Phospholipids and cholesterol

human lipids are divided into two categories

nonpolar lipids and polar lipids

nonpolar lipids

triacylglycerols and cholesterol esters (these have hydroxyls but not enough to make them polar)

polar lipids

amphipathic and phospholipids

what do human lipids do

involved in membrane, cell to cell recognition, contact growth control, phagocytosis, aid in conducting nerve impulses, hormones like prostaglandins

phospholipids

two major classes include triacylglycerols and glycerophospholipids, and they have stereospecificity

glycerol

the fundamental structural elements of glycerophospholipids, neutral triacylglycerols, and charged ionic phospholipids have sig different properties and functions

membrane phospholipids

the highest concentration of phospholipids and have structural and functional roles

lung function

requires dipalmitoyl lecithin because it breaks up the surface tension of water, which makes sure water does not adhere to itself to reduce the surface tension of the lungs and cause collapse, it helps maintain flexibility and prevent atelectasis

atelectasis

collapsed alveolus lacking surfactant

respiratory distress syndrome

-accounts 15-20 percent of neonatal deaths in west countries, only on premature babies and incidence varies with degree of prematurity

-due to deficiency of pulmonary surfactant and lecithin/sphingomyelin ratio in amniotic fluid.

-The ratio is supposed to be 2

therapy for respiratory distress syndrome

replacement of surfactant from human or animal lungs, and disease revolves over time as the type 2 cells mature

can respiratory distress syndrome happen in adults

yes if there was death of type 2 cells from either chemo or immunosuppressents

entropy in cholesterol

is minimal, so it is good to use in drugs because it has a conjugated ring system, so it works

key concept of cholesterol

cholesterol is a critical material and humans have an absolute requirement for it and it is important in cell membranes, bile salts and hormones

cholesterol is

ubiquitous

bile phospholipids

solubilize cholesterol and are made in liver

disturbance in phospholipid membrane result in

gall stones, which are just cholesterol-rich depositions in teh gallbladder

what does cholesterol do in the gall bladder

protects it from bile salts because we can't absorb this material without it, cholesterol helps regulate this because it can dissolve cell membrane

where do we get cholesterol

in diet, de novo synthesis and abundant in myelinated structure cannot be oxidized to CO2 and water in humans

how do we get rid of cholesterol

excretion is through the liver and gallbladder as bile acids into the intestines

what do we use cholesterol for

the immediate precursor to bile acids, which is necessary for the absorption of dietary triacylglycerols and fact-sold bell vitamins

cholesterol is a precursor to what

steroid hormones, including progesterone, corticosteroids, aldosterone, estrogen, and testosterone, formation of vitamin D2

three stages of synthesis of cholesterol

1. cytosol

2. lumen of the ER

3. lumen of the ER

cytosol stage

synthesis of isopentenyl pyrophosphate

lumen of the smooth ER

condensation of 6 molecules of isopentenyl pyrophosphate to form squalene

lumen of er third stage

cyclization of squalene and conversion to cholesterol

rate limiting step of cholesterol synthesis

HMG CoA to Mevalonate using HMG CoA reductase

building block of cholesterol synthesis

3 isopentenyl pyrophosphate

HMG CoA reductase key concept

the enzyme that catalyzes the rate-limiting step of cholesterol biosynthesis

regulation on HMG CoA reductase

control with cholesterol

genetic regulation for reductase mRNA

sterol regulatory element binding protein which helps shut down making mRNA

rate of translation

inhibited by mevalonate-derived intermediates and dietary cholesterol

rate of degradation of HMG CoAR

membrane domain alters conformation in response to sterols, which enables proteolysis, meaning the degradation of enzymes

phosphorylation

switched off by AMp-activated protein kinase

vitamin d3

derived from a photo reaction involving cholesterol, makes provitamin D, converted to vitamin D is slow being 36 hr, no enzyme required

how much sunlight exposure should you have a day to keep vitamin D levels stable

10 mins per day on hands and face

prostaglandins

promote contraction of intestinal and uterine muscles, lower blood pressure, highly important medically, produced by almost all cells except RBC, not stored, control is not understood

importance of prostaglandins

mediators of inflammation for tissue damage, cause vasodilation (swelling and edema due to capillary leakage), and is treated with corticosteroids to inhibit prostaglandin production, cause cell migration, enhance pain caused by histamine and bradykinin, generated in response to fever, synthetic forms are useful for patients with a peptic ulcer which inhibits gastric acid secretion