Chapter 6: Anabolic Pathways Flashcards
Do anabolic pathways happen in fed state or starvation state?
fed state (anabolic is building)
lipids, proteins, glucose, ketones, glycogen, glucose: in what order are these broken down and in what order are they built back up
broken down: glucose, glycogen, protein, lipids, ketones
built up: same order as above
What hormone allows us to take in glucose?
insulin
What are the second messengers for insulin?
tyrosine kinase, parasympathetic cGMP
What anabolic pathway does glucose activate and which catabolic pathway does glucose inhibit?
glucose activates glycogen synthesis and inhibits gluconeogenesis
5 areas of glycogenesis
liver, skeletal muscle, adrenal cortex, intestinal wall and heart
What are the only 2 organs that can use glycogen for glucose and put it into bloodstream?
liver and adrenal cortex
What drug inhibits gluconeogenesis?
metformin
Which diabetes drug blocks the voltage sensitve potassium channels and promotes insulin release?
sulfonylureas
SE of sulfonylureas
hypoglycemia, sulfa drug reactions, SIADH (Chlorpropamide)
Which DM2 drug blocks postprandial absorption of glucose?
alpha glucosidae inhibitors: acarbose, miglitol
SE of alpha glucosidase inhibitors
abdominal pain, gas, bloating, nausea
If a person is taking metformin, what must you do if he/she needs a contrast CT?
Stop metformin for a few days, then perform CT; if acute, stop metformin, give IV fluids and add NAC to protect kidneys.
Name a few thiazolidinediones for DM2
pioglitazone, rosiglitazone
Name a few incretin mimetics. What do they do?
exenatide, semaglutide: mimic incretins that are secreted by intestinal wall in response to food; potentiates insulin release, inhibits glucagon release, inhibit appetite and food intake (Ozempic)
DPPP4 inhibitors
inhibits degradatoin of GLP-1; more insulin release, inhibit glucagon release
two short acting insulin
regular and lispro
two medium length insulins
NPH and lente
two long acting insulin analogs
ultralente; glargine
What kind of bonds are involved in glycogen chain?
alpha 1,4 bonds
After 8 to 10 bonds on glycogen chain, what kind of bond is needed to branch the chain?
alpha 1,6 bond
Which glycogen storage disease has only straight chains and no branching enzyme?
Anderson’s Disease
What pathway makes ribose 5 phosphate used in DNA and RNA synthesis and NADPH as a byproduct?
pentose pathway (HMP shunt)
What are the uses of NADPH?
DNA synthesis, fatty acid synthesis, RBC repair (glutathione)
What happens in G6PD deficiency?
cannot repair RBC; cannot protect against sulfur reactions
List the X-linked recessive enzyme deficiencies
GOLF PAATCHS
G6PD
OTC
Lesch-Nyhan (HGPRT)
Fabry’s (alpha-galactosidase)
PRPP Synthetase
Adenosine Deaminase
Adrenoleukodystrophy (CAT-1)
Tyrosine Kinase
CGD (NADPH-oxidase)
Hunter’s (iduronidase)
In alcoholics, what do you add to IV before administering glucose?
Thiamine! otherwise brain cells will swell and burst causing Wernicke’s encephalopathy and Wernicke’s aphasia
With GGT what is the product of this: carbon+ glutamic acid yields _______________
AA + alpha ketoglutarate
With AST what is the product of this: oxaloacetate + AA yields ___________
aspartate + carbons
With ALT what is the product of this: pyruvate + AA yields __________
alanine + carbons
What destroys all membranes?
alcohol
Why in alcoholics AST: ALT is 2:1
because the mitochondrial membrane is destroyed, both AST and GGT will leak out as well as one AST and one ALT from cell membrane, making AST:ALT 2:1 and GGT goes up
What does the COX pathway synthesize?
prostaglandins
What does the LOX pathway synthesize?
leukotreines
If you block the COX pathway which way will the pathway go?
to LOX and vice versa
5 things steroids do
IKISS
Inhibit Phospholipase A
Kills T cells and eosinophils
Inhibits macrophage migration
Stabilize mast cells
Stabilize endothelium
What does prostaglandin A2 do?
promotes platelet aggregation
What does prostaglandin E1 do?
vasodilator, keeps PDA open; Misoprostol: treatment of aspirin induced ulcers and abortifacient
Alprostadil; keeps PDA open
What does Prostaglandin E2 do?
Dinoprostone: labor induction, dilates cervix
What does Prostaglandin I2 do?
dilates pulmonary vessels; inhibits platelet aggregation
What does Prostaglandin F2 do?
responsible for dysmenorrhea (period cramps); separates placenta after fetal delivery, abundant in semen Specific PGF-2s Carboprost -abortifacient Latanoprost; –glaucoma med
Where is COX 1 found?
GI tract
Where is COX 1 and 2 found?
joints
Where is COX 2 found?
vascular endothelium
What are SRS-A (slow reacting substance of anaphylaxis)
leukotreines
Which cells make leukotreines?
mast
Which leukotreines are involved in anaphylaxis (SRS-A)?
LTC4, LTD4, LTE4
What breaks down slow reacting substance of anaphylaxis SRS-A?
aryl sulfatase
What is aryl sulfatase deficiency?
metachromatic dystrophy: ataxia, visual disturbance (bumping into furniture), learning impaired
What leukotriene along with IL-8 is a strong chemoattractant for neutrophils?
LTB-4
What is a clue for aspirin-sensitive asthma?
bronchoconstriction upon taking aspirin and nasal polyps
What is cinchonism?
thrombocytopenia, hearing loss (CN8); tinnitus
What medicine is classic for cinchonism?
aspirin
At the beginning of aspirin toxicity (within 20 min) what is the RR, pCO2, HCO3- and pH?
RR up; pCO2 down, HCO3-normal; pH high=respiratory alkalosis
between 30 - 60 minutes of aspirin toxicity?
RR up; pCO2 low, HCO3- Low, pH normal; respiratory alkalosis and metabolic acidosis
after 60 minutes GABA increases what is the RR, pCO2, HCO3-, pH
RR down; pCO2 up; HCO3-down; pH low mixed acidosis (anion gap acidosis)
Which medicine can close PDA?
IndomethiCin (C for close)
Which NSAID is topical?
Diclofenac, Ketoprofen
What is the main oral steroid?
prednisone
What is the main IV steroid?
methylprednisone
What is the DOC steroid to produce surfactant in premature delivery?
Dexamethasone
Best drug to take place of cortisol
hydrocortisol
best drug to take place of aldosterone
fludrocortisone
Which steroid is used to treat endometriosis?
Danazol (androgenic) SE: hirsutism, weight gain, insulin resistance
What is a 16 carbon fatty acid attached to C3 of G3P?
triglyceride
What is cellular marker for apoptosis?
phosphatidylserine
If an OH group is attached to C3 instead of phospate, what is it?
DAG used in IP3-DAG second messenger system
Which hypothalamic hormone does not use IP3-DAG system?
CRH
What are lacteals?
lymphatic channels for lipid absorption
Short, medium, long chain fattly acids, which first go into lacteals?
short and long
How can medium chain FA be absorbed?
attached to albumin, and can be absorbed even by IBD pts.
Which medicine blocks lateals and doesn’t allow fat absorption?
Ezetimibe
What needs CII from HDL to transport long chain fatty acids to adipose?
VLDL
Which apolipoprotein is missing in apolipoproteinemia?
Apo B48
What is the deficiency in Type 1 dyslipidemia?
lipoprotein lipase deficiency
What is the deficiency in Type 5 dyslipidemia?
lipoprotein and CII deficiency
What is the deficiency in Gaucher Disease?
Glucocerbrosidase; macrophages look like crinkled paper
What is the deficiency in Fabry’s disease?
alpha-galactosidase (X-linked recessive); cataracts; early renal failure
What is the deficiency in Krabbe’s?
beta-galactocerbrosidase causing globoid bodies (macrophages swollen with sugar)
What is the deficiency in Tay Sach’s?
Hexosaminidase A; cherry red macula, fine for first few years then regressive development
What is the deficiency in Sandhoff’s?
Hexosaminidase A and B; cherry red macula, more severe than Tay-Sach’s
What is the deficiency in Niemann-Pick?
shingomyelinase, cherry red macula, hepatosplenomegaly sets it apart from Tay Sach’s or Sandhoff’s
What is the deficiency in Matachromatic Leukodystrophy?
arylsulfatase deficiency; “childhood MS”; demyelinated plaques on LP; MRI shows demyelination
What is the deficiency in Hurler’s?
alpha L iduronidase; Gargolye features; cataracts
What is the deficiency in Hunter’s?
Iduronidase sulfatase; XL recessive, no cataracts
What is the deficiency in Metachromatic Leukodystrophy?
arylsulfatase deficiency; “childhood MS”; demyelinated plaques on LP
What enzyme do statins work on?
HMG-COA reductase
What is the remnant of VLDL and IDL?
LDL
What lipoprotein does LDL use to deposit cholesterol into tissues?
B-100
3 signs of common bile duct gallstone
pancreatitis, ALP up, WBC up and fever
What is the rate limiting enzyme for Urea cycle?
carbamoyl phosphate sythetase 1 (CPS-1)
If there is an enzyme deficiency early in the Urea cycle, what will you see in urine or plasma?
High ammonia
If there is an enzyme deficiency late in the pathway, what will you see?
serum pH is high (alkalotic); pyrimidines in the urine
MCC of liver failure?
NAFLD (alcohol #2)
Tx for liver failure
low protein diet (less than 2g/day); lactulose to flush out GI, NO fat-soluble drugs, P450 dependent drugs, benzos, barbs, GABA enhancers, alcohol
Glutamate cannot enter urea cycle, add another amine to it and turn it into glutamine to excrete in kidney, but kidney can only excrete 10%, eventually GABA rises, this is called ______
Hepatorenal Syndrome
If you want to add 1 sugar to anything what do you use?
UDP
If you want to add phospholipids what do you use?
CDP
What is the methyl donator in whole body except for nucleotides?
SAM
What is the methyl donor in nucleotides?
THF
3 ways to distinguish B12 from B9 deficiency:
B12 takes a longer time to deplete (years); B12 deficiency is associated with neuropathy; up methylmalonic acid in urine
If you want to silence DNA what enzyme can you use?
methylation (tightens DNA–methylation down with aging, more Gs and Cs)
If you want to loosen up DNA?
acetylation of histone (add A+T)
What happens to DNA upon UVB light?
form Thymidine dimers
What enzyme can snip out thymidine dimers?
UV endonuclease
What disease is associated with partial deficiency of UV light endonucleases?
Ecthyma or Ichthyosis
What disease is associated with complete deficiency of UV light endonucleases?
Xeroderma Pigmentosa
What disease is associated with too many DNA breaks from free radicals?
Ataxia Telangiectasia (spider veins, IgA def. ; malabsorption of GI
What is another name for Hereditary Non-polyposis colon cancer?
Lynch
If PRPP is high which path will it take?
De Novo, higher Km (needs more energy)
If PRPP is low which path will it take?
salvage, lower Km (needs less energy)
What is the rate limiting enzyme of Purine Pathway?
PRPP synthetase+
What three things are needed for membrane movement?
ATP,Ca, microtubules
Tx for acute gout?
indomethacin
best Tx for gout? and MOA
colchicine, blocks microtubules and interferes with cellular division and inflammatory cell mobility
best tx for gout if pt has renal failure
steroids (injected into affected joints) because indomethacin and colchicine are water soluble and toxic to kidney
best tx for chronic/recurring gout
allopurinol or Febuxostat (MOA: blocks xanthine oxidase)/ Probenicid (promotes uric acid excretion)
tx for chemotherapy pts with hyperuricemia?
fluids and allopurinol
What is the enzyme deficiency of Lesch-Nyhan Syndrome?
HGPRT deficiency; severe gout with self-mutilation
What’s the difference between uracil and thymidine?
thymidine contains a methyl group (from THF)
What does 5 Flourouracil do?
inhibits thymidylate synthetase (break down pyrimidine synthesis–CA drug)
What disease is caused by adenosine deaminase deficiency?
SCID (2/3 XL; 1/3 AR IL2, !L7 defect)
Tx for SCID
bone marrow transplant
explanation of SCID
adenosine deaminase deficiency causes dATP levels to increase–ribonucleotide reductase activity decreases–DNA syntehsis decreases–rapidly dividing cells affected most (deplete bone marrow)
Any cancer ages 0-20 are usually caused by repressor genes or enhancer genes?
repressor; K-ALLA (ALL), Rb
What enhancer mutation can cause follicular lymphoma or Burkitt’s lymphoma?
BCL2
What enhancer mutation can cause GI or Bone marrow cancers?
KRAS
What enhancer mutation can cause melanoma?
BRAF
Which ribosomes will make the proteins that stay in the cytoplasm?
free floating ribosomes
Which ribosomes make the proteins that will be secreted out of the cell?
fixed ribosomes (fixed to RER)
What is messenger RNA job?
transcribe DNA to mRNA, 3’ end poly A tail, 5’ end guanosine cap with methyl group
Which proteins are responsible for splicing out introns and bringing exons together posttranscriptionally?
SNRPs
Which RNA is used in translation?
transfer RNA
Which disease has anti-RNP?
mixed connective tissue (antibody against SNRPs)
Which enzyme replicates rRNA?
RNA polymerase I
Which enzyme helps replicate mRNA
RNA polymerase II
Which enzyme helps replicate tRNA and SNRPs?
RNA polymerase III
What is the start codon for tRNA?
AUG
What are the stop codons for tRNA?
UAA, UAG, UGA (u are away, u are gone, u go away)
Where does mRNA bind initiation factors IF-1, IF-2, IF-3 in prokaryotes? AGGAGG
Shine-Dalgarno sequence
Which antibiotic blocks initiation factors in prokaryotes?
aminoglycosides
Which two diseases are associated with EF-2 elongation?
diptheria, pseudomonas
Which antibiotics block translocase?
macrolides
Which kind of mutations often happen in diseases from birth/ early childhood?
frameshift
Which mutations are a change in one base at one point and occurs with a DNA base from same family (purine-purine) (pyrimadine-pyrimadine)?
transition mutation
Which mutations are a change in one base at one point but occurs from different DNA family? (purine –pyrimadine)
transversion mutation
Which mutation there is a change in one base but still codes for same amino acid and is asymptomatic?
silent mutation (HbC sub lysine for glutamic acid at position 6 of beta chain, asymptomatic)
What mutation changes in one base and now codes for different amino acid, i.e. in sickle cell)?
missense mutation (sickle cell, valine for glutamate)
Which mutation there is a change in one base and it becomes a stop codon?
nonsense mutation (occurs early in life)
