Case 5 Flashcards
Describe what happens in the absorptive state?
- 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
What are the end products of glycolysis
- Under aerobic conditions
- under anaerobic conditions
- Aerobic conditions - pyruvate
- Anaerobic conditions - lactate e.g. in muscles
What are the functions of the following receptors:
GLUT2
GLUT4
- GLUT2 - liver
- GLUT4 - adipose tissue
- Facilitate diffusion of glucose into cells, they are on the cell membrane
When glucose is taken up by the liver it is phosphorylated, descrie this process and name all the enzymes involved.
- 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
What is the pyruvate dehydrogenase complex?
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
What is the TCA cycle
- 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
What are excess carbohydrates or proteins in excess of the body’s needs converted to
- Converted to fatty acids by the liver
- Stored as fats (triacyglycerol in adipocytes
Explain the process of using acetyl CoA to make Fatty acids
- 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
Regarding the beta oxidation (catabolism of fatty acids) how much ATP, FADH2, NADH, Acetyl-CoA are produced per 2 carbon molecule.
- FADH2
- 2 ATP
- NADH
- 3 ATP
- Acetyl CoA
- 12 ATP
What is ketoacidosis
- Overproduction of ketone bodies acidifying the blood
What does the body use for an emergency fuel
- 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
What happens to excess amino acids
- 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
Explain amino acid metabolism
- 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
Which transmaninase enzyme is more indicative of liver damage and why?
- ALT is more indicative of liver damage but serum AST is more sensitive because the liver contians larger amounts of AST than ALT
How does ALT work?
- 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