Case 5 Flashcards

1
Q

Describe what happens in the absorptive state?

A
  • Glucose is absorbed by the liver via GLUT2 receptors
  • When glucose is abundant glucokinase works to change glucose into glucose 6 - phosphate
  • High levels of glucose-6 - phosphate promotes glycogenesis forming of glycogen
  • High levels of glucose-6-phosphate promote production of NADPH in the PPP
  • Glucose-6-phosphate is used for glycolysis which is promoted by a high insulin/glucagon ratio
  • Surplus carbohydrates from a meal are converted to acetyl-CoA and then channelled into fatty acid synthesis
  • high ATP inhibits isocitrate dehydrogenase, leading to an accumulation of critrate in mitochondriart and export to the cytoplasm
  • ATP-citrate lyase restores acetyl-CoA in the cytoplasm and ACC is activated by dephosphorylation and by citrate
  • TAG synthesis is promoted by high availability of fatty acyl-CoA both from de novo fatty acid biosynthesis and from dietary fats
  • Surplus amino acis are recycled, redistribtued or degraded into pyruvate, TCA cycle intermediates or acetyl coA
  • Branched - chain amino acids are only used by muscle
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the end products of glycolysis

  • Under aerobic conditions
  • under anaerobic conditions
A
  • Aerobic conditions - pyruvate
  • Anaerobic conditions - lactate e.g. in muscles
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the functions of the following receptors:

GLUT2

GLUT4

A
  • GLUT2 - liver
  • GLUT4 - adipose tissue
  • Facilitate diffusion of glucose into cells, they are on the cell membrane
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

When glucose is taken up by the liver it is phosphorylated, descrie this process and name all the enzymes involved.

A
  • Glucose is phosphorylated by an ATP molecule to form glucose-6-phosphate
  • glucose-6-phosphate is trapped within the cell because it cannot cross the membrane spontaneously
  • this reaction is catalysed by a hexokinase enzyme specifically hexokinase IV/glucokinase which has a higher capacity to trap glucose in the liver but only when glucose concentrations are high after a meal
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the pyruvate dehydrogenase complex?

A

Pyruvate is shuttled into mitcochondria with the help of a dedicated transporter

  • The PDH complex is a group of enzymes copies of three enzymes E1,E2,E3
  • The PDH is inactivated by PDH kinase which is activated by high ATP/ADP and high NADH/NAD+ but inactivated by pyruvate
  • The complex needs no fewer than 5 cofactors some derived from vitamins
    • Thiamine - PP (B1)
    • Lipoic acid
    • Co-enzymes A from pantothenate B5
    • FAD from riboflavin B2
    • NAD from nicotinamide B3
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the TCA cycle

A
  • Central metabolite roundabout with multiple entry points, several of the intermediates are involved in gluconeogenesis, amino acid and heme metabolism
  • The oxidative catabolism of carbohydrates, lipids and amino acids came togethere here
  • All TCA cycle reactions happen in mitochondria and require oxygen to recycle to the reduced co-enzymes NADH + H+ and FADH2
  • Provides full oxidation of acetyl- CoA to 2CO2
  • Generates reducing agents which in the ETC generate 29 ATP per glucose molecule from PDH 22 from cycle and 2 GTP
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are excess carbohydrates or proteins in excess of the body’s needs converted to

A
  • Converted to fatty acids by the liver
  • Stored as fats (triacyglycerol in adipocytes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Explain the process of using acetyl CoA to make Fatty acids

A
  • Acetly-CoA is made in the mitochondria and cannot cross the membrane a shuttle is needed
  • It cannot be used to make glucose it can be used to make fatty acids in the cytoplasm or go through the TCA cycle to produce energy
  • ACC is used in the well fed state to make fatty acids, chain elongated from 2C to 16C
  • Insulin regulates promotes making of fatty acids, regulates transcription of this enzyme
  • Fatty acetyl CoA is the end product and leads to feedback inhibition stopping the first step of the cycle when made
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Regarding the beta oxidation (catabolism of fatty acids) how much ATP, FADH2, NADH, Acetyl-CoA are produced per 2 carbon molecule.

A
  • FADH2
    • ​2 ATP
  • NADH
    • 3 ATP
  • Acetyl CoA
    • 12 ATP
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is ketoacidosis

A
  • Overproduction of ketone bodies acidifying the blood
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What does the body use for an emergency fuel

A
  • Ketone bodies
  • Produced by the liber to preserve glucose, the liver itself cannot use ketone bodies, it releases them into the blood for peripheral tissues
  • During starvation the ability of the liver to oxidise fatty acids released from adipocytes may be limited
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What happens to excess amino acids

A
  • Excess amino acids are degraded and generated nitrogen is excreted as urea
  • in peripheral tissues excess ammonia is converted to glutamaine and shuttled to the liver
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Explain amino acid metabolism

A
  • Most amino acids can be used in gluconeogenesis (glucogenic) but some are partially or fully ketogenic - they can form acetyl-CoA or acetoacetate
  • Amino group is turned into a ketone group turning the molecule into an alpha-ketoacid which can be used in the TCA cycle, the breakdown of amino acids can be used in gluconeogenesis
  • The amino group is transfered to an alpha ketoglutarate in a transmaninase reaction
  • glutamate is a carrier of amine groups
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Which transmaninase enzyme is more indicative of liver damage and why?

A
  • ALT is more indicative of liver damage but serum AST is more sensitive because the liver contians larger amounts of AST than ALT
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How does ALT work?

A
  • Alanine transaminase
  • Turns alanine into an alpha ketoacid which is used for TCA
  • Removes the Alpha amine group from alanine and transfers it to glutamate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How does AST work?

A
  • Aspartate transaminase
  • Removes the Amine group from glutamate and gives it to oxaloacetate to form aspartate
  • Aspartae feeds into the urea cycle
17
Q

How is ammonia delivered to the liver via the alanine - glucose shuttle

A
  • Alanine from the muscle delivers NH3 via ALT
  • Resulting pyruvate goes into gluconeogenesis
  • Glucose is returned to the muscle
18
Q

What are the functions of the liver

A
  • Phagocytosis - of particles by Kupffer clles
  • Degradation of endogenous compounds and xenobiotics (drugs and toxins)
  • Activation and excretion of hormones
  • Excretion of lipophilic waste products - bile products
  • Secretion of emulsifiers - bile products
  • Storage of carbohydrates, lipids, vitamins
  • Synthesis of plasma proteins, glucose, ketone bodies, cholesterol, fatty acids and amino acids
19
Q

What occurs in zone I of hepatocytes

A
  • Peiportal
  • Amino acid catabolism
  • Gluconeogenesis
  • Cholesterol synthesis
20
Q

What occurs in zone III of hepatocytes

A
  • Lipid synthesis
  • ketogenesis
  • glutamine synthesis
  • drug metabolism
21
Q

What are the functions of bile?

A
  • Excretion of waste products (those not easily excreted by the kidneys)
  • Excretion of hormones
  • Excretion of drugs and other xenobiotics (foreign to the body)
  • Secretion of bile acids/salt to aid intestinal lipid digestion and absorption
  • Secretion of electrolytes and water as a vehicle
22
Q

Describe the synthesis of bile acids/ salts

A
  • Syntehesised from cholesterol which is produced by the liver
  • From cholesterol it forms primary bile acids which are weakly ionised, they remain in a protonated state
  • Conjugation with:
    • Taurine
    • Glycine
    • Sulphate
    • Gluronate
  • Makes them more water soluble and charged hence (bile salts)
  • Dehydroxylation by bacteria in the terminal ileum and colon recycled back into liver
23
Q

Explain the apical secretion of bile salts

A
  • Unconjugated and conjugated bile salts are secreted via:
    • Bile export pump (BSEP)
    • Multidrug resistance associated protein 2 (MRP2)
    • Both are ABC transporters
24
Q

What are ABC transporters?

A
  • ATP binding casette transporters
  • Huge family pumps using ATP hydrolysis to import or export wide range of substrates
  • Alternating access mechanisms, powered by ATP hydrolysis
25
Q

Explain how bile acids and salts are reabsorbed in the SI

A
  • Slow, passive reabsorption of unconjugated bile salts along the intestines
  • Active uptake of conjugated bile salts in the terminal ileum via sodium - bile salt co transport and organic solute transporter
26
Q

Describe the basolateral uptake of bile acids/salts

A
  • Uptake of recycled bile salts via:
  • Co-transport with sodium via sodium taurocholate co-transporting peptide (NTCP)
  • Exchange with chloride via organic anion transporting peptide (OATP)
  • Also simple diffusion of unconjugated, neutral bile salts
27
Q

Explain how bilirubin is formed and excreted!

A
  • Breakdown of haem to bilirubin following phagocytosis
  • Carried by albumin to the liver (not water soluble) taken up via OATP
  • Conjugation with glucuronate in ER and secretion via MRP2
  • Intestinal bacteria deconjugate bilirubin and convert it to urobilinogen (colourless)
  • Some reabsorbed and excreted as urobilin (yellow) via kidney
  • Some further converted to stercobilin (brown) in colour
28
Q
A