Biochem: Iron Metabolism And Metabolic Interrelationships

Front 1

What is the normal quantity of transferrin that is saturated, half saturated, and free?

Back 1

In the normal physiological state ~ 1/9 transferrin is saturated, ~ 4/9 transferrin is half saturated, and ~4/9 transferrin is free.

Front 2

How is iron transported?

Back 2

Iron is transported in the blood by the glycoprotein transferrin. Transferrin tightly binds ferric iron but is also dependent on binding an anion (carbonate)

Front 3

Where is transferrin synthesized?

Back 3

in the liver as a single polypeptide with two noncooperative iron binding sites.

Front 4

How is iron internatilized into cells?

Back 4

Transferrin binds to the transferrin receptor on cell surfaces to deliver iron. The receptor-transferrin complex is internalized upon phosphorylation by Ca2+-calmodulin-protein kinas C complex. Iron is released from transferring when the pH decreases in the lysosomes

Front 5

Why is iron released from transferrin in the lysosomoes when the ph decreases?

Back 5

Transferrin only binds Fe3+(ferric) iron which exists at neutral or alkaline pH. Acidic pH converts iron to Fe2+(ferrous) which does not bind to transferrin.

Front 6

What happens to transferrin after iron is released in the lysosome?

Back 6

The receptor-apotransferrin returns to the cell surface and releases apotransferrin to be reutilized in the plasma.

Front 7

Why is free iron in the body dangerous?

Back 7

Many microorganisms require iron for replication and function.

An individual overloaded with iron may have free ferric iron in the blood serum.

Microorganisms that are usually nonpathogenic can become pathogenic when allowed access to free iron

Front 8

How can diabetes mellitus increase susceptibility for infections?

Back 8

Diabetes mellitus can sometimes trigger ketoacids which decrease the ability of transferrin to bind iron. The free iron increases the susceptibility of the patient to infection

Front 9

How does S. aureus acquire iron in the human body?

Back 9

secretes hemolysin which ruptures the membranes of a few erythrocytes. The released hemoglobin yeilds free heme that is captured and transported into the bacteria. Bacterial enzymes release the free iron and utilize it

Front 10

How is lactoferrin an antimicrobial?

Back 10

It is contained in human milk and protects new-borns from gastrointestinal infections by binding free iron

Front 11

How does E. coli aquire iron from lactoferrin?

Back 11

releases iron chelators which strip the iron from lactoferrin and transfer the iron to the microbe

Front 12

What is the major protein involved in iron storage?

Back 12

ferritin

Front 13

What is the maximum quantity of iron that ferritin can hold?

Back 13

4500 iron atoms, but usually has less than 3000

Front 14

Where does most iron storage occur?

Back 14

in hepatocytes, reticuloendothelial cells, and skeletal muscles

Front 15

What is the normal iron requirement for males?

Back 15

1mg/day

Front 16

What is the normal iron requirement for postmenopausal women? Premenopausal?

Back 16

Post = 1mg/day; pre= 4 to 5mg / day

Front 17

How is iron lost from the body?

Back 17

the normal sloughing of tissues that are not reutilized (epidermis and gastrointestinal mucosa)

Front 18

What is the major site of dietary iron absorption?

Back 18

small intestine with the largest amount being absorbed in the duodenum

Front 19

How is iron absorbed through a mucosal cell?

Back 19

Ferrous iron binds to divalent metal transporter 1 (DMT1).

Ferric iron binds to a transmembrane protein (Integrin) or is reduced by ferrireductase (R) and brought in as Fe2+.

Integrin transfers iron into the cytoplasm where mobilferrin (M) shuttles iron to ferritin for strorage.

DMT1 can deposit iron for storage to ferritin or shuttle iron over to a transmembrane protein, ferroportin 1.

Ferroportin 1 transports iron out of the mucosal epithelial cell.

The protein hephaestin oxidizes Fe2+ to Fe3+ so that trasferrin will bind the iron and carry it through the bloodstream.

Front 20

What regulates the transfer of iron across the mucosal-capillary interface?

Back 20

the synthesis of apoferritin. When little iron is required by the body, a large amount of apoferritin is synthesized to trap iron within the mucosal cell. This prevents iron from being transferred to the capillary. Mucosal cells slough off within a week and their contents are extruded into the intestinal lumen without being absorbed

Front 21

In the well-fed state, what supplies the energy requirements?

Back 21

the diet

Front 22

Why are amino acis used for protein synthesis before they are metabolized for other uses?

Back 22

The liver metabolizes aas, but the Km values of the enzymes involved are high.

This means that aas have to be at very high concentrations before significant catabolism can occur.

The tRNA-charging enzymes that form aminoacyl-tRNAs have low Km values for aas.

This ensures protein synthesis can occur as long as all the aas are present.

Front 23

What is the fate of dietary TAG in the well fed state?

Back 23

Dietary TAGs, packaged as chylomicron, travel through the bloodstream and bind to endothelial cells supplying muscle and adipose tissues.

Because of the high fat content of the human diet, most TAGs originate from the diet rather than de novo lipogenesis.

Front 24

What is the effect of dietary glucose on pancreatic beta cells and insulin?

Back 24

The b-cells of the pancreas are very responsive to the glc levels.

When glc enters the b-cell, glc oxidation raises the ATP level which closes ATP-sensitive potassium channels, depolarizes the cell, and increases intracellular calcium causing insulin to be released.

When glc increases, insulin increases.

Front 25

What is HbA1c?

Back 25

HbA1c is the product of glucose binding to the amino terminus of proteins. The aldehyde form of glc binds to the amine forming a schiff base which rearranges to form an amino ketone linkage

Front 26

What do HbA1c levels reflect?

Back 26

. HbA1C levels reflect the level of glc and the duration of the hyperglycemia. In prolonged hyperglycemia, HbA1C levels can rise to 12% or more of the total Hb.

Patients with diabetes have high glc and therefore high HbA1C levels. The changes in HbA1C can be used to follow the effectiveness of treatment for diabetes.

Front 27

What happens to insulin levels during early fasting state?

Back 27

decrease

Front 28

What maintains blood glucose in the early fasting state?

Back 28

hepatic glycogenolysis

Front 29

What happens to lactate, pyruvate and alanine during the early fasting state?

Back 29

Lactate, pyruvate, and alanine are diverted from oxidation and FA synthesis into glc formation.

Alanine returns to the liver for gluconeogenesis (the alanine cycle).

Lactate returns to the liver for gluconeogenesis (the cori cycle).

The liver has a 10 to 12 hour supply of glycogen.

Front 30

Where does energy come from in greater than 12 h fasting state?

Back 30

Fasting longer than 12 hours relys on hepatic gluconeogenesis.

Front 31

Why can FAs not be used for glucose synthesis in greater than 12 h fasting?

Back 31

FAs cannot be used for glucose synthesis because no pathway exists to convert acetyl CoA of FA oxidation into glc.

Front 32

How does the liver produce glucose for the brain in greater than 12 h fasting?

Back 32

The liver uses lactate, alanine, and glycerol to generate glc for peripheral tissues that can not generate glc for themselves (the brain).

Front 33

Where does most of the carbon come from for glucose synthesis during greater than 12 h fasting?

Back 33

Protein from skeletal muscle provides most of the carbon for glc synthesis.

Gln and Ala are released in the largest amounts.

Front 34

What happens to enterocytes and lymphocytes during greater than 12 h fasting?

Back 34

Enterocytes and lymphocytes are rapidly dividing cells which require energy.

Gln is used as an energy source by enterocytes with the end product being Ala.

Lymphocytes and macrophages use Gln for energy and produce Aspartate.

Front 35

How is Gln converted to Ala in enterocytes?

Back 35

Enterocytes convert Gln to Glu.

Glu is transamidated with pyruvate to form a-KG and Ala.

a-KG is converted to malate via the TCA cycle.

Malic enzyme generates pruvate used to form alanine.

Front 36

What happens to Gln in lympocytes and macrophages during greater than 12 h fasting?

Back 36

Gln is converted to Glu andglu is transamidated with OAA to form Asp and alpha KG

Front 37

What does FA oxidation provide in the liver?

Back 37

ATP for gluconeogenesis

Front 38

What does FA oxidation do in the heart and muscle?

Back 38

inhibits glycolysis and pyruvate oxidation

Front 39

What does the liver use to form ketones?

Back 39

acetyl Coa from FA oxidation (occurs in mt)

Front 40

What activates lipolysis in adipose tissue?

Back 40

low blood insulin to glucagon ratio

Front 41

Can FAs cross the blood-brain barrier?

Back 41

No, FAs cannot cross the blood-brain barrier and cannot be used as an energy source by the brain.

Front 42

What effect does ketone bodies have on catabolism of muscle tissue?

Back 42

`Ketone bodies reduce the need for glc thus reducing proteolysis of muscle tissue.