Biochemistry Flashcards
For metabolism of triglycerides: Where does fatty acid synthesis and activation occur?
In the cytoplasm
How is a dietary fatty acid activated
Addition of a acyl- CoA to form fatty acyl CoA
What must be added to a fatty acyl-CoA for it to enter the mitochondira?
acyl- carnitine group
Where does beta oxidation occur?
In the mitochondia
WHat is the only percursor for fatty acid synthesis?
Malonyl CoA which is formed from acetyl CoA which is formed from citrate in the TCA cycle
What is the main storage form of lipids in the human body?
Triglycerides
Can lipids contain other organic molecules?
Yes, carbohydrates- glycolipid
Prtein- apoprotein
Phosphate- phospholipid
Can fatty acids be used for gluconeogeenisis?
No
What is the first step of fat metabolism?
Lipolysis
Where does beta oxidation occur?
The mitochondrial matrix
How many steps in the beta oxidation cycle?
4 steps in each cycle
What are the products of each beta oxidation cycle?
1 acetyl-CoA
1 FADH2
1NADH + H+
1 fatty acyl-CoA shortened by 2 carbon atoms
How often does beta oxidation happen for the breakdown of a C16 fatty acid?
(16/2) - 1 = 7 times
Where are ketone bodies formed?
Liver mitochondria under fasting conditions
How are ketone bodies formed?
Fatty acids are oxidised by beta oxidation to form acetyl-Co A which is used to form ketone bodies
Where are ketone bodies found after they have been produced?
Diffuse into the blood stream and peripheral tissue. Important for energy metabolism in the brain, heart muscle and renal cortex during starvation.
What happens to ketone bodies in peripheral tissue during starvation?
Converted back into acetyl-CoA which enters the TCA cycle to produce energy
Why are ketone bodies important for maintaining neurological signals?
The can be used to produce glutamine- a neurotransmitter- form alpha ketogluterate
What are the 3 ketone bodies
Acetoacetate
Acetone
Alpha-3-hydroxy-butyrate
What are the 2 functions of ketones?
Energy production and neurotransmitter synthesis
Are ketone bodies water soluble?
Yes
What can accumulate as a byproduct of beta oxidation under conditions of extreme starvation?
Ketone bodies
What is fatty acid synthesis?
The process which drives lipogenesis
Where does fatty acid synthesis occur?
Mainly in the liver
What happens during fatty acid synthesis?
1) Glucose is used to generate Acetyl CoA.
2) The enzyme Acetyl-CoA Carboxylase converts AcetyelCoA to Malonyl-CoA (the major fatty acid synthesis precursor)
How is Acetyl-CoA Carboxylase activity regulated?
Nutrient and energy status
What are the cofactors in fatty acid synthesis?
NADPH- reductant
What are the cofactors in catabolism of fatty acids (beta oxidation)?
NAD+ and FAD (oxidants)
Which molecules stimulate Acetyl-CoA carboxylase and fatty acid synthesis?
Insulin (signals the fed state). Stimulates the storage of feuls and synthesis of proteins
Citrate stimulates allosterically. Citrate levels are high when Acetyl-CoA and ATP are abundant
Which molecules inhibit acetyl-CoA carboxylase and fatty acid synthesis?
Glucagon- signals the starved state
Adrenaline which signals the requirement for energy
AMP shows a lack of energy
Palmitoyl CoA which is abundant when fatty acids are in excess.
Fatty acid synthesis is a reductive or oxidative process?
Reductive
How do Acetyl CoA groups get from the mitochondia to the cytoplasm for fatty acid synthesis?
Citrate transports the acetyl groups
What is the donor molocule of carbon atoms to a growing fatty acid?
Malonyl-CoA
Where is urea synthesised?
In the liver
How is urea synthesised?
Urea cycle beginning with Carbamoyl phosphate
Where do the nitrogens come from to generate urea?
One is from free ammonium ion and the other is from aspartic acid. Carbon is also needed from CO2
How is urea excreted?
In the urine and in sweat
Carbon skeletons of all the amino acids can enter the TCA cycle. T or F?
True
Which amino acids can be used from glucose?
Glucogenic amino acids
Which amino acids can be fully oxidised in the TCA cycle?
Ketogenic amino acids
Free amonium is toxic. T or F?
True
What is the rate limiting step in glycogen breakdown?
Glycogen -> glucose 1 phosphate catalysed by glycogen phosphorylase
Where does gluconeogenesis take place?
Liver ONLY as it requires 4 unique liver enzymes
Where within the cell does gluconeogenesis take place?
Within mitochondria
Gluconeogenesis requires energy. T or F?
True
What os the TCA cycle intermediate which must be produced for gluconeogenesis to take place?
Oxaloacetate
What is glycogenin?
A protein that sits at the centre of a glycogen polymer and has catalytic activity and can covelently bind up to 4 glucose molecules to itself to form the starting point of a glycogen polymer
What is the role of glycogen synthase?
To add glucose molecules to an existing glycogen chain
What can muscle glycogen be used for?
Energy generation in the muscle cell
What must glucose be bound to before it can be transferred onto glycogen?
UDP
Can glycogen synthase introduce branches into glycogen?
Yes
Liver cells are the only cells to create free glucose from glycogen? T or F
True
Glucose is removed from glycogen as glucose-6- phosphate. True or false?
False- Glucose is first removed as glucose-1- phosphate by glycogen phosphorylase and then converted to glucose-6-phosphate by phosphoglucomutase
What are the principal roles of the liver?
1) Bile production
2) Elimination of unwanted molecules: Metabolism to end products eg urea or excretion into the biliary tree and faeces.
3) Secretion of plasma proteins.
4) Storage of important molecules eg glycogen, iron and vitamins
5) Filtering and detoxification of nutrients and xenobiotics
6) Regulation of metabolism (Carbohydrate and lipid metabolism- glycogen, amino acid metabolism- Urea cycle)
What is a zenobiotic?
A substance found in an organism which is not produced by the organism
Why are the stools of patients with end stage liver disease white?
Conjugated Bilirubin makes stools brown. In end stage liver disease the liver is not breaking down Haem to bilirubin and this means the stool is pale
What are the main plasma proteins produced by the liver?
Albumin
Alpha globulins
Beta globulins
Gamma globulins (basis for immunoglobulins.
How does electrophoresis separate proteins?
By size
What are the main functions of plasma proteins?
1) Maintenance of osmotic pressure in blood vessels (maintains BP and hydration of tissues)
2) Transport of hydrophobic substances
3) pH buffering (amino acid side chains carry charge)
4) Clotting
5) Immunity
What hydrophobic substances are transported by albumin?
Steroids
Free fatty acids
Bilirubin
Cholesterol
What is the function of alpha globulins and give an example?
Transport lipoproteins, lipids, hormones and bilirubin.
Eg ceruloplasmin
What is Retinol Binding protein?
Alpha globulin which transports vitamin A.
What does vitamin A deficiency cause?
Visual impairment
Give 2 examples of beta globulins and what their function is?
Transferrin- transports Fe3+
Fibrinogen- inactive from of fibrin which clots blood.
What is the most abundant plasma protein?
Albumin (50%)
35-45g/l
What are the chemical characteristics of albumin?
Small, negatively charged and water soluble.
What is the main determinant of plasma osmotic pressure?
Albumin
What regulates albumin production?
Hormone- Insulin stimulates albumin production.
What does a low albumin indicate?
Liver disease
Starvation or a low protein diet.
Albumin has multiple binding sites for hydrophobic molecules as it has hydrophobic clefts in globular domains. Does albumin have a high affinity fro hydrophobic substances?
No- low affinity so the molecules can be released.
If has a high capacity due to high concentrations
What hydrophobic substances does albumin transport?
Endogenous lipophilic substances (fatty acids, bilirubin and thyroid hormones) Exogeneous substances (Drugs with a hydrophobic capacity like asprin)
How is iron transported in the blood and stored in the body?
Transported as Fe3+ bound to transferrin
Stored as Fe2+ bound to ferritin.
What is iron used for in the body?
Essenitialcomponent of haemoglobin, myoglobin and cytochrome enzymes.
How is Fe2+ in the liver storage oxidised to Fe3+ for transport?
Cu2+ is reduced to Cu+
How is Copper transported in the blood?
Alpha globulin known as ceruloplasmin which is essential for redox reactions and the use of iron.
What is the disease caused by copper overload?
Wilson’s disease
Which hormones are hydrophobic?
Steroid hormones (derived from cholesterol) and T3/T4 thyroid hormones
How is cortisol transported in the blood?
Cortisol binding globulin
How is thyroxine transported in the blood?
Thyroid binding globulin
What is the function of globulins in hormone transport?
May them soluble so they do not precipitate out of plasma.
Control the distribution and stability of the molecules (hormones are unstable but short lived.) This extends their biological half life and increases their plasma concentration.
What is a lipoprotein?
Molocule with a core of hydophobic lipids (cholesterol esters and triglycerides)
Surrounded by a phospholipid shell with apolipoproteins.
Free cholesterol dispersed throughout
What is the function of lipoproteins?
Fat transport between tissues and organs
Secreted in surfactant in the lungs
What is the function of chylomicrons and where do they origionate?
Transport of exogenous (dietary) fat to the liver
Origin = intestine
What is the function of VLDL and where do they originate?
Transport of endogenous fat to peripheral cells
Origin = Liver
What is the function of LDL and what where does it originate?
Cholesterol transport to peripheral tissues
Origin = VLDL, IDL, Liver
What is the function of HLD and where does it originate?
Reverse cholesterol transport.
Origin = intestine and liver
What si reverse cholesterol transport?
Where HDL removes excess cholesterol from the cells. Cholesterol is esterified with fatty acids and transported back to the liver and excreted as bile salts via bilary system or faeces
Which organ is the only organ to metabolise and excrete cholesterol?
Liver.
Change in liver function effects all steroid hormones produced from cholesterol.
What vitamins does the liver store and roughly how long s the storage?
Vitamin A (retinol palmitate) 10 months
Vitamin D. 3 weeks
Vitamin B12. 3-5 years
Cholesterol is a precursor of which molecules?
Bile acids
Steroid hormones
Vitamin D
What happens to cholesterol in the cell membrane during fever?
Increases as this increases the rigidity of the membrane.
What diseases can cholesterol precipitate?
CVD and gallstones
If you have a diet high in cholesterol (western diet) how will this effect liver de novo cholesterol synthesis?
Reduce denovo synthesis
What percentage of circulating cholesterol is in free form and how is the rest circulating?
30% in free form.
The remainder is esterified into long chain fatty acids (not soluble in water) so it is incorporated into lipoproteins which are soluble.
How is cholesterol stored?
Lipid droplets
What is the basic structure of cholesterol?
Basic 4 ring structure
Which cells can synthesise cholesterol?
All human cells
Main site is the liver (lesser contribution of intestines, adrenal cortex and gonads)
What is required to synthesise 1 mol of cholesterol?
18 mol Acetyl CoA
16 mol of NADPH (for reducing)
36 mol ATP (for energy)
What is the precursor, rate limiting enzyme and final product of cholesterol metabolism?
Precursor = Acetyl CoA
Rate limiting enzyme = HMG- CoA reductase
Final product = Cholesterol (27 carbons)
What does HMG CoA reductase do?
Catalyse the irreversible formation of mevalonic acid.
What stimulates and reduces HMG CoA reductase activity?
Stimulated by fasting.
Inhibited by dietary cholesterol
Which drug inhibits HMG CoA reductase?
Statins
What is the function of vitamin D made from cholesterol?
Regulation of calcium and phosphorus metabolism.
Most abundant in D3 form.
What are the 3 main groups of steroid hormones produced from cholesterol and where are they synthesised?
1) Corticosteriod- adrenal cortex
2) Androgens- tentis
3) Oestrogens- Ovary
NB: All 3 o these orgas can synthesise small amounts of the other hormones
What is the main etabolic product of cholesterol?
Bile salts- saturated steroid nucleus secreted and synthesised by the liver.
How are bile salts recycled?
Enterohepatic circulation
What is the purpose of anion exchange resins and how do they work?
Lower cholesterol.
Resins bind to bile salts and inhibit reabsorption in the enterohepatic circulation => increased bile salt excretion and synthesis of new bile salts.
Concentration of bile in liver decreased => increase in LDL receptors on hepatic cells and uptake of LDL from plasma increased => Lower plasma LDL.
