Biochemistry Flashcards
Three enzymes that use thiamine as a cofactor
Pyruvate dehydrogenase
alpha-ketoglutarate dehydrogenase
Transketolase
What is the role of a glycosylase in base excision repair?
Recognizes and cleaves abnormal bases
What is the role of a lyase in base excision repair?
Completes extraction of the AP site (following endonuclease enzymatic chewing)
What are the fates of pyruvate in the presence of O2 vs with insufficient oxygen
O2: pyruvate dehydrogenase converts pyruvate to acetyl-CoA
Limited O2: lactate dehydrogenase converts pyruvate to lactate
Are eukaryotic or prokaryotic mRNA polycistronic?
Prokaryotic mRNA is polycistronic
Eukaryotic mRNA is rarely polycistronic
What is the role of ornithine?
Ornithine combines with carbamoyl phosphate to become citrulline- part of the urea cycle to eliminate urea
What provides the rubber-like properties of elastin?
Extensive cross-linking between elastin monomers, which is facilitated by lysyl oxidase (between lysine residues)
Where does early onset emphysema first appear in people with alpha-1-antitrypsin deficiencies?
Early onset, lower-lobe predominant emphysema
What causes the formation of brown stones in the gallbladder?
Brown pigment stones arise secondary to bacterial or helminthic infections which leads to the release of beta-glucoronidase.
Beta-glucuronidase hydrolyzes bilirubin glucuronides and increases the amount of unconjugated bilirubin.
The liver fluke chlornochis sinensis cause also cause this
Which is the enzyme responsible for Pompe’s disease?
Acid maltase/alpha-glucosidase in lysosomes
High levels of neutral amino acids is indicative of which disease?
Hartnup disease
What are the findings of hartnup disease?
Impaired transport of neutral amino acids in the small intestine and proximal tubule of the kidney–> pellegara like skin eruptions, and cerebellar ataxia, which occurs as a results of niacin deficiency (derived from tryptophan)
How can you treat Hartnup disease
High protein diet (since many amino acids aren’t being absorbed) and supplimentary niacin (derived from tryptophan, which isn’t being absorbed properly)
Which substance directly stimulates the conversion of pyruvate to phosphoenolpyruvate in gluconeogenesis?
Acetyl CoA
Levels are high in the presence of fatty acid oxidation
How does pyruvate kinase deficiency lead to splenomegaly and anemia?
RBCs don’t have any mitochondria and rely of glycolysis for ATP production
Low pyruvate –> insufficient membrane integrity and inability to maintain erythrocyte structure.
RBCs are eaten up in the red pulp –> red pulp hyperplasia
Pyridoxine (B6) is a cofactor in which type of reactions?
Transamination and decarboxylation of amino acids
How does decreased bile acid synthesis lead to cholesterol stones?
Bile acids make cholesterol more soluble.
Low bile –> favors cholesterol gallstone formation
What is alkaptonuria?
Relatively benign childhood disorder –> severe arthritis as an adult
Deficiency of homogentisic acid dioxygenase
Accumulation of homogentisic acid –> blue/black deposits, urine turns black when exposed to air
Failure of what process leads to ehlers danlos?
Failure of cleavage of terminal propeptides in the extracellular space
Which are the two exclusively ketogenic amino acids?
Lysine and Leucine.
Use in someone with pyruvate dehydrogenase deficiency to avoid lactate build up
Babies with maple syrup urine disease may improve with which suppliment?
Thiamine
What is the MOA leading to maple syrup urine disease?
Inability to break down branched chain amino acids
What are the symptoms of wet beriberi?
symmetrical peripheral neuropathy
Wet beriberi includes cardiac involvements
Musty body odor= which inborn error of metabolism?
PKU
Phenylalanine is not converted to tyrosine
Which amino acid is the precursor for melanin?
Tyrosine
What is the enzyme phenylethanolamine-N-methyltransferase responsible for?
Conversion of NE to Epi
Starting from tyrosine, get to epinephrine
tyrosine –> dopa –> Dopamine –> NE –> Epi
also, phenylalanine –> tryosine
Where in the cell does heme synthesis occur?
Partly in the cytoplasm, partly in the mitochondria
FAD acts as an electron acceptor for which enzyme in the TCA cycle?
Succinate dehydrogenase
Name the two methods by which the lac operon is regulated
Positive regulation: cAMP-Cap binds upstream of the promoter region
Negative regulation: the repressor binds to the operator
Name the inborn error of metabolism that causes urine to turn black overnight?
Alkaptonuria
What is the defective enzyme in alkaptonuria? What conversion is inhibited?
Homogentisic acid dioxygenase is deficient
Impairs the conversion of tyrosine –> –> –> fumarate
Which monosaccharide enters glycolysis after the rate limiting step (bypasses PFK-1) and therefore is most rapidly metabolized?
Fructose
How does fructose enter glycolysis?
Fructose is converted to fructose-1-phosphate by fructokinase.
Fructose-1-phosphate is converted to DHAP and glyceraldehyde by aldolase B
Glyceraldehyde is converted to glyceraldehyde 3 phosphate by triokinase which enters the glycolytic pathway
What type of poisoning leads to cholinergic excess?
Poisoning with organophosphates (used in agriculture). They act as cholinesterase inhibitors
Treat with atropine and 2PAM
Why does septic shock cause lactic acidosis?
Septic shock leads to poor tissue perfusion and therefore oxidative phosphorylation is shut down. Anaerobic metabolism occurs.
What are “dependent locations” in the lungs, as seen in aspiration pneumonia?
The posterior segments of upper lobes and superior segments of lower lobes are dependent and commonly affected by aspiration pneumonia. They are dependent on the patient laying supine.
What is the treatment for cyanide poisoning? How does it work?
Inhaled amyl nitrite.
The nitrites oxidize the iron in Hb to methemoglobin (3+), which has a higher affinity for CN- . CN- binds to the ferric iron more avidly than the mitochondrial enzymes —> diminishes the toxic effect
Where are cytoplasmic P bodies located?
Cytoplasm
They are responsible for mRNA translation regulation and mRNA degradation
What two things are produced by the pentose phosphate pathway?
NADPH- for use in reductive reactions
Ribose-5-phosphate- a precursor for the synthesis of nucleotides
What enzyme converts alpha-ketoglutarate to succinyl-CoA? Why is this enzyme particularly susceptible to inhibition in an alcoholic?
alpha-ketoglutarate dehydrogenase
This enzyme requires both NAD+ and thiamine for the reaction to proceed.
Ethanol metabolism increases the NADH/NAD+ ratio, and alcoholics are thiamine deficient
Vitamin B12 is a cofactor for which two enzymes?
methylmalonyl-CoA mutase- converts methylmalonyl-CoA to succinyl-CoA
Methionine Synthase- converts homocysteine and folic acid to methionine
Explain the pathology behind maturity-onset diabetes of the young
Glucokinase deficiency
Functions as the glucose sensor in beta cells by varying the rate of entry into the glycolytic pathway based on blood glucose levels.
Deficiency –> less ATP and lower insulin secretion
Erythrocytosis is a sequelae of what type of shift in the O2 saturation curve?
Left shift–
Causes lower O2 delivery to the peripheral tissues
Deficiency in uridine monophosphate (UMP) synthase leads to which disease?
Orotic aciduria
Supplement with uridine
What are the cardiovascular sequelae of homocystinuria? Why?
Hypercoagulability and thromboembolic events. Homocysteine is prothrombotic
How is methionine connected to cysteine levels?
If a patient has homocystinuria, they most commonly have a defect in cynthathinoe synthase. This prevents the conversion of homocysteine to cysteine, and will result in increased methionine levels in the blood as well, as homocysteine is converted to methionine
Which DNA polymerase possesses 3’-5’ exonuclease activity?
All DNA polymerases. It enables them to identify and remove mismatched bases – proofreading capability
Only DNA polymerase III also has 5’-3’ exonuclease activity which allows them to remove the RNA primer and replace it with DNA
