Inorganic nutrients II

Question 1

Copper absorption (intestine, Atp7a) characteristics?

Answer 1

Dietary Cu2+ must be reduced to Cu1+ by metalloreductase, before being absorbed by Ctr1

Once in the cell, it is carried by atox1 to the Atp7a transporter.

The Atp7a transporter also pumps the Cu1+ into the portal vein, where it is bound to albumin and transported

Question 2

Copper absorption (liver, Atp7b) characteristics?

Answer 2

Cu1+ (albumin complex) goes into the liver cell (Ctr1) and binds to ceruloplasmin after entering through Atp7b

The ceruloplasmin carries the Cu1+ into the plasma

Question 3

Copper deficiency overview?

Answer 3

Metallothionein binds dietary copper and traps it in the enterocyte (preventing normal absorption)

Question 4

Menke’s Dx (copper)

Answer 4

Caused by deficiency of the pump, Atp7a (intestine)

Inability to absorb dietary copper produces congenital copper deficiency

Sx: hypotonia, “pili torti” hair fibers

Question 5

Wilson’s Dx (copper)

Answer 5

Caused by deficiency of the pump, Atp7b (liver)

Inability to produce copper leads to decreased production of ceruloplasmin

Inability to excrete copper leads to eoxic accumulation in the liver

Sx: Liver cirrhosis/failure, copper deposits in iris

Question 6

Iron absorption characteristics?

Answer 6

Mainly protein-bound

Vitamin C reduces Fe3+ to Fe2+, the form in which it is absorbed

Fe2+ enters enterocyte via the divalent metal transporter 1 (DMT1)

Heme is internalized via clathrin

Question 7

Iron storage and transport

Answer 7

High iron lvls -> Fe2+ is oxidized to Fe3+ by ferritin, which stores the iron for later release

Ferroportin transports Fe2+ across the basolateral membrane

Hephaestin oxidizes Fe2+ to Fe3+

Fe3+ is then transported throughout the blood by transferrin

Question 8

Why is iron absorption and transport dependent on copper?

Answer 8

Ceruloplasmin is a ferroxidase that maintains transferrin iron in the Fe3+ state

Question 9

Iron deficiency anemia (IDA)

Answer 9

Caused by inadequate iron intake or excessive iron loss

CBC gives low total hemoglobin but normal RBC count

Decreased serum ferritin is diagnostic of IDA

Hypochromic (without color) RBCs are seen, histologically

Question 10

Hemochromatosis

Answer 10

HFE is normally receptor bound; in a mutation, HFE is free and binds to transferrin, which upregulates iron uptake

Sx: liver cirrhosis and failure, bronze skin (hemosiderin)