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| Departments » Medical Sciences » Biochemistry » Answers |
Answers to Biochem Questions
1.) Explain how hormones can be considered to be of two different types of chemical structure.
The term hormone essentially means any substance in an organism that carries a signal to generate some alteration at the cellular level. Hormones can be divided into the broad classes of water-loving (hydrophilic) and fat-loving (lipophilic).
Hydrophilic hormones are not fat soluble and cannot cross cell membranes on their own, they require some form of transport mechanism. This means that hydrophilic hormones require receptors on the cell membrane.
Lipophilic hormones are fat soluble and can cross the cell membrane by themselves. The receptors for these hormones are usually found on the cell nucleus.
Hormones in some instances can also act as neurotransmitters released by neurons at synapses. For example noradrenaline and adrenaline in the heart.
Another classification system suggests there are three chemical structures of hormones: those that contain peptide bonds (peptides or proteins); those derived from cholesterol (steroid hormones, and derivatives of Vitamin D); and those arising from the amino acid tyrosine (catecholamines and thyroid hormones).
2.) What are the interrelationships between folate and vitamin B12?
The methylation of homocysteine depends on methylcobalamine (a B12 derivative) and N5-methyl-THF (a folate derivative), and this is the only mammalian reaction known to require both vitamins. The details of this reaction are explained in the next question.
Devlin suggests that B12 may also be required for uptake of folate by cells, and for its conversion to the biologically more active polyglutamate forms.
3.) What is the methyl trap hypothesis?
The methylation of homocysteine produces methionine. This reaction is dependant on methylcobalamine, N5-methyl-THF, and the enzyme methionine synthase. In the reaction N5-methyl-THF is converted to THF from which it can be converted to other forms (N5N10-methylene-THF, N5N10-methenyl-THF, N10formyl-THF). In the absence of methylcobalamine N5-methyl-THF cannot be reconverted to THF.
N5-methyl-THF is formed from N5N10-methylene-THF a reaction which occurs strongly in one direction in vivo. The enzymes that catalyse this reaction are inhibited by S-adenosylmethionine (SAM) which is dependent on the formation of methionine. Thus as the concentration of methionine drops the concentration of SAM drops and the enzyme that converts N5N10-methenyl-THF to N5-methyl-THF increases its activity. Thus more and more folate is trapped in the N5-methyl-THF form.
It can be seen then that the absence of B12 creates the ‘methyl-trap’ in two ways: firstly it does not allow N5-methyl-THF to be converted to THF; and secondly, it permits more N5-methyl-THF to be created from N5N10-methenyl-THF owing to a drop in the production of SAM.
4.) How might folate and vitamin B12 relate to anaemias?
There are two forms of anaemia associated with folate and B12 deficiency: megaloblastic and pernicious.
Megaloblastic anaemias are defined as anaemias characterised by a common morphology of gigantism of all reproducing cells. This is produced by a common underlying biochemical defect of slowed DNA synthesis. Anything that slows DNA synthesis produces megaloblastosis, but more than 95% of cases turn out to be due to deficiency of vitamin B12, folate or both.
In the absence of folate, purines needed for DNA synthesis cannot be formed.
Adult pernicious anemia is an autoimmune disease which results from the malabsorption of B12. Clinical manifestation of B12 deficiency is a megaloblastic anaemia closely resembling that of a folate deficiency. However, if it is treated as a folate deficiency, only short term improvements will be observed. This is because the folate is subject to the methyl trap described in question 3. As a result the symptoms of this form of anaemia will recur until B12 is supplemented.
5.) Explain the biosynthesis of catecholamines.
The catecholamines include dopamine, noradrenaline, and adrenaline. They are all formed from the amino acid tyrosine. They can act as both hormones and neurotransmitters.
The formation of catecholamines occurs in four stages:
Stage 1
In the presence of tetrahydrobiopterin, Oxygen (O2), Iron (Fe2+), and NADPH, a hydroxide molecule is added to the L isomer of tyrosine with the assistance of the enzyme tyrosine hydroxylase. This reaction occurs within the cytosol of catecholaminergic nerve terminals and the adrenal medulla. 3,4 dihydroxy-L-phenylalanine (L-dopa) is produced by this reaction.
Stage 2
In the presence of the enzyme DOPA decarboxylase and the coenzyme pyridoxal phosphate, L-dopa has a COO- group removed (decarboxylisation) to produce Dopamine. The reaction occurs in the same location as stage 1.
Stage 3
Dopamine is further modified by the enzyme dopamine b -hydroxylase with the co-factors Carbon, Oxygen and Copper (Cu2+), which add a hydroxide molecule. This creates noradrenaline. The reaction takes place in adrenergic neurons, and adrenal medullary tissue.
Stage 4
Noradrenaline is converted to adrenaline by the enzyme noradrenaline N-methyl transferase and the coenzyme S-adenosyl methionine, through the addition of a methyl group. The enzyme noradrenaline N-methyl transferase is held by the cytosol of a few neurons in the brain and by the chromaffin cells in the adrenal medulla.
6.) Explain the structure of acetyl co-enzyme A, and explain why it is such a crucial molecule in biochemistry.
Co-enzyme A (CoA) is composed of Vitamin B5 (Pantothenic Acid), a molecule of Adenine Tri-phosphae (ATP), and the amino acid cystine. Cystine has an –SH that joins to the acetyl group (COOH) forming acetyl co-enzyme A.
Picture Coming Soon
The structure of Acetyl CoA
Acetyl CoA is important because it links glycosis and the Kreb’s cycle and supplies carbon for fatty acid and steroid synthesis. Without it energy could not be created within the body.
7.) Explain why the metabolism of amino acids is fundamentally different from the metabolism of carbohydrates and fatty acids.
The main difference between amino acids and the other macro-nutrients is the presence of nitrogen. There are no storage forms for nitrogen reserves therefore a maintenance supply of amino acids is required by the body.
Excess amino acids can be oxidised for energy or stored as fat and glycogen; however, in each case nitrogen must be eliminated. A byproduct of this process is ammonia which is very toxic to the body, this usually dealt with in the uric acid cycle.
8.) Distinguish lipogenesis from b -oxidation.
Fats are used as an energy source essentially when our reserves of glucose and glycogen are depleted. b -oxidation involves a cycle of four reactions that removes two-carbon segments from a fatty acid in sequential order to produce acetyl CoA and hence ATP. In each cycle, the b carbon in the fatty acid chain is oxidized, yielding an acetyl CoA unit and a shortened fatty acid chain. The reaction takes place in mitochondria, and the coenzymes NADH and FADH2 are involved.
When the body has met all its energy needs and glycogen stores are full, excess acetyl CoA, which comes from the catabolism of dietary carbohydrates, is converted to fatty acids (lipogenesis). This occurs through a six step reaction cycle that links two-carbon units to a chain with each turn. The cycle repeats until the chain typically contains 16 or 18 carbon units. Lipogenesis is essentially the reverse of b -oxidation. It takes place in the cytoplasm as opposed to the mitochondria, and requires NADPH.
9.) List three substances used as second messengers.
Cyclic AMP (cAMP)
Inositol tri-phosphate (IP3)
Diacylglycerol (DAG)
10.) Briefly explain the second messenger system.
The second messenger system is related to the mechanism of action of Type III receptors which are used by hydrophilic hormones. Type III receptors are ‘transmembrane proteins’ that, upon activation by a hormone, transfer signals to a sub-membrane "guanine nucleotide-binding protein" (G-proteins). These proteins have GDP bound to them. On activation they exchange the GDP for GTP and release themselves from bondage to the receptor protein. The liberated and active G-protein stimulates the formation of a substance within the cell called the ‘second-messenger’. The second messenger then triggers a cascade of reactions within the cell causing metabolic changes.
For example, the second messenger IP3 stimulates the release of Ca2+ ions by binding to receptors in the endoplasmic reticulum of some cells. Ca2+ then causes other reactions to take place. Second and third messengers (refer question 9) are kept at low levels within the cell and they can increase many-fold on the activation of G-protein coupled receptors.