

The clinical condition characterised by hypertension and suppressed renin due to an aldosterone-secreting tumor is called _____ syndrome.

Conn's

Which enzyme converts angiotensinogen into Angiotensin I?

Renin.

What occurs to GFR (Glomerular Filtration Rate) in response to ANP and BNP activity?

GFR increases.

Which molecule is the main precursor for the synthesis of adrenaline in the sympathetic nervous system?

Tyrosine.

What is the metabolic 'vicious circle' described in heart failure concerning fatty acids?

High adrenaline increases free fatty acids, which inhibit mitochondrial ATP synthesis and pyruvate entry into the TCA cycle.

Which secondary mediator activates Protein Kinase G (PKG)?

cGMP.

The process where a signal is converted into another form, such as adenylate cyclase forming cAMP, is known as _____.

transduction

Which Smad proteins transmit the signal directly from the TGF-beta receptor?

Smad2 and Smad3.

What is the physiological role of reverse T3 (rT3)?

It is a biologically inactive metabolite of T4.

In the synthesis of thyroid hormones, which enzyme catalyzes the oxidation and iodination of tyrosine residues on thyroglobulin?

Thyroid peroxidase (TPO).

Which steroidogenic enzyme is specific to the zona glomerulosa for the production of aldosterone?

Aldosterone synthase (CYP11B2).

Which glucose transporter's expression is increased by PPAR-gamma agonists in adipocytes?

GLUT4.

The 'Warburg effect' in cancer cells refers to the reprogramming of metabolism towards _____.

aerobic glycolysis

In the resting state, NF-kappaB is kept inactive in the cytoplasm by being bound to _____.

IkB

What is the primary role of the Retinoid X Receptor (RXR) in nuclear receptor signaling?

It acts as a common heterodimerisation partner for many other nuclear receptors like LXR, FXR, and PPAR.

Which catecholamine metabolite is measured in urine to diagnose pheochromocytoma?

VMA (vanillylmandelic acid).