Liver protein and glucose metabolism and bile

Question 1

What is protein turnover? When is an increase seen? In starvation, amino acids from degraded skeletal muscle are used in what process?

Answer 1

The continuous degradation and re-synthesis of all cellular proteins.
When tissues are undergoing structural re-arrangement e.g. damage due to trauma, uterine tissue during pregnancy, in skeletal muscle during starvation
Gluconeogenesis

Question 2

Second reason for increased protein turnover? 2 primary methods of protein breakdown?

Answer 2

Due to severe burns- significant protein amounts can be lost in exudate from damaged tissue
Lysosomal and ubiquitin- proteasome pathway

Question 3

Where is lysosomal protein breakdown carried out in? Comprised of what 3 cell types? Sinusoidal cells remove soluble proteins from blood through what? Remove what protein types? Once in liver, fused into what structures?

Answer 3

Reticula-Endothelial system of the liver
Sinusoidal endothelial cells, Kupffer cells and pit cells
Fenestrations known as sieve plates on luminal surface
Fibrin, fibrin degradation products, collagen and IgG complexes
Lysosomes- lysozyme break protein down into AAs

Question 4

Kupffer cells package proteins into what structures?

Answer 4

Phagosomes- contain hydrolytic enzymes

Question 5

Where does ubiquitin- proteasome pathway of protein breakdown occur? Degradation is what process type? What does rate of protein degradation depend on?

Answer 5

In cytoplasm of cells
Selective
Structure of protein- denatured protein= more readily digested than with intact conformation

Question 6

How can proteins be targeted for degradation? This directs the protein to where?

Answer 6

By the attachment of a small peptide called ubiquitin

Protein complex called a ‘proteasome’

Question 7

Amino acid catabolism requires what to be removed? Produces what 2 products?

Answer 7

The alpha amino group to be removed

Nitrogen- incorporated into other compounds/ excreted and carbon skeleton- metabolised in Krebs cycle

Question 8

2 main catabolism processes in amino acid breakdown? Oxidative deamination results in liberation of an amino group as what? Only amino acid to undergo rapid oxidative deamination?

Answer 8

Oxidative deamination and transamination
Free ammonia (NH3)
Glutamate

Question 9

During oxidative deamination, what is produced other than NH3 (using water)? The alpha-keto acid can be used after in what process?

Answer 9

Oxygen from water is used to form a alpha-keto acid

Krebs cycle to produce glucose= gluconeogenesis (reversing Kreb’s and glycolysis to start)

Question 10

Coenzyme used in oxidative deamination? Enzyme used too? The NH3 produced can be used to produce what?

Answer 10

NAD+
Glutamate dehydrogenase (when metabolising glutamate)
Urea via urea cycle- very toxic

Question 11

What process is oxidative deamination? If there is an excess of NH3, what can happen? Reacts with what to decrease the amount of ATP?

Answer 11

Reversible
NH3+ can easily cross the BBB
Alpha-ketoglutarate

Question 12

What does transamination involved? If the amino acid is alanine, the amino group is transferred to the keto-acid to form what? Uses of products?

Answer 12

The transfer of an alpha-amino group from an amino acid to a ketone-acid to form an alpha-keto-acid
To alpha-ketoglutarate to form pyruvate (used in Krebs) and glutamate (can be oxidatively deaminated)

Question 13

Enzyme involved in transamination? This is found where? Mostly in what organs? If alanine being transaminated, what enzyme is used? How can transamination and oxidative deamination work together?

Answer 13

Aminotransferase
In cytosol of mitochondria- particularly in kidneys and liver
Alanine aminotransferase (ALT)
The alpha-keto-acid formed from oxidative deamination can be used along with an AA in transamination to form another AA and so on

Question 14

What is the nitrogen balance? What reaction has a positive nitrogen balance? What reaction has a negative nitrogen balance? People are what if balance is in equilibrium?

Answer 14

A measure of equilibrium of protein turnover
Anabolic- net gain in AAs
Catabolic- net loss in AAs
Healthy

Question 15

What is an essential amino acid? How many are there? What happens if any of them are missing from out diet?

Answer 15

Those the body cannot synthesise
9
A negative nitrogen balance results

Question 16

Most common cause of positive nitrogen balance? Recommended daily intake of AAs compared to normal man/ woman? Intake in first few months of life? Most common cause of negative nitrogen balance?

Answer 16

Pregnancy- 1.3g/kg compared to 0.8g/kg
2.4g/kg bodyweight
Malnutrition, multiple or extensive trauma

Question 17

In muscles, aminotransferases e.g. ALT, can use pyruvate as a what for transamination? This produces what products? Alpha-ketoglutarate formed can be used in what cycle?

Answer 17

An alpha-keto acid

Alanine and alpha-ketoglutarate- used in Krebs cycle to produce glucose via gluconeogenesis

Question 18

Excess alanine from glucose-alanine cycle goes where? The alanine is converted back to what? Glucose then used how? Glutamate produced used how?

Answer 18

Into the bloodstream and into the liver
Back to pyruvate by transamination– gluconeogenesis
Used to make pyruvate in muscles by glycolysis– removes excess NH3
Converted into NH4+ via oxidative deamination– NH3– urea via urea cycle

Question 19

All enzymes used in urea cycle found where? Starting amino acid of urea cycle? Cleaved by what forming what 2 products? What 2 things are built on to ornithine to form citruline? Another molecule of what is added to regenerate arginine?

Answer 19

In liver in either mitochondria/ cytosol of hepatocytes 
Arginine from diet/ protein breakdown 
Arginase-- urea and ornithine 
NH3 and CO2 
NH3

Question 20

The reactions of one urea cycle turn consume how many ATP and high energy nucleotides? Deficiencies of any enzymes involved in cycle results in what?

Answer 20

3 ATP and 4 high energy nucleotides (PO4-)

Higher levels of ammonia in blood and incompatible with life.

Question 21

Why is ammonia neurotoxic?

Answer 21

Crosses BBB– converted to glutamate using glutamate dehydrogenase– less alpha-ketoglutarate– less oxaloacetate– halting Krebs cycle– cell damage and neural cell death

Question 22

What happens during absorptive state? During the absorptive state, what is glucose used for? 2 other things?

Answer 22

Nutrients absorbed from GI tract and some are catabolised and used/ stored for future use
To generate ATP and to make glycerol
Amino acids– proteins, glycerol and fatty acids– lipids

Question 23

What happens during the post-absorptive state? What must supply the body’s energy requirements? In the post-absorptive state, what are the 3 main sources of glucose?

Answer 23

Nutrients aren’t absorbed from the GI tract
Nutrient stores
Glycogenlysis, lipolysis and proteins

Question 24

What is glycogen hydrolysed to in the liver? Then what happens? Hepatic glycogenolysis begun how? Can supply body for how long?

Answer 24

Glucose-6 phosphate
Enzymatically converted to glucose which enters the blood
Within seconds due to sympathetic nervous system stimulation- first line of defence in homeostatic plasma glucose control
Several hours until stores nearly depleted

Question 25

Why is muscle glycogen not a source of blood glucose? Instead what does glucose-6 phosphate undergo? Some lactate goes where?

Answer 25

Does not have enzyme to form glucose from glucose-6 phosphate
Glycolysis to make ATP, pyruvate and lactate
Into blood and to liver to make glucose which can leave liver cells into blood

Question 26

How are triglycerides used to form glucose? When does protein become source of blood glucose in post-absorptive state? Amino acids from proteins used how? How many ATP molecules consumed per molecule of glucose formed?

Answer 26

Glycerol enters liver and is converted through series of steps into glucose
Few hours- continued protein loss– death
In liver via alpha-keto acid pathway to form glucose
6

Question 27

How often is bile secreted from the liver? Used for what? Stored where? Where is this located?

Answer 27

More or less continuously
Emulsifies fats and excretory pathway for most steroid hormones, many drugs and some toxins metabolised by the liver
In gall bladder- junction of right mid-clavicular line and costal margin

Question 28

What is the functional unit of the liver? Formed of what stacked on top of each other? Are what shape with what in each corner? What does portal triad consist of?

Answer 28

Hepatic lobules
Hepatic plates
Hexagonal with a portal triad at each corner
Hepatic portal vein, hepatic artery and a bile duct

Question 29

What runs up the centre of a hepatic lobule? Substances absorbed from the SI wind up where? What is found here?

Answer 29

The central vein which eventually becomes the hepatic vein
In the hepatic sinusoid- blood vessel with fenestrated discontinuous endothelium
Oxygen-rich blood from the hepatic artery and nutrient rich blood from the portal vein

Question 30

Hepatocytes are separated from the sinusoids by what? Reaches either of what 2 things?

Answer 30

The space of disse

Vena cava via the central vein/ taken up by hepatocytes where can be modified

Question 31

Hepatic lobules are what shape and how deep? % of blood supply from portal vein? From hepatic artery? Where does the formed bile travel in relation to he blood?

Answer 31

Wedge-like arrangements around 1-2 cells deep
80% and 20%
In the opposite direction

Question 32

What are the sinusoids line with? What’s on the undersurface of the sinusoids? Responsible for what?

Answer 32

Specialised endothelial cells interspersed with Kupffer cells
Stellate cells- produce extracellular matrix in the space of disse

Question 33

What is between adjacent hepatocytes? What are they and what are they bound by? What filaments are found in areas around the canaliculi? What do they serve to do?

Answer 33

Bile canaliculi- like a groove bound by tight junctions, gap junctions and desmosomes which cross both cell membranes
Actin filaments- serve to pump the formed bile towards the bile ducts

Question 34

Where do the bile ducts in the hepatic lobules draw into? What duct joins the common hepatic duct- forms what?

Answer 34

The left/ right hepatic ducts– join into common hepatic duct
Cystic duct– common bile duct

Question 35

The pancreatic duct joins the common bile duct at what point? These two ducts enter the duodenum at what point? What is sphincter around these 2 ducts called?

Answer 35

The ampulla of Vater
Major duodenal papilla (2nd part)
Sphincter of Oddi

Question 36

6 major ingredients of bile?

Answer 36

Bile salts, lecithin(phospholipid,) HCO3-, cholesterol, bile pigments and trace metals

Question 37

What are bile salts, cholesterol and lecithin aggregated into? Why is this?

Answer 37

Mixed micelles- maintain aggregation in gall bladder even when concentrated
Bile salts= powerful detergents as are anionic and are separated because can damage cell membranes

Question 38

Components of bile are secreted by what 2 different cell types? Secretion of HCO3- by bile ducts stimulated by what due to presence of acid?

Answer 38

Hepatocytes; bile salts, cholesterol, lecithin and bile pigments
Epithelial cells lining bile ducts- most of HCO3- rich solution
Secretin

Question 39

Gallbladder receives bile from where? Hepatic bile enters gallbladder via what? Contracts under action of what? Due to what in duodenum?

Answer 39

Common hepatic duct- formed from left and right hepatic ducts
Cystic duct- stored and concentrated here
Cholecystokin(CCK)- amino and fatty acids

Question 40

Why is the vasculature of the gallbladder strange?

Answer 40

The cystic artery supplies oxygenated blood but has no venous drainage- drains directly into liver

Question 41

During digestion of a fatty meal, most bile salts entering intestine are absorbed by what? The absorbed bile salts are via what to where? Uptake into hepatocytes driven by what? Recyling pathway known as what?

Answer 41

Specific Na+-coupled transporters in the jejunum and terminal ileum
Portal vein to liver- again secreted into bile
Secondary active transport couple to Na+
Enterohepatic circulation

Question 42

% of bile salts ending up in faeces? How many times is bile salt content of body recycled during meal digestion? Via what circulation?

Answer 42

5%
Several times
Enterohepatic circulation

Question 43

Bile is synthesised from what substance? Liver also secretes this into where? How is cholesterol soluble in bile?

Answer 43

Cholesterol
Secretes cholesterol extracted from blood into the bile
Incorporated in micelles/ lipoproteins in blood

Question 44

Ring of muscle surrounding common bile duct at Ampulla of Vater? When this is closed, what happens?

Answer 44

Sphincter of Oddi- dilute bile from the liver is shunted into the gallbladder and is concentrated as some of the NaCL and water is absorbed into the blood.

Question 45

The bile duct system is a what system? When the gallbladder fills, the bile must exhibit what? What hormone is released after fatty meal due to fat in duodenum? This causes what?

Answer 45

Low pressure system.
Adaptive relaxation- the size increases but the pressure doesn’t
Cholecystokinin (CCK)
Sphincter to relax and gallbladder to contract- bile flows down cystic duct through common bile duct into duodenum