Biochem Flashcards by Krupa Harishankar

In what reactions is thiamine a cofactor?

1) Pyruvate dehydrogenase (Krebs pyr > acetyl coA)
2) a-ketoglutarate dehydrogenase (TCA and branched chain aa catabolism)
3) Transketolase (HMP shunt pentose > glyceraldehyde 3P)

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What is the Rx for thiamine deficiency?

Glucose + thiamine infusion

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What confirms thiamine deficiency?

Increased erythrocyte transketolase post infusion

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What is the genetic basis of Fragile X?

200 + CGG repeats on FMR1 gene (located on X chromo)

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What is the pathogenesis of Fragile X?

Increased repeats causes hypermethylation

- Inactivates the gene

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What are the symptoms of Fragile X?

Mental retardation, messed up face, macroorchidism

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What steps must occur for mRNA translation to begin?

mRNA binds 16S (part of 30S complex)
50S joins
Translation begins

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What is the function of 3-5 exonuclease?

Proofreading

proofread the opposite way of synth to check

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What is the function of 5-3 exonuclease?

Allows replacement of nts in repair

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What histones make up the nucleosome core?

H2A, H2B, H3, H4

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What histone binds DNA between histone cores to facilitate compact packaging?

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What is the fx of N-acetylglutamate?

Activates carbamoyl phosphate synthase, the enzyme required for the first rxn of the UREA CYCLE

CO2 + NH4 > carbamoyl phosphate

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What are the components of N-acetylglutamate?

Acetyl coA and glutamate

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What is heteroplasmy?

Mixture of 2 types of genetic material, as in mitochondrial inheritance (randomly distributed in mitosis)

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What are 3 mitochondrial diseases with penetrance based on heteroplasmy?

LHON: Leber’s Hereditary Optic Neuropathy

MERF: Myoclonic Epilepsy with Ragged Fibers

MELAS: Mito. Encephalomyopathy with Lactic Acidosis and Stroke-like episodes

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Lysosomal storage disease:

AR lack of sphingomyelinase
Sphingomyelin buildup in CNS

Niemann Pick

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Lysosomal storage disease:

Foamy histocytes in liver, spleen skin
"Lipid laden macrophages"
HSM
Cherry red spot on macula
Death by 3 years

Niemann Pick

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Lysosomal storage disease:

AR lack of hexosaminidase A
Accumulation of GM2 ganglioside

Tay Sachs

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Lysosomal storage disease:

“Onion skin” lysosomes
Neural degeneration
Cherry red spot on macula
Normal development 2-6 mo, then sxs

Tay Sachs

Note: no HSM, unlike NP

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Lysosomal storage disease:

AR lack of glucocerebrosidase
Accumulate glucocerebroside

Gaucher

Rx: recombinant glucocerebrosidase (this one is treatable!)

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Lysosomal storage disease:

Wrinkled paper-like macros
HSM
Anemia
Thrombocytopenia
Bleeding
Osteopenia
Bone pain
Fractures

Gaucher

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Lysosomal storage disease:

XR lack of alpha galactosidase A
Build up ceramide trihexoside

Fabry

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Lysosomal storage disease:

Peripheral neuropathy of hands and feet
Angiokeratomas
Cardiovascular/renal disease

Fabry

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Lysosomal storage disease:

AR lack of arysulfatase A
Build up cerebroside sulfate

Metachromatic Luekodystrophy

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Lysosomal storage disease: Central and peripheral demyelination Ataxia Dementia

Metachromatic Leukodystrophy

Lysosomal storage disease: | AR lack of Galactocerebrosidase Build up Galctocerebroside, psychosine

Krabbe

Lysosomal storage disease: Peripheral neuropathy Developmental delay Optic atrophy Globoid cells

Krabbe

Lysosomal storage disease: | AR lack of alpha-L-iduronidase Build up heparan sulfate, dermatan sulfate

Hurler

Lysosomal storage disease: ``` Developmental delay Gargoylism Airway obstruction Corneal clouding HSM ```

Hurler

Lysosomal storage disease: | XR lack of Iduronate sulfatase Build up heparan sulfate, dermatan sulfate

Hunter

Lysosomal storage disease: Mild Hurler + aggressive behavior No corneal clouding

Hunter

What 2 lysosomal storage diseases are XR?

Fabry and Hunter

What is impaired in peroxisomal diseases?

Cannot break to VLCFA and some branched chain FA | Build up Phytanic Acid

What is the defect in Zellweger syndrome?

Peroxisomal disease | Cannot make myelin

What is the defect in Refsum sundrome?

Defect in peroxisomal a-oxidation

What is the cofactor in decarboxylation and transamination reactions?

What is the rate limiting step in the Urea Cycle?

Carbamoyl phosphate synthase

What is the most common Urea Cycle defect?

Ornithine transcarbamoylase

Which bacterial DNA polymerase has 5-3 exonuclease?

DNA Pol I | - Used to excise RNA primer

If an amino acid's pKa > pH, then the amino acid exists in the (protonated/uprotonated) form?

Protonated | It's above it's comfort zone, so it takes an H no prob

Carnitine deficiency causes:

Inability to move acyl coA into the mitochondria for FA oxidation Myoglobinemia Weakness post exercise Increased muscle TGs Hypoketonimia

Acyl coA dehydrogenase deficiency causes:

Impaired beta-oxidation of FA Hypoglycemia Hypoketonemia

Precursor to FMN and FAD

Riboflavin

Coenzyme for succinyl dehydrogenase (succinate > fumarate rxn)

FAD, from B2/riboflavin

Where does VLCFA oxidation occur?

Peroxisomes (not mito!)

What is the role of cytoplasmicP bodies?

mRNA regulation and turnover

If free energy of products is less than substrates, G is negative and rxn favors:

products

If free energy of products is greater than substrates, G is positive and rxn favors:

substrates

What is the GTP producing step of the Kreb's Cycle?

Succinyl-coA to Succinate This is substrate level phosphorylation, not ox phos

What vitamin is contraidincated in pregnancy?

Vitamin A --teratogen!

What are the effects of Vitamin A on pregnancy?

``` Microcephaly Cardiac abnormalities Early epiphyseal closure Growth retardation Spontaneous abortion ```

What is the major aa that transfers nitrogen to the liver for disposal?

Alanine | aLa to the Liver

Amino groups transferred to a-ketoglutarate form:

Glutamate

Glutamate processed in the liver forms:

Urea, which is then disposed

Impact of Fructose 2,6 Bisphosphonate on glycolysis:

Activates glycolysis by increasing Phosphofructokinase-1 Inhibits gluconeogenesis by inhibiting Fructose 1, 6 Bis

What determines resting membrane potential?

The ions most permeable to the membrane | - Generally K+ and Na+ > - 70 mV

Biotin is a cofactor to what kind of rxns?

Carboxylation | Tin race Car with number 7 painted on the side

Biotin is a cofactor what specific rxns:

1. Acetyl coA carboxylase 2. Pyruvate carboxylase (pyr > oxaloacetate) 3. Propionyl carboxylase 4. b-methacronoyl carboxylase All involved in carb and lipid metabolism

Pyridoxine is a cofactor for what kinds of rxns?

Transamination and DEcarboxylation rxns with aas

Why does B12 deficiency produce MMA?

B12 is cofactor in isomerization rxn that transforms MM coA to succinyl coA (before entering Kreb's Cycle)

Small circular DNA in eukaryotic cells that is maternally derived

Mitochondrial DNA

Function of glycerol kinase:

Converts glycerol to G3P in the liver

Uses of glycerol by the liver:

1. Triacylglycerol synth 2. Gluconeogenesis 3. Intermidate in glycolysis

What deficiency causes propionyl acidemia?

Propionyl coA carboxylase | Propionyl coA > MM coA

What is propionyl derived from?

Metabolism of branched chain aas, odd numbered FAs, and cholesterol side chains

What enzymes are produced in the SER?

Steroid and phospholipid biosynthesis All steroid producting cells (adrenals, gonads, liver) contain abundant SER

What enzymes are produced in the RER?

Secretory, lysosomal, and membrane proteins

What is the fx of Vitamin E?

Vitamin E is an antioxidant Lack = increased susceptibility of neuron and erythrocyte membranes to oxidative stress, increased FA oxidation

What are the CNS sx of Vitamin E deficiency?

Loss of vibration and proprioception due to dorsal column and spinocerebellar tract = ataxia

What enzyme is missing in Classic Galactosemia?

Galactose uridyl transferase (FAB GUT)

Short term presentation of Galactosemia

Vomiting after breast feeding, lethargy | Decreased glucose in blood after mlik

Long term presentation of Galactosemia

Galactitol in lens and liver, permanent damage

What enzyme is missing in Alkaptonuria?

Homogentisate Oxidase

What rxn does homogentisate oxidase perform?

Tyr > fumarate

Where does homogentisic acid accumulate?

Urine, tendons/cartilage, ears, nose, cheeks > black pigment

What is pantothenic acid?

B5 = coA

What does RNA pol I make?

18S, 5.8S, ad 28S ribosomal units

What does RNA pol II make?

mRNA (proteins) snRNA (splicing) micro RNA (silencing)

What does RNA pol III make?

tRNA (link codons to aas) | 5S ribosomal unit (component of 60S)

What is palmitoylation?

Anchoring of GPCRs to plasma membrane Attaches FA of the GPCR to a cysteine of the PM

N-terminal hydrophobic residues serve as:

Signal peptides: stop translation in the cyto and target to RER

What is the x intercept on a Lineweaver Burke plot?

1/Km

What is the y intercept on a Lineweaver Burke plot?

I/Vmax

DNA methylation does what to transcription?

Silences

Area of DNA rich in CG repeats means it's...

methylated, and silenced.

What is the cause of cell swelling after injury?

Buildup of Na because of lack of Na/K ATPase (no ATP)

What are the sx of abetalipoproteinemia? | Fat Betting Pirate says AAR

1. Fat buildup 2. a-Beta 3. Pigmented retinopathy (can't see in low light) 4. Acanthocytes 5. Ataxia 6. Retardation

Rx for methanol poisoning:

Ethanol or Fomepizole

What is the MOA of ethanol or fomepizole in methanol poisoning?

Inhibit alcohol dehydrogenase and prevent buildup of formaldyehyde and formic acid

What happens in a lack of myeloperoxidase?

Less respiratory burst to kill bacteria | Less hydroxyl halide (HOCl-) from H2O2

Muscle weakness, lack of proprioception, and retinal damage are signs of what vitamin def?

What are secondary structures of proteins, and what type of bond is responsible?

alpha helix, beta sheet, H bonds

What bonds are responsible for the tertiary structures of proteins?

Ionic bonds

What is the order of proteins at work in base excision repair?

1. Glycosylase 2. Endonuclease 3. Lyase 4. Polymerase 5. Ligase

What types of corrections does base excision repair make?

Corrects single base DNA defects induced spontaneously or by exogenous chemicals

Megalobastic anemia Neuro abnormalities Growth retardation Orotic acid in urine Diagnosis?

Orotic aciduria

What is the disorder underlying orotic aciduria?

Pyrimidine metabolism

What is the Rx for orotic aciduria?

Uridine, to feedback inhibit carbamoyl phosphate synthase II

What are TATA and CAAT boxes?

Promoters of transcription in eukaryotic cells 25-80 bases upstream of start site Serve as binding site for RNA pol II, aka "transcription initiation sites"

What are 3 DNA binding protein domains?

Leucine Zipper Helix-loop-helix Zinc Finger

Where in the cell does purine/pyrimidine synth take place?

Cytosol

What are some hydrophobic aa?

Val, ala, isoleucine, met, phe - These are often transmembrane domains of proteins