studystack 2 Flashcards
Amino acid catabolism produces what toxic product?
Ammonia
When does negative nitrogen balance occur?
Dietary Deficiency (starvation) Catabolic stress (ex. infection)
What 3 cofactors are required for amino acid synthesis?
Pyridoxal phosphate Tetrahydrofolate Tetrahydrobiopterin (BH4)
When pyruvate is transaminated, what does it synthesize?
Alanine
When oxaloacetate is transaminated, what does it synthesize?
Aspartate
When alpha-ketoglutarate is transaminated, what does it synthesize?
Glutamate
What forms alanine by transamination?
Pyruvate
What forms aspartate by transamination?
Oxaloacetate
What forms glutamate by transamination?
alpha-ketoglutarate
Where is arginine generated?
Urea cycle
Where does Cysteine get its S?
Methionine
What is pyridoxal phosphate (PLP) synthesized from?
Vitamin B6
What are two mechanisms through which nitrogen is removed from amino acids?
Transamination
Deamination
What enzyme is involved in the oxaloacetate –> aspartate reaction?
AST
What is the function of glutamate dehydrogenase?
It deaminates glutamate, resulting in alpha-ketoglutarate and ammonia.
Where does the deamination of glutamate by glutamate dehydrogenase take place?
Liver
What enzyme is involved in the deamination of glutamate into alpha-ketoglutarate and ammonia?
Glutamate dehydrogenase
What enzyme is involved in the conversion of glutamate + ammonium (NH4+) –> glutamine
Glutamine synthase
What conversion does glutamine synthase catalyze?
glutamate and ammonium –> glutamine
What enzyme is involved in the conversion:glutamine –> glutamate + NH4+?
Glutaminase
In the FASTED state, what do the liver and muscles contribute to amino acid metabolism?
Muscles = provide amino acids for metabolismLiver = uses lots of amino acids in fasted state.
Where does the urea cycle occur?
Liver
What is the enzyme that converts HCO3- + NH4+ –> Carbamoyl phosphate?
CPS1 (carbamoyl phosphate synthase 1)
What is the rate limiting step in the urea cycle?
CPS1 (carbamoyl phosphate synthase 1)
What is the enzyme that converts Ornithine to Citrulline?
OTC (ornithine transcarbomylase)
What is the common source of both of the N’s in urea?
Glutamate
Where do the first two steps of the urea cycle occur?
Mitochondria
In the urea cycle, after the first two steps, where do the following steps occur?
Cytoplasm
What are two products from the urea cycle?
Arginine fumarate
What is the role of NAG in the urea cycle?
It is synthesized by acetyl CoA and glutamate and it STIMULATES CPS1
Ornithine transcarbamoylase deficiency (OTC), the most common cause of urea cycle disorder, is what type of genetic trait?
x-linked
Beginning Product of FA synthesis
Citrate
Shuttle used in FA synthesis
Citrate shuttle
What cofactor is needed in all carboxylases?
Biotin
Location of FA synthesis
Hepatic cytosol
Where do we get NADPH?
Pentose Phosphate Pathway
Large complex of enzymes that binds growing acyl chain and malony CoA in first round.
Fatty Acid Synthase
What are the three types of macromolecular synthesis?
DNA replication (DNA synthesis)
Transcription (RNA synthesis)
Translation (protein synthesis)
What is the basic dogma of biology?
DNA - RNA - protein
Where does prokaryotic replication take place?
In the cytoplasm
Where does eukaryotic replication take place?
In the nucleus during S phase of the cell cycle.
Duplicate chromosomes, so that after mitosis each daughter cell will inherit a complete genome.
DNA Replication
Requirements for DNA replication
DNA polymerase, Mg2+, template, primer, and dNTPs
In what direction does DNA replication occur?
5 to 3 direction
Stage: Ribosomes assembled with mRNA between large and small subunits along with 1st aminoacyl tRNA (Met); tRNa bound to P site of ribosome.
Initiation
Where does B oxidation occur?
Mitochondria
What enzyme combines succinyl-CoA and glycine to start the Heme pathway?
ALA (aminolevulinic acid) synthetase
Rare enzyme deficiency in the heme pathway.
Porphyria
Genetic defect in UDP-glucuronyl Transferase.
Crigler-Najar syndrome
Maximum possible number of hydrogen atoms, single bonds only between carbon atoms, solid at room temperature.
Saturated fats
Has at least one double bond between carbon atoms because hydrogen atoms are missing. Double bond is point of unsaturation, they are unstable. Liquid at room temperature.
Unsaturated fats
An omega-6 fatty acid, precursor of Arachidonic acid.
Linoleic Fatty Acids
Enzyme responsible for catalyzing chain elongation in prokaryotes for both the leading and lagging strands.
DNA Polymerase III
Seals the gap that remains after Pol I removes the RNA primer and replaces it with DNA
DNA ligase
Some polymerases can copy an RNA template into DNA in the process known as ________
Reverse transcription
Hereditary nonpolyposis colorectal cancer (HNPCC), one of the most common inhereted cancers has been shown a defect in this DNA system.
Mismatch
This type of enzyme recognize a misincorporated nucleotide, nicks the strand, and remove sthe misincorporated nucleotide.
Endonucleases
Dihydrofolate reductase inhibitor
Methotrexate
Drug that induces Vitamin B6 deficiency
Isoniazid
Dietary insufficiency of thiamine/impaired intestinal absorption of B1; apathy, memory loss, nystagmus (eyeball motion)
Wernicke-Korsakoff syndrome
In infants, present as tachycardia, vomiting, convulsions, death; adults: dry skin, irritability, disorderly thinking progressive paralysis
Beriberi
Niacin defiency causes
Pellagra: dermatitis, diarrhea, dementia, death
Coenzyme in carboxylation reactions, carrier of activated CO2
Biotin
Selectively stimulates gene expression or specifically repress gene transcription, regulates plasma levels of calcium and phosphorous
Vitamin D
Post translational modification of various blood clotting factors.
Vitamin K
Active form of Vitamin E
a-tocopherol
DNA double helix that have additional twists applied to them that have coiled up upon themselves.
Supercoiling
– heterocyclic compound consisting of pyrimidine fused to a 5 member imidazole ring (adenine and guanine)
Purine
Heterocyclic compounds with nitrogen atoms at positions 1 and 3 of a 6 member ring (thymine, cytosine, uracil).
Pyrimidine
nitrogenous base (attached to 1’ C by B-N-glycosidic bond), a ribose sugar (OH at 2’ C), and a phosphate group (backbone of DNA, attached to 5’ C) – present in RNA molecules
Ribonucleotide
bond is between the 3’ OH group of the deoxyribose/ribose on the last nucleotide and the 5’-phosphate of the dNTP/NTP precurson – basically it is a bond that connects nucleotides in DNA
phosphodiester bond
Linear and single stranded, carries codon information for translation (2%)
mRNA
folded loop structures formed by intra-molecular H-bonding, carries amino acids to ribosomes (16%)
tRNA
Method: Take a single stranded DNA with gene sequence of interest with a fluorescent probe let it anneal to DNA in cell and look for fluorescence.
FISH
complex of DNA and chromosomal proteins (histones)
Chromatin
Rich in lysine and arginine, and as a result carry a positive charge. This makes it easier for negatively charged chromatin to associate.
Histones
Antibiotic drugs that interfere with DNA gyrase
Quinolone
Decondensed and transcriptionally active DNA
Euchromatin
Condensed and transcriptionally inactive DNA
Heterochromatin
Nucleotide that is an analogue of Acyclovir.
Guanine
prevent re-annealing of DNA and prevent hairpin loops from forming
SSB proteins
Drug inhibits bacterial DNA gyrase
Ciprofloxacin
Combines with certain proteins and is involved in RNA processing and gene regulation in eukaryotes
snRNA
3 stop codons
UGA, UAG, UAA
predicts the base pairing of the 5’ anticodon and 3’ codon
Wobble hypothesis
Enzyme that cleave trypsinogen to trypsin.
Enteropeptidase
Where does Urea synthesis begin and end within the cell?
Mitochondria to start, cytoplasm to finish
How much energy is required to run the urea cycle?
4 ATP
Rate limiting first enzyme for urea synthesis
carbamoyl phosphate
It can enter the TCA for energy or gluconeogenesis following urea cycle.
Fumarate
Molecular technique used to identify DNA.
Southern Blot
Molecular technique used to identify RNA.
Northern Blot
Molecular technique used to identify protein.
Western Blot
technique used to amplify DNA.
PCR
Sequence change with no phenotypic affect (i.e. 3rd base of wobbly codon, intron spliced out of message, spacer region o/s of expresed gene, similar AA w/ same effect on protein function, region of protein not critical for function - linker)
Silent mutation
Alteration of one codon, usually due to single base pair subsitution
Point mutation
Single base pair substitution altering one AA.
Missense mutation
Base pair substitution producing premature stop codon, resulting in truncated polypeptide.
Nonsense mutation
Insertion or deletion of sequence that is not a multiple of 3, so that codon reading frame is altered & random AA sequence is produced beyond the change.
Frame shift mutation
Misplacement of DNA fragment to different location of genome (different spot on same chromosome or on different chromosome)
Translocation
Deletion of part of the short arm of chromosome 5
Cri-du-chat syndrome
Removal of amino group from base by oxidation of keto group; A / C = will result in transition mutation during next round of replication; deamination of G not mutagenic, T does not have amino group to remove.
Deamination
DNA polymerase proofreading, ligation of strand breaks, direct base repair, excision repair.
DNA repair mechanisms
Product of defective UV specific endonuclease; results in extensive skin tumors after exposure to sunlight
Xeroderma pigmentosum
Most common conformation of DNA
B form
2nd most abundant class of chromatin proteins.
Scaffold proteins
Vitamin A derived from animals provide retinyl esters at are readily digested & absorbed as
Retinol
First detectable sign of a vitamin A deficiency
Nyctalopia
How many carbons does palmitic fatty acid have?
16
How many carbons does stearic fatty acid have?
18
How many carbons does oleic fatty acid have?
18
What makes up a triaclglycerol?
A glycerol and 3 fatty acids
genetically defective LDL receptors occur and LDL levels become extremely high
Familial Hypercholestemia
There is a mutation in the nucleotide excision repair enzymes. Individuals with this genetic defect are unable to repair thymine dimers.
Xeroderma pigmentosum
Excess NADH in the fed state will inhibit _______ in the Kreb cycle
isocitrate dehydrogenase
Inhibition of isocitrate dehydrogenase causes a build up of ____________.
Citrate
FA synthesis is induced by _____________.
Insulin
Inhibits carnitine trasport of fatty acyl groups into the mitochondrion.
Malonyl CoA
Lipoprotein lipase synthesis and secretion is induced by ____________.
Insulin
2 types of sphingolipid
Sphingomyelin & Glycosphingolipids
sphingosine (18C palmitate) connected by amide (serine) linkage to long chain fatty acid
Sphingolipids
Where does the 5th step of sphingolipid synthesis occur?
Golgi
Where do steps 1-4 of sphingolipid synthesis occur?
ER
What are the most abundant gangliosides in myelin?
Cerebrosides
What lipid disease involves the lipid gal-gal-glucosylceramide (ganglioside) due to deficient enzyme alpha-galactosidase?
Fabry’s
What lipid disease involves the lipid glucosylceramide (cerebroside) due to deficient enzyme beta-glucosidase?
Gaucher’s
What lipid disease involves the lipid sphingomyelin (sphingolipid) due to deficient enzyme sphingomyelinase?
Niemann-Pick
What lipid disease involves the lipid GM2 ganglioside (ganglioside) due to deficient enzyme hexosaminidase A?
Tay-Sachs
Where are sphingolipids destroyed?
Lysosomes
What kind of linkage joins the amino acid to the tRNA molecule?
Ester
upstream sequence to a start codon that can base pair to 3’ end of 16S RNA
Shine-Dalgarno sequence
Patient with Hepititis A has what type of elevated bilirubin levels?
Indirect Bilirubin
Defect in a transporter for cysteine and basic AA that results in kidney stones
Cystinurea
Catalyzes transamination
aminotransferases
ApoB 100 is attached to which lipoproteins?
LDL, IDL and VLDL
ApoB48 is attached to which lipoprotein
Chylomicrons
Major component of membrane lipids. Analogue of plasmalogen in heart.
Phospatidylcholine
Major component of membrane lipids. Analogue of plasmalogen in nerve tissue.
Phospatidylethanolamine
Used to form PIP2 which is cleave by phospholipase C to DAG and IP3 in Ca2+ second messenger system.
Phospatidylinositol
Glycerol from fatty acids (after fatty acid metabolism) is converted into DHAP in the liver to go back into glycolysis or gluconeogenesis
DHAP
Lipase that releases fatty acids from fat (activated by PKA via adenyl cyclase).
Hormone Sensitive Lipase
Soluble mixed balls of fat that are created in order to bring fat to the intestinal lining of the small intestine (enterocytes) in order for fat to be re-absorbed, and then they are reabsorbed
Micelles
Pyrimidines
Cytosine, Thymine (DNA) and Uracil (RNA)
Percentage of A=T and G=C
Chargaff’s Rules
Where are very long chain fatty acids degraded?
peroxisomes
directs circulating lipoproteins to their destinations
apolipoproteins
most circulating cholesterol found
LDL
acts on chylomicrons in the capillaries
lipoprotein lipase
Most common familial dyslipidemia
Type 2a hypercholesterolemia
Increased IDL, VLDL, chylomicrons; increased risk of atherosclerosis
Type 3 hyperlipoproteinemia
Lipoprotein lipase deficiency
Type 1 hyperchylomicronemia
Altered apolipoprotein C-II
Type 1 hyperchylomicronemia
Pancreatitis, HSM, eruptive xanthomas, abdominal pain after fatty meals; may lead to retinal vein occlusion
Type 1 hyperchylomicronemia
Increased LDL & cholesterol; increased risk of atherosclerosis
Type 2a hypercholesterolemia
LDL receptor deficiency
Type 2a hypercholesterolemia
Autosomal dominant; corneal arcus, tendon xanthoma, xanthelasma
Type 2a hypercholesterolemia
Increased triglycerides, cholesterol, chylomicrons; no increased risk of atherosclerosis
Type 1 hyperchylomicronemia
Increased VLDL & triglycerides
Type 4 hypertriglyceridemia
Hepatic overproduction of VLDL; pancreatitis
Type 4 hypertriglyceridemia
ApoE3/ApoE4 defect
Type 3 hyperlipoproteinemia
Autosomal dominance (late onset), CAG repeats in the coding section (encoded bc of strand slippage during replication)
Huntington
deficiency –> Lesch Nyan, X-linked recessive
HGPRT
used in purine salvage pathway, causes SCID, ATP and dATP accumulate –> imbalnce of nucleotide pool, prevents DNA synthesis
Adenosine deaminase deficiency
suicide inhibitor of xanthine OXIDASE, enzyme can’t degrade purines to urate
Allopurinol
hemoglobin’s oxygen binding affinity is inversely related both to acidity and to the concentration of carbon dioxide.
Bohr effect
It is an inducer, inducer presented to the cell is 1, 6 Allolactose. It has a regulator gene and structural gene
Lactose Operon
elaborates mRNA referred to as imRNA which is responsible for the synthesis of a transcription factor that acts as a repressor
i gene
Name 3 diseases related to CAG expansion
Huntington, Kennedy and SC Ataxia
Inherited mental retardation, CGG repeat at 5’ UTR, FMR1 gene that encodes a RNA binding gene. Over 200 repeats no transcription of FMR1
Fragile X syndrome
explains why the third base in a codon may differ and be recognised by the same tRNA and therefore code for the same amino acid. The wobble hypothesis states that the first and second bases must pair in the watson-crick manner but 3rd less constrained
wobble hypothesis
Promoter site in prokaryotes
pribnow box (tataat)
major phospholipid and surfaceactivecomponent of surfactant
Dipalmitoylphosphatidylcholine (DPPC)is the major phospholipid and surfaceactivecomponent of surfactant.
glycerophospholipid serves as a substrate for LCAT
Phosphatidylcholine
What is the precursor of all glycerophospholipids?
Phosphatidic acid
Severely impaired or absent glucronyltransferase activity -Uncommon -Severity depends on how much activity remains -Type I, severe defect leads to kernicterus & death if untreated -Type II, less severe defect
Crigler-Najjar syndrome
Mildly reduced expression of glucuronyltransferase -Very Common (estimated 3-7% of US Pop.) -Results in slightly elevated bilirubin levels but no detrimental health effects -May have increased sensitivity to certain drugs
Gilbert’s syndrome
Very complex synthetic pathway where N-linked (usually to Asp) or O-linked (usually Ser or Thr) glycosidic bonds
Glycoproteins
Their synthesis is very complex -Turn over by shedding from the cell surface and by endocytosis (broken down in lysozomes) -Can be extracellular or attached to the membrane
Proteoglycans
a disease that results when there is a deficiency in the enzyme that phosporylates mannose residues
I-cell disease
-Lysosomal enzymes get secreted -lysosomes don’t have the full complement of required enzymes so proteins build up in them (inclusions) -Extremely rare
Ceramide + UDP-Glucose
Glucocerebroside
Ceramide + UDP-Galactose
Galactocerebrosides
Ceramide + 2 or more UDP-sugars and N-acetylneuraminic acid (NANA)
Ganglioside
deficiency of enzymes that breakdown GAG fragments, thus they accumulate in the lysosomes -can cause a variety of problems such as skeletal deformities and mental retardation
mucopolysaccharidoses
a deficiency in an enzyme that results in an accumulation of sphingolipids in the lysosomes -Fabry disease is x-linked, others are autosomal recessive
sphingolipidosis
What happens to acetoacetate when it remains in the blood stream?
converted non-enzymatically to acetone
Alternative route for metabolism of glucose
Pentose Phosphate Pathway
PPP leads to the synthesis of —– for nucleotide and nucleic acid formation
Ribose
Main hexoses that are absorbed from GI tract
Glucose, fructose and galactose
First enzyme of PPP
Glucose 6 Phosphate Dehydrogenase
Deficiency to glucose 6 phosphate dehydrogenase will yield to acute hemolysis of RBC leading to
Hemolytic anemia
The oxidative phase of PPP generates
NADPH
ransketolase requires what coenzyme
Thiamine
Reduced glutathione removes H2O2 in a reaction catalyzed by
Glutathione peroxidase
An enzyme found in the liver which also functions in glycolysis in the liver by cleaving fructose 1,6 bisphosphate
Aldolase B
CCA at 3’. Adaptor molecule, 2 ends are anchoring the AA at the 3’ end & at other end there is anticodon loop which interacts with mRNA. 5’ loop=di-hydrouridine. 3’ loop=T-psuedouridine C loop
tRNA
Requires EF-G & GTP. 1st aminoacyl tRNA gets ejected from P site to E site.
Translocation
Sequence of AA residues that is highly enriched in hydrophobic amino acid residues.
Signal peptide
Site of production of chylomicron
Small intestines
Transport of cholesterol from liver to tissues
VLDL and LDL
Transport of cholesterol from tissues to liver (reverse transport)
HDL
Transport of cholesterol from intestine to liver
Chylomicrons
Toxicity: cleft palate, diarrhea, bone resorption, headache, nausea, aplopecia, hepatomegalia
Vit A
Deficiency: hemorrhaging, stomach pain, bone malformation, deposits of Ca2+ in arteries
Vit K
Function: Antioxidant, Radical Scavenger
Vit E
What are the tissue sites for production of adrenal steroids?
zona glomerulosa (aldosterone)
zona fasciculata (cortisol)
zona reticularis (DHEA & androstenedione)
What type of steroid is aldosterone?
mineralocorticoid
What type of steroid is cortisol?
glucocorticoid
14 subunits, nucleolus, produces rRNA precursors, resistant to inhibition by alpha-amanitin.
RNA polymerase I
12 subunits, nucleus, precursor to mRNA, sensitive to alpha-amanitin
RNA polymerase II
17 subunits, nucleus, synthesizes 5SrRNA, tRNA & small RNAs, moderated sensitivity to alpha-amanitin
RNA polymerase III
What effect does fasting have on HMG-CoA reductase?
decreases activity
What effects do insulin and thyroxin have on HMG-CoA reductase?
increase activity
What is the committed step in cholesterol synthesis?
HMG-CoA reductase
What receptor in the liver endocytoses chylomicrons?
Hepatic Apo-E receptor
What disease boasts defective Apo-B100/E receptors?
familial hypercholesterolemia
What 2 enzymes does HDL donate to maturing chylomicrons and VLDLs?
ApoCII and ApoE
activates lipoprotein lipase
Apo CII
What is the committed step in the synthesis of bile salts?
7-alpha-hydroxylase
a rare disorder caused by defective Cys2 carrier across lysosomal membranes
cystinosis
Impaired transport of neutral AAs across intestinal and renal epithelial cells
Hartnup disease
lack of homogentisate oxidase involved in the catabolism of Tyr
Alkaptonuria
