Metabolism 13

Question 1

The Liver Plays an Important Role in the Metabolism of Drugs and Xenobiotics.

For the kidney to eliminate drugs and xenobiotics, what form must these compounds be in?

Describe/draw Phase 1 and 2 in metabolism of drugs.

Answer 1

For the kidney to eliminate drugs, xenobiotics (foreign compounds) or their metabolites, these
compounds must be made hydrophilic. Although drugs & their metabolites are not always hydrophilic, there are two reactions (phase 1 and phase 2), which convert these compounds to a
hydrophilic form.

Phase 1 reactions involve the introduction of OH or COOH groups, usually through the oxidation of the parent compound. The necessary enzymes are present as an enzyme complex of NADPH-cytochrome P450 reductase [NADPH-cytochrome c P450 reductase & hemoproteins
(cytochrome P450)].

In Phase 2, the products of phase 1 reactions are conjugated with compounds (e.g. glucuronic acid, glycine, taurine, sulfate) to make them more hydrophilic.

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Question 2

Draw a picture of the liver’s role in carbohydrate metabolism.

Answer 2

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Question 3

Draw a picture of the liver’s role in metabolism of lipids.

Answer 3

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Question 4

The Liver Produces Most of the Circulating Plasma Proteins. It Also Produces Urea and Plays an Important Role in the Synthesis and Interconversion of Amino Acids.

Draw.

Answer 4

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Plasma proteins: 
albumin
fibrinogen
prothrombin
transferrin
haptoglobin
hemopexin
many more

Question 5

Fat Soluble Vitamins (A, D, & K) Are Stored in the Liver.

Draw metabolism of vitamin A (retinol) by the hepatocyte.

How is retinol transported?
What happens when blood levels of vitamin A decrease?

Answer 5

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Vitamin A: Retinol is transported in chylomicrons as an ester of long chain fatty acids. When blood levels of vitamin A decrease, the liver mobilizes the vitamin by hydrolyzing retinyl ester. The resulting retinol binds to retinol-binding protein, which is then secreted into the blood.

Question 6

Describe Vitamin D and K.

How is Vitamin D3 transported? Where are the major vitamin D stores located?
What is responsible for initial activation of vitamin D?

Where is the major store for vitamin K? Vitamin K is needed in the synthesis of what protein?

Answer 6

Vitamin D: Vitamin D3 is transported in chylomicrons in a nonesterified form. The major vitamin D stores are found in adipose tissue and skeletal muscle. Liver is responsible for the initial activation of D3; it converts this form to 25-hydroxycholecalciferol and it synthesizes the
vitamin D-binding protein.

Vitamin K: Although the major store of vitamin K is in skeletal muscle, its presence is required in the hepatocyte for the synthesis of prothrombin.

Question 7

Describe the liver’s storage and homeostasis of iron.

Describe the liver’s storage of copper.

Describe the liver’s modification or amplification of the following hormones:
D3-
Thyroid hormones-
IGF-

Answer 7

The liver is the major site of synthesis of several proteins involved in iron transport &
metabolism.

The liver stores copper (Slide # 25)
Sixty to eighty percent of the copper absorbed in the intestines is taken up into the
hepatocyte.
More than 80% of the copper absorbed each day is excreted in the bile.

The liver can modify or amplify hormone action (Slide # 26)
D3: conversion to 25-hydroxycholecalciferol
Thyroid hormones: conversion of T4 to T3
IGF: synthesis of IGF’s (somatomedins)

Synthesis of IGFs (another name for IGF is somatomedins), which is stimulated by somatotropin (STH). IGF is a growth promoting hormone

Question 8

How does iron affect ferritin and transferrin?

How is iron stored in liver?

Answer 8

Iron stimulates ferritin synthesis

Iron inhibits transferrin synthesis.

iron stored as ferritin in the liver. can be lysed through lysosomes and granulated and removed from liver.