This ppt is about the variations in metabolic processes between different types of cells in different organs of our body. The reasons for the variations are also descried. This is the first set of slides on the topic.

1. Organ based metabolism-Liver
Dr. Radhakrishna G Pillai
Department of Life Sciences
University of Calicut

2. Liver
• The metabolic activities of the
liver are essential for;
– providing fuel to the brain,
muscle, and other peripheral organs
• The liver constitute 2% - 4% of body weight
• It is an organism's metabolic hub
• Most compounds absorbed by the intestine first pass
through the liver,
• thus Liver is able to regulate the level of many
metabolites in the blood

3. Liver
• The liver removes two-thirds of the glucose from the blood and all
of the remaining monosaccharides
– Remaining glucose is left in the blood for other tissues
• The absorbed glucose is converted into glucose 6-phosphate by
hexokinase and the liver-specific glucokinase
• The liver uses little of Glucose 6-phosphate to meet its own energy
needs
• Much of the glucose 6-phosphate is converted into glycogen
• As much as 400 kcal (1700 kJ) can be stored in this form in the liver
• Excess glucose 6-phosphate is metabolized to acetyl CoA, which is
used to form fatty acids, cholesterol, and bile salts

4. Pentose phosphate pathway
• The pentose phosphate pathway;
– another means of processing glucose 6-phosphate
– supplies the NADPH for these reductive biosynthesis
• The liver can produce glucose for release into the
blood by breaking down its store of glycogen and by
carrying out gluconeogenesis
• The main precursors for gluconeogenesis are;
– lactate and alanine from muscle
– glycerol from adipose tissue and
– glucogenic amino acids from the diet

5. Liver- lipid metabolism
• The liver also plays a central role in the regulation of lipid
metabolism
• When fuels are abundant;
– fatty acids derived from the diet or synthesized by the liver are
esterified and
– secreted into the blood in the form of very low density lipoprotein
• In the fasting state, the liver converts fatty acids into ketone
bodies
• The fate of fatty acids is made according to whether the fatty
acids enter the mitochondrial matrix
• Long-chain fatty acids traverse the inner mitochondrial
membrane only if they are esterified to carnitine

6. Liver
• Carnitine plays an essential role in energy metabolism
• It is either synthesized by the body or assumed from
diet containing meat and dairy products
• Acylcarnitines play an essential role in regulating the
balance of intracellular sugar and lipid metabolism
• They serve as carriers to transport activated long-
chain fatty acids into mitochondria for β-oxidation
• This is a major source of energy for cell activities
• The liver is the most important organ for endogenous
carnitine synthesis and metabolism

7. • The main function of carnitine is the transfer of long-chain
fatty acids to mitochondria for subsequent β-oxidation
• The mitochondrial membrane is impermeable to acyl-
CoAs and fatty acids must be conjugated to carnitine to
enter mitochondria
• Carnitine forms a high-energy ester bond with long chain
fatty acids by the action of carnitine palmitoyl transferase
1 (CPT-1)
• Forms acylcarnitines
• CPT1 is located on the inner side of outer MC membrane

8. Acylcarnitine metabolism

9. Liver
• Carnitine acyltransferase I is inhibited by malonyl CoA
• When malonyl CoA is abundant;
– long-chain fatty acids are prevented from entering the
mitochondrial matrix
– the compartment of β-oxidation and ketone-body formation
• Instead, fatty acids are exported to adipose tissue for
incorporation into triacylglycerols
• The level of malonyl CoA is lower in fuel scarcity
• Under these conditions, fatty acids liberated from adipose
tissues enter the mitochondrial matrix for conversion into
ketone bodies

10. Acylcarnitines
• Acylcarnitines are then translocated across the inner
mitochondrial membrane by the carnitine acylcarnitine
translocase
• Once inside mitochondria, carnitine palmitoyl transferase 2 (CPT-
2), located in the inner mitochondrial membrane, removes
carnitine from acylcarnitines and re-generates acyl-CoAs
• Carnitine then returns to the cytoplasm for another cycle (using
CACT)
• While the acyl-CoAs can enter (in aerobic conditions and in the
presence of low levels of ATP) β-oxidation with
• final production of acetyl-CoA for oxidative phosphorylation or
production of ketone bodies in the liver

12. Liver – amino acid metabolism
• The liver also plays an essential role in dietary amino acid
metabolism
• The liver absorbs the majority of amino acids, leaving some in
the blood for peripheral tissues
• The priority use of amino acids is for protein synthesis rather
than catabolism
• How are amino acids directed to protein synthesis in
preference to use as a fuel?
– The KM value for the aminoacyl- tRNA synthetase is lower than that
of the enzymes taking part in amino acid catabolism
– Thus, amino acids are used to synthesize aminoacyl-tRNAs before
they are catabolized

13. Amino acid catabolism
• The first step is the removal of nitrogen, which is subsequently processed
to urea
• The liver secretes 20 to 30g of urea a day
• The α-keto acids are then used for gluconeogenesis or fatty acid synthesis
• The liver cannot remove nitrogen from the branch-chain amino acids
(leucine, isoleucine, and valine)
• Branch chain amino acid transamination takes place in the muscle

14. Liver – energy release
• α-Ketoacids derived from the degradation of amino
acids are the liver's own fuel
• The main role of glycolysis in the liver is to form
building blocks for biosynthesis
• Liver has little of the transferase needed for activating
acetoacetate to acetyl CoA
• So the liver cannot use acetoacetate as a fuel
• Thus, the liver avoids the fuels that it exports to
muscle and the brain

15. Organ based metabolism
• Metabolic process in each organ is unique
• It symbolises the physiological role of each organ in our body
• The enzymes needed for this varying metabolic pathways are
present in each organ
• There are different levels of similarity in metabolism between
organs depending on their functional resemblances
• This variations in metabolism between organs are key to the
homeostasis in body

16. Thank You
Radhakrishna G Pillai
Pillai_radhakrishna@hotmail.com
0091 9495554891