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MCM final > protein sorting/post translational mod. & hematopoiesis > Flashcards

protein sorting/post translational mod. & hematopoiesis Flashcards

1
Q

Secretory vesicles contain which molecules destined for secretion outside the cell?

A

Gastric acid Digestive enzymes Lung surfactants’ Sebum

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2
Q

Extracellular vesicles can carry protein and nucleic acids. what are they used for?

A

cell signaling. They are also linked to metastatic cancers.

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3
Q

How does a protein get into the mito?

A

Tom/Tim23 complex!

Once its in, the signal sequence is cleaved and protein is mature.

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4
Q

Protein kinases include…………….

They recognize consensus sequences, can phosphorylate multiple substrates, and can phosphorylate single or multiple amino acids.

A

tyrosine kinases or serine/threonine kinases

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5
Q

Chronic myelogenous leukaemiais a slow-growing cancer of the blood-forming tissue (bone marrow) leading to the production of too many white blood cells. It is caused by a rearrangement (translocation) of genetic material and fuses a part of the ABL1 gene from chromosome 9 with part of the BCR gene on chromosome 22, creating an abnormal fusion gene called BCR-ABL1.

The product of ABL1 gene is what?

A

a protooncogene tyrosine protein kinase.

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6
Q

What are the two types of ubiquitination?

A

– Monoubiquitination: involved in DNA repair, regulation of transcriptionand internalization of transmembrane proteins.

– Polyubiquitination: involved in proteosomal degradation of modified protein, endocytic trafficking and inflammation.

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7
Q

Ubiquitination requires what three types of enzymes?

A

ubiquitin-activating (E1), ubiquitin-conjugating (Ubc), and ubiquitin ligase (E3).

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8
Q

What are the 2 ubiquitination diseases we talk about?

A
  • Renal cell carcinoma (involving Von-Hippel-Lindau gene which encodes E3 ubiquitin ligase)
  • Breast cancer (involves BRCA1, which is human tumor suppressor gene. It has E3 ubiquitin ligase activity. Mutation that affects the ubiquitin ligase function are found in various cancers.)
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9
Q

Is acetylation spontaneous or is it catalyzed by acetyltransferases?

A

Can be either!

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10
Q

One example of acetylation is acetylation of………….. by asprin.

A

Cox1/Cox2

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11
Q

The most common protein acetylation occurs at what residues?

A

lys

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12
Q

………… of tumor suppressor p53 is necessary for its activation.

A

Acetylation

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13
Q

The addition of a methyl group usually occurs on the nitrogen side-chain of what aa’s?

A

lysine or arginine

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14
Q

Histone methylation is catalyzed by histone methyltransferase. what serves as a donor of methyl group?

A

S-adenosylmethionine (SAM)

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15
Q

Histone methylation can be associated with transcriptional repression or activation. For example, Trimethylation of histone H3 at……….. is an active mark for transcription. Dimethylation of histone H3 at………….. is a signal for transcriptional silencing.

A

Lys 4

Lys 9

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16
Q

Hydroxylation most frequently occurs at…………… residue.

A

proline

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17
Q

What modification is important in stabilizing collagen? What enzyme is used?

A

Hydroxylation with prolyl 4-hydroxylase

–This reaction requires iron and α-ketoglutarateto carry out the oxidation.

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18
Q

……………. deficiency can lead to less stable collagen, which can manifest itself as the disease scurvy.

A

Vitamin C

* Vitamin C is necessary to return the iron to its oxidized state.

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19
Q

Carboxylation is a posttranslational modification of glutamate (Glu) residues, to γ-carboxyglutamate, in proteins. Carboxylation occurs in the liver and is performed by γ-glutamyl carboxylase. What vitamin is required as a cofactor?

A

Vitamin K

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20
Q

Carboxylation occurs primarily in proteins involved in the blood clotting cascade. Mutations in the gene for…………………… are associated with multiple coagulation factor deficiency.

A

γ-glutamyl carboxylase

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21
Q

γ-carboxyglutamate binds…………, which is essential for its function.

A

Ca++

22
Q

GPI-anchored proteins are co-translationally inserted into the ER membrane. The hydrophobic C-terminus is cleaved off and replaced with a GPI-anchor by GPI-transamidase. The GPI-protein is translocated to Golgi and then to the plasma membrane. GPI-anchored proteins can be what?

A

* Antigens (human carcinoembryonic antigen (CEA) is used as a cancer marker.

* Enzymes (alkaline phosphatases and acetylcholinesterase)

23
Q

The GPI-anchored proteins on the surface of RBCs protect them from destruction by the complement system.

Somatic mutations in the X-chromosomal gene PIGA, which is an essential component of GPI-transamidase, is the most common cause of…………………………

A

paroxysmal nocturnal hemoglobinuria (PNH).

24
Q

What can use glycosylation to shield from immune recognition?

A

Viruses

25
Q

Glycosylation vs glycation

A

* Glycosylation is a covalent attachment of carbohydrate to the target molecule.

* Glycation is a non-enzymatic covalent attachment of carbohydrate to Arg or Lys of the target molecule.

26
Q

Glycation reactions are very slow and occur mainly in the bloodstream. They result in the formation of advanced glycation end products (AGEs). When do AGEs form?

A

In hyperglycemic conditions and/or the natural process of aging.

27
Q

………….. is often used to improve the color, flavor, aroma, and texture of foods. A significant generation of AGEs occurs when sugars are cooked with proteins. It has been reported that, in renal failure patients, there was a 29% increase in glycation levels in the blood of those subjected to an AGE-rich diet!

A

glycation

28
Q

The measurement of………. hemoglobin (HbA1c) levels is used to monitor diabetes.

A

glycated

29
Q

During erethropoesis (RBC development) how does the cell shape change?

A

As cell matures, it gets smaller, and the nucleus gets smaller (so more cytoplasm present in matured cells)

30
Q

What controls the rate of erythropoiesis?

A

Oxygen content of the blood.

hypoxia –> increased # of erythrocytes released from the bone marrow

31
Q

Erethropoietin Is a glycoprotein produced primarily in the kidney and transported to the bone marrow by the bloodstream. Decrease in pO2 stimulates erythropoietin production. How does it compensate for hypoxia?

A

–Increasing mitotic activity of precursor erythrocytes

–Results in shortening of generation time of precursors

–Promotes early release of reticulocytes

32
Q

When a RBC is made, what are the different erythrocytic cells, in order of less mature to most mature?

A
  • Pronormoblast
  • Basophilic Normoblast
  • PolychromaticNormoblast
  • OrthochromicNormoblast (Nucleated Red cells)
  • Reticulocyte
  • RBC
33
Q

Which of the RBC precursor cells is biggest and most immature, and has fine chromatin with evenly distributed strands?

Also what color is it?

A

Pronormoblast

Blue (Basophilic)

34
Q

Which RBC cell is this?

A

Pronormoblast

35
Q

A blue (basophilic) cytoplasm is due to the presence of what?

A

RNA

(A basophilic normoblast is deeply basophilic due to large amount of RNA)

36
Q

From pronormoblast to basophilic normoblast, what happens?

A

Cell gets smaller, nucleus gets smaller and chromatin is coarser. The strands are thicker and one may find clumps. Here is a pic!

37
Q

From basophilic normoblast to polychromatic normoblast, what is the key difference?

A

This stage is the first time that hemoglobin is visible!

There is still some residual RNA in cytoplasm which will cause it to stain a bluish-pink.

38
Q

From Polychromatic Normoblast to Orthochromic Normoblast, what is important to know?

A
  • This stage cannot undergo mitosis and is the last nucleated stage. The nucleus looks solid and doesnt have threads.
  • It is slightly larger than a mature RBC
39
Q

Seeing lots of these is bad! What are they?

A

Orthochromic Normoblast. Aka nucleated RBCs.

40
Q

Heres abother picture of a nucleated red blood cell (NRC):

A
41
Q

What happens from orthochromic normoblast to reticulocyte?

A

Nucleus gets ejected

*Here is a picture of reticulocytes in a sample of normal RBCs. Note how they are slightly more blue.

42
Q

What is the range of a normal reticulocyte count?

A

0.5 - 1.5%

43
Q

RBC maturation normally occurs in a synchronous fashion with changes in the cytoplasm and nucleus color, and overall cell size. Asynchrony in RBC morphology occurs when nuclear development lags behind that of the cytoplasm such as is seen in what conditions?

A

megaloblastic anemias: pernicious anemia and folic acid deficiency

44
Q

The…………………. is the single best criteria for identifying a cell, especially the cell’s age.

A

nuclear chromatin pattern

45
Q

The only RBC stages seen in a normal adult are the mature RBCs and the immediate precursors the reticulocyte. What is it called when you have lots of reticulocytes (RBCs with residual RNA)?

A

polychromasia

46
Q

As RBCs become mature, what color do they stain?

A

Pink

47
Q

What is the important neutrophil precursor we need to know?

A

Bands. (Cells in which the nucleus hasnt segmented yet)

48
Q

What does presence of bands indicate?

A

signals that the bone marrow is releasing more WBCs! This is usually due to an infection or inflammation.

49
Q

What do we need to know about this graph?

A

The last peak is neutrophils. When there is an increased number of bands, the peak shifts LEFT!

50
Q

What drug is used for stimulating neutrophil recovery following chemotherapy, and for peripheral stem cell donation?

A

Granulocyte-colony stimulating factor (G-CSF) filgrastim

MCM final (3 decks)

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