Download Liver Function - Wk 1-2

Liver Function
1. Outline the processes of heme catabolism including the formation
of bilirubin, its uptake and conjugation in the liver, excretion in the
bile and formation of other pigments in the gut
The lifespan of a Red Blood Cell (RBC) is roughly 120 days. After this time, the heme is degraded
and its catabolites are processed for excretion. The process is as follows;
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Macrophages of the reticuloendothelial cells, principally in the spleen (but also in the BM and
liver), ingest the dead, dying or damaged RBC. Firstly, the Globin and the Iron (Fe) of the
Haemoglobin molecule are removed and recycled.
The heme is then converted to Biliverdin via enzyme Haem oxygenase
Biliverdin is converted to Bilirubin via Biliverdin reductase
At this point, Bilirubin is insoluble in water and is considered “Unconjugated Bilirubin”
It is then released into the bloodstream and travels to the liver bound to the plasma protein
Albumin
When it reaches the liver it enters the hepatocytes where it detaches from albumin. It cannot
enter the bile at this point as it is insoluble in water. It is therefore conjugated (added to) with
compounds in order to make it water soluble (ie glucuronic acid, sulphates)
This is the form of Bilirubin considered “Conjugated Bilirubin”, its water solubility allowing
it to pass into bile canaliculi, which can then be secreted into the duodenum along with Bile.
Inside the Small Intestine, bacteria metabolise conjugated bilirubin, deconjugating it to
urobilinogen
The urobilinogen can be reabsorbed in the ileum (20%) and transported back to the liver via
the portal system, where it can be released again in bile, or transported to the kidneys,
urobilinogen oxidised to urobilin (yellow) on exposure to air and excreted in the urine.
Urobilinogen not reabsorbed from the Small Intestine pass into the colon and the microflora
there convert it to stercobilinogen. on exposure to air, stercobilinogen oxidized to stercobilin,
which is a dark red-brown pigment that provides the major colour of the stool
2. Describe the role of the liver in the regulation of blood glucose
concentrations, including synthesis of glycogen and fatty acids from
glucose, and the processes of glycogenolysis and gluconeogenesis
In order for cells to function normally, their blood glucose levels need to be kept
relatively constant (4-5 mmol). The pancreas plays a minor role in regulating blood
sugar levels via the production of the hormones Insulin and Glucagon. Insulin is an
anabolic hormone that promotes the storage and usage of glucose (get rid of it),
whereas glucagon mobilises glucose reserves (aims to produce glucose).
Post-Prandially, blood glucose levels rise. The liver acts to counter this and lower
levels by;
- Glycogenesis and Glycogen Storage – formation of Glycogen from glucose
- Oxidation of glucose – provide energy
- Excess glucose in the blood is converted to Triglycerides and fatty acids via
lipogenesis and stored as fat or adipose tissue
When glucose levels are low, the liver acts to raise levels via;
- Glycogenolysis – breakdown of glycogen to produce glucose
- Gluconeogenesis - The formation of glucose from non-carbohydrate sources,
such as glycerol, lactate, and a variety of amino acids
3. Indicate the role of the liver in the synthesis and breakdown of the
plasma proteins and the synthesis of urea.
Like all other biological molecules, proteins have a limited life span and must be
broken down and replaced before they begin to deteriorate. As proteins are broken
down, their amino acids are recycled and used in building new proteins or modified to
form a different N-containing compound. Newly ingested amino acids, as well as
derivatives from the Krebs Cycle are taken up by the cells of the liver via active
transport processes and used to replace and/or synthesise new proteins. These include
albumin, prothrombin, acute phase proteins, clotting factors, transport proteins etc.
When more protein is available than is needed for these anabolic purposes, amino
acids are oxidized for energy or converted to fat for future energy needs.
Before amino acids can be oxidized for energy, they must be deaminated, that is, their
amine group (NH2) must be removed. The resulting molecule is then converted to
pyruvic acid or to one of the keto acid intermediates in the Krebs cycle (i.e. acetyl
CoA, alpha (α) ketoglutaric acid, succinyl CoA, fumaric acid, or oxaloacetic acid).
The key molecule in these conversions is the nonessential amino acid glutamic acid.
The events that occur are as follows;
1. Transamination - A number of amino acids can transfer their amine group to αketoglutaric acid (a Krebs cycle keto acid), thereby transforming α-ketoglutaric acid
to glutamic acid. In the process, the original amino acid becomes a keto acid (that is,
it has an oxygen atom where the amine group formerly was). This reaction is fully
reversible.
2. Oxidative deamination - In the liver, the amine group of glutamic acid is
removed as ammonia (NH3), and α-ketoglutaric acid is regenerated. The liberated
NH3 molecules are combined with CO2, yielding urea and water. The urea is released
to the blood and removed from the body in urine. Because ammonia is toxic to body
cells, the ease with which glutamic acid funnels amine groups into the urea cycle is
extremely important. This mechanism rids the body not only of NH3 produced during
oxidative deamination, but also of blood borne NH3 produced by intestinal bacteria.
3. Keto acid modification - The goal of amino acid degradation is to produce
molecules that can be either oxidized in the Krebs cycle or converted to glucose.
Hence, keto acids resulting from transamination are altered as necessary to produce
metabolites that can enter the Krebs cycle. The most important of these metabolites
are pyruvic acid, acetyl CoA, α-ketoglutaric acid, and oxaloacetic acid (Figure 24.7).
Because the reactions of glycolysis are reversible, deaminated amino acids that are
converted to pyruvic acid can be reconverted to glucose and contribute to
gluconeogenesis.
4. Recognize that the liver generally utilizes fatty acids for its own
energy requirements.
The liver generally uses fatty acids for its own metabolic requirements because they
give a higher energy yield than glucose. The liver also saves its glucose stores for
times of fasting so that it can supply the brain during times of need. The liver utilises
glucose only during times of plenty, such as after a meal.