Pulm/Renal - Biochemistry - Phospholipids, Sphingolipids, Eicosanoids; the Urea Cycle: Hyperammonemias; Nucleotide Metabolism Flashcards
Name three subtypes of phospholipid.
Phosphoglycerides
Plasmalogens
Sphingolipids
Describe the differences in chemical structure between the following phospholipids:
Phosphoglycerides
Plasmalogens
Sphingolipids
Phosphoglycerides - polar head + 2 esterified fatty acids
Plasmalogens - polar head + 1 esterified fatty acid + 1 etherified fatty acid
Sphingolipids - polar head + 1 ceramide (amide-bonded fatty acid) + 1 sphingosine (enol attachment)
What are the two main types of sphingolipid?
- Sphingomyelin
- Glycolipids (e.g. glucocerebroside, gangliosides, etc.)
Sphingomyelin is basically a phospholipid (specifically, a sphingolipid) with what polar head?
Phosphocholine
What are the basic steps of phosphoglyceride synthesis?
DHAP or glycerol –>
glyceral 3-phosphate –>
activated fatty acic groups added to C1 and C2 –>
head group attached to 3-phosphate
What are the three tissues that are major producers of phosphoglycerides?
Liver
Intestinal epithelium
Lungs (for surfactant)
What are the two major components of pulmonary surfactant?
Surfactant is __% lipid and __% protein.
Dipalmitoylphosphatidylcholine (DPPC),
phosphatidylglycerol;
90, 10
You need to determine fetal surfactant production. Where do you get a sample?
A lecithin:sphingomyelin reading of 1.2 indicates what?
(Note: lecithin is an old term for phosphatidylcholine)
The amniotic fluid;
immature production (<2.0)
What substance should be given to mothers going into preterm labor to reduce their child’s risk of respiratory distress syndrome?
Glucocorticoids
What effect does surfactant have on the alveolus?
Decreased surface tension / elastance;
increased compliance
What is a normal lecithin:sphingomyelin reading for mature lungs?
(Note: lecithin is an old term for phosphatidylcholine)
2:0 - 2:5
Lecithin:sphingomyelin levels are useful in measuring lung maturity.
Lecithin is another name for what substance?
Phosphatidylcholine
Besides their structural role in membranes, what role do plasmalogens (a type of phospholipid) have in cellular protection?
They act as ‘scavengers’ for free radicals, sparing nearby fatty acids and other structures
The nomenclature of plasmalogens is similar to phosphoglycerides.
Describe any differences, using phosphatidylcholine as an example phosphoglyceride.
Phosphoglyceride: Phosphatidylcholine
Plasmalogen: Phosphatidalcholine
Where does plasmalogen (a type of phospholipid) synthesis occur?
What disorder results when peroxisome biogenesis is inhibited?
Peroxisomes;
Zellweger syndrome (death usually occurs within 6 mo. - 1 year following birth)
What enzyme cleaves the C-1 esterified fatty acid from a phosphoglyceride?
What enzyme cleaves the C-2 esterified fatty acid from a phosphoglyceride?
What enzyme cleaves the C-3 phosphate group from a phosphoglyceride?
Phospholipase A1;
phospholipase A2;
phospholipase C
What enzyme cleaves the C-1 esterified fatty acid from a phosphoglyceride?
Phospholipase A1
What enzyme cleaves the C-2 esterified fatty acid from a phosphoglyceride?
Phospholipase A2
What enzyme cleaves the C-3 phosphate group from a phosphoglyceride?
Phospholipase C
Name the function of each of the following:
Phospholipase A1
Phospholipase A2
Phospholipase C
Cleave the phosphoglyceride C-1 fatty acid from the glycerol back bone
Cleave the phosphoglyceride C-2 fatty acid from the glycerol back bone
Cleave the phosphoglyceride C-3 phosphate group from the glycerol backbone
All sphingolipid synthesis start with a simple ___________.
To create sphingomyelin, add ___________.
To create glucosylcerebroside , add ___________.
To create galactosylcerebroside , add ___________.
Ceramide;
phosphocholine,
glucose,
galactose
Sulfatides are a type of sphingolipid made by the ____________ of galactosylcerebrosides in the CNS oligodendrocytes.
If multiple sugars are added to a ceramide, a ______________ results. Adding ________ acid to this results in a ganglioside.
Sulfation;
globoside,
sialic (N-acetylneuraminic)
Type A Niemann-Pick disease results from dysfunction in the metabolism of what substance?
Type B Niemann-Pick disease results from dysfunction in the metabolism of what substance?
Type C1 Niemann-Pick disease results from dysfunction in the metabolism of what substance?
Type C2 Niemann-Pick disease results from dysfunction in the metabolism of what substance?
Sphingomyelin;
sphingomyelin;
cholesterol;
cholesterol
How does type A Niemann-Pick disease manifest?
How does type B Niemann-Pick disease manifest?
More severe form: sphingomyelin accumulation in liver, CNS, and spleen
–> neurodegeneration/intellectual disability and early death;
less severe form: no significant neurological involvement
–> patients typically survive into adulthood
What two enzymes are responsible for sphingomyelin degradation?
Which is deficient in type A Niemann-Pick disease?
Which is partially inactivated in type B Niemann-Pick disease?
Sphingomyelinase, ceramidase;
sphingomyelinase;
sphingomyelinase
What two enzymes are responsible for sphingomyelin degradation?
A deficiency of which enzyme is responsible for Farber disease? What accumulates in this disorder?
Sphingomyelinase, ceramidase;
ceramidase, ceramides
Metachromatic leukodystrophy results from a deficiency of what enzyme?
Resulting in a buildup of what substance?
Arylsulfatase;
sulfatides
Virtually each sphingolipidosis is due to a defect in metabolic pathways breaking down substrate to what eventual product?
Ceramide
What are the three main eicosanoids?
What are eicosanoids?
Prostaglandins, thromboxanes, leukotrienes;
potent cellular regulators: short-lived, local/paracrine signalling molecules
What are some of the functions of eicosanoids?
Pain, swelling, fever (prostaglandins)
Blood coagulation (thromboxanes)
Inflammatory response (leukotrienes)
Eicosanoids are derived from what precursor?
How does this precursor become available?
Arachidonic acid (an ω-6 fatty acid);
(1) phospholipase A2 cleaves it from the C-2 of membrane phospholipids,
(2) it is synthesized from linoleate
How do glucocorticoids decrease the availability of arachidonic acid to a cell?
What immediate effect does this have?
They inhibit phospholipase A2;
decreased eicosanoid (prostaglandins, leukotrienes, thromboxanes) production
What substance inactivates phospholipase A2, thus decreasing the amount of arachidonic acid available to a cell?
Glucocorticoids
After arachidonic acid is cleaved from C-__ of a membrane phospholipid, what are the enzymes that process it into its eicosanoid (prostaglandins, thromboxanes, leukotrienes) products?
2;
cyclooxygenase-1, cyclooxygenase-2, lipooxygenase
Cyclooxygenases turn arachidonic acid into what initial product? (With what intermediate?)
This product is a precursor to what?
Prostaglandin H2 (PGH2) (with PGG2 as an intermediate);
all other prostaglandins, all thromboxanes
Cyclooxygenases produce what from arachidonic acid?
Lipooxygenases produce what from arachidonic acid?
Prostaglandins, thromboxanes;
leukotrienes
What effect do aspirin and other NSAIDs have on eicosanoid production?
NSAIDs block cyclooxygenase and inhibit its expression,
thus decreasing prostaglandin and thromboxane production
Which NSAID irreversibly acetylates the COX enzymes?
Aspirin
Via what chemical reaction do acetominophen and NSAIDs block the COX enzymes?
Identify any of the following that irreversibly inhibit the COX enzymes:
Acetominophen
Ibuprofen
Ketorolac
Aspirin
Naproxen
Acetylation;
aspirin
What side effects does regular aspirin use have?
Abdominal discomfort, ulcer formation, extended bleeding time
What is the major ingredient in Nuprin?
What is the major ingredient in Motrin?
What is the major ingredient in Advil?
Ibuprofen
Ibuprofen
Ibuprofen
Which is more powerful and longer lasting, ibuprofen or acetominophen?
Ibuprofen
What is a common side effect of ibuprofen use?
What is a potential side effect of frequent acetominophen use?
Stomach irritation;
liver toxicity
True/False.
All of the following are NSAIDs and have anti-inflammatory, anti-pyretic, and analgesic properties.
Acetominophen
Ibuprofen
Ketorolac
Aspirin
Naproxen
False.
Acetominophen is not an NSAID and has no anti-inflammatory properties
What is a dangerous side effect of the medication celecoxib (Celebrex) (a selective COX-2 inhibitor)?
Increased risk of stroke and heart attack
Which COX enzyme is constitutively expressed in nearly all tissues and has normal, physiological functions?
Describe the other COX enzyme.
COX-1;
the COX-2 enzyme is induced by cytokines/growth factors (from activated immune and inflammatory cells), and has activity due to more abnormal, pathologic functions
Which is more responsible for the pain, swelling, redness, and heat associated with inflammatory responses, COX-1 or COX-2?
COX-2
(COX-1 = more physiologic functions;
COX-2 = more pathologic functions)
Which NSAID has antiplatelet activities?
How?
Aspirin;
by irreversibly inhibiting the COX enzymes and decreasing thromboxane A2 synthesis
(the other NSAIDs are reversible)
What is the main thromboxane?
What functions does it have?
Thromboxane A2;
platelet aggregation, vasoconstriction
Which COX enzyme product helps to oppose the platelet aggregation and vasoconstriction induced by thromboxane A2?
Prostaglandin I2 (PGI2) (prostacyclin)
What are the main functions of leukotrienes?
Mediating: (1) the allergic response, (2) vasoconstriction, (3) bronchoconstriction, and (4) chemotaxis
Via what mechanism can aspirin and some NSAIDs cause an overproduction of leukotrienes?
By blocking PG and thromboxane production, the remaining arachidonic acid is shunted to become leukotrienes
In what form are carbohydrates stored in the body?
In what form are lipids stored in the body?
In what form are proteins stored in the body?
Glycogen;
triglycerides;
proteins are not stored in the body (excess protein is rapidly excreted)
What are the three basic steps of amino acid catabolism?
1. A transamination reaction removes the amino group as ammonia (leaving behind a keto acid skeleton)
2. The urea cycle converts the ammonia to urea
3. The ketoacid skeleton is oxidized and converted to useful metabolites (e.g. for anapleurotic reactions)
How does a typical transamination reaction work?
An amino acid and a ketoacid swap an amino group
(converting the ketoacid to an amino acid and the amino acid to a ketoacid)
What cofactor is needed for all transamination reactions?
Pyridoxal phosphate (from pyridoxine, vitamin B6)
What happens to the ammonium (NH4+) that is produced in the first steps of amino acid degradation (when the amino group is removed via transamination reactions)?
It is either:
(1) used in the synthesis of amino acids, biological amines, or nucleotides
or
(2) turned into carbamoyl phosphate to enter the urea cycle
The initital steps of degradation of any amino acid typically involve transamination of the amino acid’s amino group to what molecule?
What is formed?
α-Ketoglutarate;
glutamate
(and the amino acid being degraded is converted to its ketoacid equivalent)
What is glutamate’s corresponding ketoacid (following deamination)?
What is alanine’s corresponding ketoacid (following deamination)?
α-Ketoglutarate;
pyruvate
What is pyruvate’s (a ketoacid) corresponding amino acid (following amination)?
What is α-ketoglutarate’s (a ketoacid) corresponding amino acid (following amination)?
Alanine;
glutamate