CMB 704 Block 4

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in collagen synthesis, a chain residues are glycosylated and hydroxylated in

golgi/ER

In collagen synthesis, procollagen triple-helix formation and secretion take place in

secretory vesicle

Which substance, under physiologic conditions, is essential to the transformation of G-actin to F-actin

ATP

Once F-actin is formed from G-actin what is it called

microfilament

In skeletal muscle, excitation-contraction coupling is mediated by what

release of calcium from sarcoplasmic reticulum

Calcium regulation of skeletal muscle contraction

1. action potential depolarizes membrane potential
2. SR releases Ca2+ which binds to troponin C
3. Troponin C modulates Troponin I conformation
4. myosin binding site on actin is exposed
5. Ca2+ is pumped back out to ER in msec

what modulates the troponin I conformation

troponin C

Sarcoplasmic reticulum release of Ca2+ binds what

Troponin C

During contraction, what does not change in width or length?

A band (thick)

Epinephrine causes an elevation in cAMP levels in muscle cells which in turn activate

protein kinase

What type of hormones bind to specific receptors on the cell surface, and a signal is transmitted to the interior of the cell as a result

hydrophilic hormones

in hydrophilic hormones, the interaction between hormones and their receptors is

reversible

As the hormone levels decline, the hormone action ________________ as the hormones dissociate from their receptors

declines

thyroid and steroid hormones are considered

lipophilic

what subunit of Gs protein exchanges GDP for GTP, dissociates from the G beta gamma subunits, and activates adenylate cyclase

G alpha

what G subunit is a GTPase and eventually hydrolyzes the GTP that is bound to it

G alpha

the hydrolysis of what inactivates the G alpha protein, which then reassociates with G beta-gamma where it remains until it is reactivated by a hormone-receptor complex

GTP

What G protein stimulates the enzyme adenylate cyclase

Gs

what G protein inhibits the enzyme adenylate cyclase

Gi

what G protein stimulates the enzyme phospholipase C

Gq

Levels of cAMP quickly declines because it is hydrolyzed by

cyclic nucleotide phosphodiesterase (PDEase)

Phospholipase C-beta cleaves IPI2 to form

IP3 and DAG (no cAMP is formed)

cAMP binds to the regulatory (R) subunits of cAMP-dependent protein kinase and causes them to be released from the

catalytic (C) subunits

the active ____ subunits phosphorylate specific proteins in the cell

C

Phospholipase C is a type of enzyme that hydrolyzes PIP2 to

IP3 and DAG

IP3 and DAG are ______________ _________________ , which means that they carry information from the hormone-receptor complex to molecules within the cell

secondary messangers

IP3 diffuses into what

cytosol

IP3 in the cytosol, causes the release of calcium ions from intracellular stores, and DAG activates

protein kinase C

IP3 is rapidly inactivated by

dephosphorylation

DAG is rapidly deactivated by

hydrolysis

what type of hormones have a longer duration of action

lipophilic hormones - interact with intracellular receptors, because they affect gene expression

insulin, glucagon, epinephrine, and epidermal growth factor (EGF) are considered

hydrophilic hormones

Insulin binds to a transmembrane receptor at the outer surface of the plasma membrane, which activates

tyrosine kinase receptor that is the cytosolic domain of the receptor

the binding of insulin to the alpha subunits causes a conformational change in

beta subunit

Beta subunit phosphorylate _____________ ______________ located in the cytoplasmic domain of the receptor

tyrosine residues

how is tyrosine kinase activated

by the binding of insulin

some hydrophilic hormones, such as glucagon and epinephrine, lead to the activation of _______________ ________________ through the Gs protein

adenylate cyclase

what can insulin not readily diffuse across the cell membrane

because it is hydrophilic

Plasminogen activator binds to fibrin clots and activates the conversion of plasminogen to

plasmin

what specifically degrades clots

plasminogen activator (plasminogen to plasmin)

thrombin is a procoagulant and can only

Increase clot formation

Heparin and hirudin are anticoagulants which

inhibits formation of clots

factors involved in the intrinsic pathway

XI, IX, and VIII

factors involved in the extrinsic pathway

III and VII

factors involved in the common pathway

I, II, V, and X

pertussis toxin is infectious disease which causes whooping cough by

irreversibly activating adenylate cyclase

pertussis toxin is an enzyme that modifies the

alpha subunit of Gi

during pertussis, the Gi modification prevents Gi from exchanging

GDP for DTP

normal serum calcium values

8.5-10.5 mg/dL

where does this reaction take place:
7-dehydrocholesterol --> cholecalciferol

skin

where does this reaction take place:
cholecalciferol --> 25-hydroxy-vitamin D3

liver

where does this reaction take place:
25-hydroxy-vitamin D3 --> 1,25-dihydroxy vitamin D3

kidney

what is a direct result of the parathyroid hormone

inhibition of osteoblasts apoptosis

what is the mechanism of action for the effect of estrogen on bone mineralization

inhibits osteoclast action

bone mineralization process

1. collagen fiber secretion
2. amorphous calcium phosphate deposition
3. hydroxyapatite crystal formation
4. growth of crystal lattice

ligand-gated ion channels in nerve cells open in response to

the binding of a neurotransmitter

proteins present in the saliva

IgA
EGF
lipase
mucin

what constitutes the largest family of cell-surface receptors

GPCRs

GPCRs activating mutations causes what even in the absence of ligand

GPCR signal transduction

ligand binding to the _________ causes a conformational change that allows them to directly interact with and activate G-proteins

GPCRs

Intracellular receptors regulate gene expression functioning as

transcription factors

what activate PKC leading to increase phosphorylation of PKCs target proteins

DAG and Calcium

what is the precursor of all steroid hormones

cholesterol

When a chemical messanger (or ligand) reaches a target cell, it binds to a receptor. A hydrophobic ligand binds to a _________________, whereas a hydrophilic ligand binds to a _______________

intracellular receptor; transmembrane receptor

calmodulin activates target proteins in the presence of

calcium

what muscle component can bind or sequester calcium ions

troponin C

Which type of cells is characterized by having limited cell to extracellular matrix contacts and abundant cell to cell contacts

epithelium

what type of cells is characterized by having abundant cell to extracellular matrix contacts and limited cell to cell contacts

connective tissue

the common pathway of coagulation begins with

activating of a clotting factor that converts prothrombin to thrombin

the final reaction of the common pathway is the conversion of what

fibrinogen to fibrin

what separates the epithelial cells from the underlying connective tissue

basal lamina

the enzyme responsible for forming the major storage form of energy needed for muscle contraction

creatine kinase

upon contraction, ATP concentration is maintained until phosphocreatine is depleted, then, more ATP is made by

adenylate kinase

creatine --------> phosphocreatine uses what enzyme

creatine kinase

what is the primary component of a stable blood clot

fibrin

what serine protease catalyzes the conversion of fibrinogen to fibrin

thrombin

proteins found in saliva

proline-rich proteins
mucin
epidermal growth factor
IgA

heparin, hirudin, coumarin, and warfarin are all examples of what

anticoagulant

what protein breaks F-actin filaments and caps the + end

gelsolin

saliva provides ____________ and ______________ for remineralization

calcium and phosphate

what inhibits the formation of primary and secondary calcium phosphate salts

statherin

what is the primary class of antibody found in secretions, such as tears and saliva

IgA

what saliva component has high elasticity, adhesiveness, low solubility and resists dehydration

mucins

Factor XII, plasma prekallikrein, coagulation Factor XI, and kininogen

intrinsic pathway

peptide hormones are _____________ in lipids

insoluble

what form rivet-like links between cytoskeleton and extracellular matrix components

hemidesmosomes

the metabolic changes in type 2 diabetes

1. hyperglycemia - increase plasma glucose
2. hypertriacylglycerolemia

the metabolic changes in type 1 diabetes

1. Hyperglycemia - increase plasma glucose
2. ketonemia - increase plasma ketone bodies
3. Hypertriacylglycerolemia - increase plasma TAG

normal range of plasma glucose

100 mg/dL

normal range of HbA1c

around 6%

what is the most abundant intracellular anion

phosphate

what is the most abundant mineral in the body

Calcium

parathyroid hormone and 1, 25 hydroxyl vitamin D3 - calcitriol both do what

increase serum calcium

parathyroid hormone main effects in bone

1. increases osteoblast proliferation and differentiation
2. decreases osteoblast apoptosis
3. enhances the Wnt-B catenin pathway, central to osteogenesis and bone formation, inhibiting sclerostin

what is the primary component of bone, dentin, and enamel

inorganic biological apatite (hydroxyapatite)

bone and dentin are 30% organic which is mostly

type 1 collagen

what pump in the osteoclast membrane lowers the pH in the space between the osteoclast and the bone

ATP-driven proton pump

what mineral is the most resistant to the enamel dissolving acid produced by bacteria in the mouth

fluoroapatite

where is insulin synthesized

B cells

where is glucagon synthesized

alpha cells

Where is the body are insulin and glucagon produced

pancreas

where does glycogen synthesis take place

skeletal muscle

where does TAG synthesis take place

adipose

where does catecholamine synthesis take place

adrenal glands and sympathetic nervous system

stages of insulin synthesis

1. transcribed, mRNA moves to cytosol
2. on rough E.R. translated to preproinsulin
3. in E.R. lumen, cleaved to proinsulin
4. In golgi, cleaved to insulin and C-peptide

glucose
amino acids
G.I hormones
all promote

insulin secretion

catecholamines
scarcity of dietary fuels
all decrease

insulin secretion

decreased blood glucose - fasting / increased glucagon prevents hypoglycemia
amino acids
catecholamines
all increase

glucagon secretion

high blood glucose
insulin
all decrease

glucagon secretion

metabolic effects of insulin

- increased glycogen synthesis
- decreased glycogenolysis and gluconeogenesis
- reduces fatty acid release and promotes fatty acid storage

metabolic effects of glucagon

- increases gluconeogenesis
- increased glycogenolysis

what is the by product of ethanol metabolism causes a decrease in liver gluconeogenesis

NADH

what is the most common type of hypoglycemia

postprandial (period of time after a meal)

what state does insulin increase and glucagon secretion decreases

Absorptive or well-fed state

the anabolic period where there is an increase of TAG, glycogen, and protein occurs in what state

absorptive (feed state)

4 regulatory mechanisms in the feed-fast cycle

1. availability
2. allosteric regulation
3. covalent enzyme modification
4. enzyme synthesis

what promotes dephosphorylation, and activation of glycogen synthase (an enzyme for glycogen synthesis)

Insulin

what promotes phosphorylation, and activation of glycogen phosphorylation (a enzyme degradation; glycogenolysis)

glucagon

what regulatory mechanism in the feed-fast cycle is most common that is involved in phosphorylation/dephosphorylation

covalent enzyme modification

increased glucose phosphorylation to glucose-6-phosphate by glucokinase leads to

1. increased glycogenesis
2. increased pentose phosphate pathway
3. increased glycolysis --> leads to increased acetyl CoA

what is the source of fatty acids for TAG synthesis in the liver during the absorptive state

Acetyl CoA
Chylomicron

where is TAG synthesis packaged and sent to adipose and muscle tissue

VLDL

Increased glucose uptake by __________ transporters - glucose phosphorylated by _______________

GLUT-4 ; hexokinase

what is the 1st source of glucose - about 2-3 hours after a meal

glycogenolysis
Next - gluconeogenesis (2-4) hours after a meal)

in the fasting state, what are the byproducts of fatty acid oxidation

Acetyl CoA and NADH

major fuel source in resting muscle

fatty acids

Type 1 diabetes results from an autoimmune attack on pancreatic ___ cells

Beta

which diabetes has a environmental stimulus

type !

type 1 diabetes metabolic changes

1. hyperglycemia - increase plasma glucose
2. Ketonemia - increase plasma ketone bodies
3. hypertriacyglycerolemia - increase plasma TAG

what is the most common complication of insulin therapy

insulin-induced hypoglycemia

what results from the combination of insulin resistance and dysfunctional Beta cells

Type 11 diabetes

Insulin resistance increases with

weight gain

what is the most common cause of insulin resistance

obesity

obesity causes adipose to secrete

- proinflammatory cytokines
- increased amounts of leptin
- decreased amounts of adiponectin

type 2 diabetes metabolic changes

1. hyperglycemia - increase plasma glucose
2. hypertriacylglycerolemia

what type of adipose is the most metabolically active - high rates of lipolysis, free fatty acid mobilization

visceral adipocytes

what receives the venous drainage of visceral and abdominal adipocytes

liver

_________ gene mutations cause hyperphagia and obesity

leptin