Unit 3 ALL Learning Objectives

glycogenolysis

breakdown of glycogen

gluconeogenesis

synth. glucose from non-carb. sources

glycogenolysis

breakdown of stored glycogen into glucose-1-phosphate + glucose

lipolysis

lipid mobilization

metabolism definition

structures and processes coordinated in space + time

chemical reactions that sustain life

metabolism pathway

brain senses hunger/satiety

organism eats/digests

cells process food into usable energy (cellular respiration)

cellular and physio. functions (eg. DNA repair, homeostasis)

metabolism overview

gut brain connections

similar hormones produces in gut + brain

hormone produced in gut (stim. by ingestion) impact hormone prod. in brain

brain to gut axis (influence on)

motility

secretion

nutrient delivery

microbial balance

gut to brain axis (influence on)

neurotransmitters

stress/anxiety

mood

behavior

regulation of feeding

brain takes in info. from surroundings (sensory) + periphery (body physios.)

integrates signals

makes decisions on what + when to eat

center’s influence on appetite

orexigenic center stimulates

anorexigenic center inhibits

feeding regulator hormones

neuroPeptide Y (NPY)

galanin

orexin

ghrelin

leptin

insulin

cholecystokinin (CCK)

cocaine-amphetamine-regulated transcript (CART)

cortisol

orexigenic hormones produced in brain

neuropeptide Y (NPY)

ghrelin

galanin

orexin

hormones that reg. feeding produced outside of brain

ghrelin (O)

leptin (A)

insulin (A)

cholecystokinin (CCK) (A)

cortisol (A)

neuropeptide y (NPY) structure

36 aa

neuropeptide y (NPY) produced in

hypothalamus + nerve fibers in S. Int

neuropeptide y (NPY) O or A

orexigenic

galanin structure

29 aa

galanin produced in

CNS (hypo + pit.) + GI Tract

galanin O or A

orexigenic

orexin structure

neuropeptide (isoforms)

28, 33, 34 aa

pre-pro hormone

orexin produced in

hypothalamus

orexin O or A

orexigenic

ghrelin structure

28 aa

N-end fatty acid chain

peptide

ghrelin produced in

stomach/anterior gut

hypothalamus

(targets brain)

ghrelin O or A

orexigenic

leptin structure

167 aa peptide

leptin produced by

white adipose tissue (fat)

(targets the hypothalamus)

leptin O or A

anorexigenic

leptin function

signal of whole body energy levels (fat)

insulin structure

A (21 aa) + B (30 aa) peptide chains linked by disulfide bonds

insulin produced by

pancreatic beta cells

insulin O or A

anorexigenic (at high concentrations)

insulin function

signals the body has incoming fuel + doesn’t need to eat more

cholecystokinin (CCK) structure

pre-pro peptide

several diff. length isoforms (58, 33, 22, 8)

mature (bioactive) form has sulfate group (-SO3)

cholecystokinin (CCK) produced by

duodenum + brain

cholecystokinin (CCK) O or A

anorexigenic

(in response to food in GI tract)

cortisol structure

steroid-based

cortisol secreted by

adrenal cortex in response from ACTH from pit. + CRH from hypothal.

cortisol O or A

anorexigenic

cortisol function

metabolize stored energy

released in response to stress

cocaine-amphetamine-regulated transcript (CART) structure

neuropeptide

several lengths produced (41 aa)

cocaine-amphetamine-regulated transcript (CART) produced in

brain + intestines

cocaine-amphetamine-regulated transcript (CART) function

works synergistically with CCK

gastrointestinal tract cells description

endocrine cells dispersed thru out epithelial lining (NOT CLUMPED)

stim. of cells from luminal side

hormones released at basal side into circulation

hormone families (structural)

gastrins

secretins

PYY, NPY, PP

ghrelin

leptin

2 features that make gastrins structurally similar (gastrin + CCK)

sulfation (SO3H) - increases receptor binding

bioactive N-terminus

secretins types (family)

secretin

glucagon

vasoactive inhibitory peptide (VIP)

gastric inhibitory peptide (GIP)

secretins structure (family)

similar primary sequences (human/pig/rat)

individual hormones well conserved

PYY, NPY, PP acronyms (family)

peptide YY

neuropeptide Y

pancreatic polypeptide

PYY, NPY, PP structurally similar? (family)

cleavage sites

ghrelin produced in? (family)

stomach + brain

ghrelin structure (family)

precursor protein + modified into 28 aa mature hormone

fatty acid chain near N-terminus

leptin structure (family)

class I alpha-helical cytokines

precursor → mature: 150 aa

A-D helices

critical disulfide bond (for fx)

leptin produced in? (family)

adipose + other tiss.

pathway of digestion

mouth

esophagus

stomach

pylorus

SI

LI

other organs involved in digestion

liver

gallbladder

pancreas

mouth role in digestion

mechanical digestion (chewing + swallowing)

chemical digestion of carbohydrates

stomach role in digestion

mechanical digestion: peristaltic mixing + propulsion

chemical digestion: proteins

absorption: lipid-soluble substances

small intestine role in digestion

mechanical digestion: mixing + propulsion, primarily by segmentation

chemical digestion: carbs., lipids, + nucleic acids

absorption: peptides, AA, glucose, fructose, lipids, water, minerals + vits.

large intestine role in digestion

mechanical digestion: segmental mixing, mass movement for propulsion

NO chemical digestion except by bacteria

absorption: ions, water, minerals, vits., small organic molecules from bacteria

hormone function + digestion in mouth

sensory input (smell) stims. increased CNX outflow to stim,

• saliva production

• gastrin release in stomach

hormone function + digestion in stomach

presence of aa/proteins in gut stims.. gastrin in stomach → inc.

• churning

• HCl secretion (activates proteases + denature proteins)

• pepsinogen release (+HCl → pepsin) protein-digestive enzymes

• grow stomach mucosa

hormone function + digestion in duodenum

increased H ions (acidity) stims. secretin release in duodenum

• inc. bicarbonato (HCO3-) secretion from pancreas

  • neutralizes acidity

• increase CCK release from duodenum

  • inc. bile secretion (relax bile sphincter + contr. smooth muscle in gallbladder)

  • help secretin stim. of HCO3- from pancreas

  • satiety in CNS

  • stims. zymogen release from pancreas acinar cells (zymogens→hydrolases)

gastric inhibitory protein (GIP) structure

43 aa

gastric inhibitory protein (GIP) stimulated by

fats in duodenum

gastric inhibitory protein (GIP) functions

stims. insulin secretion

activates lipoprotein lipase (LPL)

inhibits gastric acid

motilin structure

22 aa

GI peristalsis (from stomach to duodenum by pyloric valve)

motilin synthesized by

endocrine cells throughout duodenum

vasoactive inhibitory peptide (VIP) structure

28 aa

vasoactive inhibitory peptide (VIP) function

vasodilator + lowers BP (relaxes smooth muscle + blocks vasoconstrictors)

intermediary metabolism definition

events that occur

• after food has been digested + absorbed into BS

• before cells use in cellular respiration

carbohydrate regulation

vertebrates regulate blood glucose levels

• 120 mg/dL or 5.5 mM (across vertebrates)

• 70-120 mg/dL in fasted humans

hyperglycemia definition

digestion breaks down + absorbs carbs into the blood

hormones regulate/stabilize

hypoglycemia definition

fasting decreases blood glucose

hormones regulate/stabilize

hyperglycemic compensation

1. eating, digestion, + absorption INC blood glucose

2. high blood glucose triggers insulin to release into blood

3. insulin signals cells to take up glucose

4. ends in DECR glucose levels

insulin → GLUT4 mechanism

1. high blood sugar is sensed by pancreatic cells that then stim. to synthesize/secrete insulin into blood

2. insulin detected by body cells + triggers cells to express glucose transporters on plasma membrane

3. glucose transporters (GLUT4) facilitates diffusion of glucose into cell from blood

hypoglycemic compensation

cells uptake glucose to fuel cellular → physio. functions

low blood glucose

triggers liver to mobile glucose by breaking down glycogen (glycogenolysis)

• de novo synthesis of glucose from non-CHO source (gluconeogenesis)

blood glucose increases

triggers hyperglycemic compensation

pancreas tissues

acinar cells: smaller + dark pink

islet of langerhans: larger + light pink

islet of langerhans

alpha (A) cells

beta (B) cells

delta (D) cells

PP (F) cells → pancreatic polypeptide

insulin processed by

pre-pro insulin of DBCA chain

insulin structure

5 min half life

A chain: 21 aa residues + 1 intra disulfide bond

B chain: 30 aa

insulin receptor structure

2 alpha + 2 beta subunits

insulin receptor alpha structure

extracellular

ligand binding

disulfide bonds

• btw alphas

• btw alpha + beta

insulin receptor beta structure

transmembrane

transmits signal

RTK (receptor tyrosine kinase)

disulfide bonds

• btw alpha + beta

insulin receptor mechanism of action

insulin receptor substrate (IRS) binds alpha

transmits conformational change to beta

beta auto-phospholates = activate tyrosine kinase activity

phosphor. (activates) downstream: IRS → PI3K/Akt → GLUT4 expression on plasma membrane

OR

Grb2 → MAPK (ras, raf, mek, erk, elk, transcription)

insulin functions

glucose transport systems

glycogen synthesis

cell growth (proliferation)

glucagon structure

29 aa

species variation

from large precursor (processed diff. in diff. tissues)

• GLU: glucagon

• GLP: glucagon-like peptide

insulin affect on blood sugar

decreases

(allows glucose to move from blood into cells for energy)

glucagon affect on blood sugar

increases

insulin affect on the liver

promotes glucose storage as glycogen (glycogenesis)

inhibits glucose production (gluconeogenesis/glycogenolysis)

stims. fat synthesis (lipogenesis)

glucagon affect on the liver

stims. glycogenolysis (breaks down stored glycogen into glucose)

prom. fatty acid oxidation

reduces glucose production

insulin affect on adipose tiss.

prom. energy storage

reducing fat breakdown (lipolysis)

stims. glucose + fatty acid uptake from bloodstream

stims. lipogenesis

glucagon affect on adipose tiss.

increases lipolysis

triggers fatty acid release

reduces adipogenesis (fat cell prod.)

insulin affect on muscle

glucose uptake

glycogen storage

incr. aa

stims. protein synthesis

glucagon affect on muscle

prom. breakdown of skeletal muscle

release aa for gluconeogenesis

reduces protein synthesis

somatostatin produced by

delta (D) cells of pancreas

somatostatin function

inhibits alpha cells from secreting glucagon

inhibits beta cells from secreting insulin

somatostatin stimulated by

high plasma conc. of glucose, aa, + fatty acids

somatostatin function

modulates blood glucose