Lecture 6.5 Biochemistry

Question 1

Describe the following graph

Answer 1

Embryonic hemoglobin has zeta, alpha, episilon, and gamma

Adult hemoglobin has alpha, beta, and delta

The alpha from the embryo stays and the epsilon and gamma go away

Question 2

Describe what is happening in the picture

Answer 2

Oxygen binds to the iron and it moves in plane with the porphyrin

Pulls down the proximal histidine and changes the interaction associated with the globin chain

Question 3

Describe what is happening in this graph

Answer 3

Shows the saturation of O2 for myglobin and hemoglobin

Hyperbolic curve for myoglobin: oxygen becomes very saturated very quickly

Sigmoidal curve for the hemoglobin; because globin subunits

Cooperativity

Binding to O2 is REVERSIBLE

Question 4

What is the affect of a lowered pH on the binding affinity for O2 and hemoglobin?

Answer 4

The Histidine picks up an H+ from the tissue and this favors the release of the oxygen from the Hb

**actively respiring tissues have a low pH because you want the O2 to be released

Question 5

Describe positive cooperativity of the Hb

Answer 5

The binding of one oxygen lowers the F8 histidine down and the other globin chains down so that the O2 is able to bind to the Hb molecule on another subunit

Question 6

What is the affect of 2,3-BPG on the Hb?

Answer 6

Shifts the OD to the right and reduces the affinity of O2 to the Hb

Hb releases the O2 to the tissues

Question 7

Describe sickle cell anemia

Answer 7

There is a deletion that causes a valine substitution for a glutamate at the 6th position

polymerization of the heme which causes the sickled shape

The RBC causes blockage of the vessels because they are not able to fit or fold into the capillaries

Question 8

Describe the absorption and storage of heme iron

Answer 8

Heme iron is from animal products and is absorbed as Fe2+

Enters the enterocyte and is oxidized to Fe3+ via ferroxidase

Stored as ferritin in the liver

Question 9

Describe the absorption and storage of non-heme iron

Answer 9

Fe3+

From plant products

Fe3+ is converted to Fe2+ via ferric reductase

Fe2+ enters the enterocyte via DMT1

Converted back into Fe3+ by ferroxidase

Exported out by ferroportin (hephastin required and regulated by hepcidin)

Trasnferrin takes the Fe3+ to the transferrin receptor which is then endocytosed and regulates the iron homeostasis

Question 10

What happens when iron is low in regards to hepcidin, ferroportin, and iron absoprtion?

Answer 10

Hepcidin is down (expression)

Ferroportin is up

Iron absorption is high

Question 11

List some of the causes of an iron deficiency

Answer 11

Insufficient iron in diet

Not enough absorption

Blood loss via menstruation

Overuse of aspirin

Ulcers in GI

HYPCHROMIC MICROCYTIC ANEMIA

Treatment

Dietary iron supplementation

Question 12

List some of the causes of an iron overload

Answer 12

Hereditary hemochromatosis

Increased absorption of iron

Heart, liver, and pancreas

Autosomal recessive

HFE gene

C282Y homozygotes

Dysregulation of iron uptake and export by enterocyte

Total body

Normal: 3-5 g

HH: 15 g

Question 13

What is folate used to help make? What is the function or benefit of this compound?

Answer 13

THF

Serves as an imp for purine and pyrimidine synthesis

DNA synthesis!!!

Question 14

What happens if there is a folic acid deficiency?

Answer 14

Decreased DNA synthesis which can lead to megaloblastic macrocytic anemia

Question 15

What will happen to vitamin B9 if vitamin B12 is not present?

Answer 15

NEEDS vitamin B12 or it will be stuck in N5-mrthyl-THF

Question 16

Describe the schilling test. What is the purpose of this test?

Answer 16

To see if the B12 deficiency is dietary or an absorption issue

Patient gets an oral dose of 57Co labeled B12 and a 24 hour urine is done

If there is B12 in the urine, then it is a dietary issue

If it is not, repeat WITH an intrinsic factor and if the B12 is present in the urine after this then it was an absortion issue