Signal Transduction

What does signal transduction mean

The external hormone or neurotransmitter does not enter the cell but triggers a response by altering intracellular proteins to propagate and amplify the signal

What are the three types of G protein-coupled receptors (GPCRs)

Gs (stimulate adenylate cyclase)

What type of receptor does insulin bind to

Tyrosine kinase receptor with an intracellular catalytic domain

What do alpha- and beta-adrenoreceptors bind

Epinephrine and norepinephrine

How does the signal transduction system coordinate physiological responses

By GPCRs distributed throughout tissues responding primarily to sympathetic stimuli

What is the importance of specificity in ligand-receptor binding

It ensures efficient

What is upregulation in enzyme regulation

Increasing the number of working copies of an enzyme by enhancing synthesis

What is downregulation

Decreasing the number of enzyme copies by reducing synthesis or increasing degradation

What are allosteric effectors

Molecules that bind to enzymes at sites other than the active site to change enzyme activity

How does covalent modification regulate enzymes

By adding or removing groups such as phosphate to change enzyme function

What is the Michaelis-Menten model

Describes enzyme kinetics including affinity (Km) and maximum rate (Vmax)

What does a low Km mean

High affinity of enzyme for substrate

What does a high Km mean

Low affinity of enzyme for substrate

How does activation energy affect reaction rate

Increasing activation energy slows the reaction

Which amino acids commonly get phosphorylated

Tyrosine

What vitamins serve as coenzymes in enzyme reactions

Water soluble B vitamins and vitamin C

Which vitamin is converted to thiamine pyrophosphate (TPP)

Thiamine (B1)

Which vitamin produces FAD/FADH2 and FMN/FMNH2

Riboflavin (B2)

Which vitamin produces NAD+/NADH and NADP+/NADPH

Niacin (B3)

What coenzyme is derived from pyridoxine (B6)

Pyridoxal phosphate (PLP)

What coenzyme is derived from folic acid (B9)

Tetrahydrofolate (THF)

What coenzymes are derived from cobalamin (B12)

Methylcobalamin and 5'-deoxyadenosyl cobalamin

What are the roles of fat-soluble vitamins

Act as antioxidants

Name the fat-soluble vitamins

Vitamins A (retinoids)

What is the role of calmodulin in calcium signaling

It mediates many effects of intracellular calcium (Ca2+)

How does AMP regulate glycogen metabolism

It acts as an allosteric regulator activating enzymes involved in glycogen breakdown

What is glycogen

The branched storage form of glucose

What are the main steps of glucose mobilization in the liver

Glycogen → glucose-1-phosphate → glucose-6-phosphate → glucose

What is UDP-glucose

An activated glucose molecule used to extend glycogen chains

What protein acts as a primer for glycogen synthesis

Glycogenin

How are glycogen synthesis and breakdown regulated

They are reciprocally regulated by allosteric interactions and covalent modification of enzymes

Which hormones control glycogen metabolism

Insulin

What is the main difference between glucokinase and hexokinase

Glucokinase (in liver and beta cells) is not inhibited by G6P

What is the role of F-2

6-BP in glycolysis

How does the insulin:glucagon ratio affect glycolysis

High insulin:glucagon favors glycolysis and glycogenesis

What enzyme converts glucose to glucose-6-phosphate

Hexokinase or glucokinase

What enzyme catalyzes the conversion of fructose-6-phosphate to fructose-1

6-bisphosphate

What is the regulatory mechanism for pyruvate kinase in the liver

It is inhibited by phosphorylation during fasting and activated by dephosphorylation during the well-fed state

What is the role of lactate dehydrogenase

It reduces pyruvate to lactate to regenerate NAD+ under anaerobic conditions

What is the Cori cycle

The cycle where lactate produced in muscle and erythrocytes is transported to the liver and converted back to glucose

What is signal transduction

The process where an external hormone or neurotransmitter binds a receptor and amplifies a signal inside the cell without entering it

What are the three main types of GPCRs

Gs (stimulatory) Gi (inhibitory) and Gq (phospholipase C coupled)

What type of receptor is the insulin receptor

A tyrosine kinase receptor with extracellular insulin-binding and intracellular catalytic domains

Which tissues are most sensitive to insulin

Adipose skeletal muscle and cardiac muscle

What happens to the insulin receptor upon insulin binding

Conformational change activates its intracellular tyrosine kinase domain

What is phosphorylated by the activated insulin receptor

Insulin Response Substrates (IRS proteins) inside the cell

What is the net effect of insulin receptor activation

Dephosphorylation of regulatory proteins and enzymes promoting the well-fed state

What is the general structure of GPCRs

Seven transmembrane passes with extracellular ligand binding and intracellular G-protein binding domains

What happens when glucagon binds its GPCR

The alpha subunit exchanges GDP for GTP and activates adenylyl cyclase

What is the secondary messenger produced by adenylyl cyclase activation

cyclic AMP (cAMP)

What is the effect of cAMP inside the cell

It activates protein kinase A which phosphorylates regulatory proteins and enzymes

How does glucagon signaling via GPCR affect enzyme phosphorylation

It increases phosphorylation of target proteins

How does insulin signaling differ from glucagon signaling in terms of phosphorylation

Insulin signaling causes net dephosphorylation while glucagon causes phosphorylation

What role do kinases and phosphatases play in insulin and glucagon signaling

Kinases add phosphate groups and phosphatases remove them to regulate enzyme activity

What is the significance of signal amplification in hormone signaling

One hormone binding event can trigger many intracellular changes quickly and efficiently

Signal transduction means the hormone or neurotransmitter does not cross the plasma membrane it binds to a cell surface receptor initiating an intracellular reaction cascade

Hormone or neurotransmitter binds selectively and with high specificity due to the ligand-binding domain’s 3D structure that forms favorable intermolecular forces with the ligand

Different cells express different receptor types and numbers resulting in varying sensitivities and metabolic responses under well-fed and fasting states

Guanosine Protein Coupled Receptors (GPCRs) have a 7-pass transmembrane structure with subunits a

b

The three types of GPCRs differ by their a-subunit: Gs stimulates adenylate cyclase increasing cAMP

Gi inhibits adenylate cyclase decreasing cAMP

Hormone or neurotransmitter binding to receptors triggers physiological responses including covalent modification of regulatory proteins

opening ion channels

Second messengers such as cAMP

Ca2+

Three enzymes produce second messengers: adenylate cyclase (cAMP)

phospholipase C (IP3 and DAG)

The adenylate cyclase system is used by glucagon

epinephrine

cAMP activates protein kinase A which phosphorylates regulatory proteins and enzymes in the target cell

Signal termination occurs when phosphodiesterase converts cAMP to AMP

Phospholipase C system is activated by epinephrine binding α-adrenergic receptors leading to production of IP3 and DAG from PIP2

IP3 increases intracellular Ca2+ by opening ion channels in the endoplasmic reticulum

Increased Ca2+ binds calmodulin activating Ca2+/calmodulin-dependent protein kinases which phosphorylate regulatory proteins and enzymes

Physiological effects include smooth muscle myosin activation

glycogenolysis

Tyrosine kinase system is used by insulin and insulin growth factors whose receptor has an extracellular ligand-binding domain and an intracellular catalytic tyrosine kinase domain

Insulin binding induces conformational changes activating tyrosine kinase which autophosphorylates the receptor and phosphorylates insulin response substrates

Phosphorylated IRS proteins initiate cascades leading to covalent modification of intracellular regulatory proteins and enzymes

Responses include nutrient distribution and recruitment of GLUT transporters to the plasma membrane especially in skeletal muscle and adipose tissue