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Mechanisms Flashcards

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1
Q

G6PD is found in what pathway?

A

Pentose phosphate pathway

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2
Q

Alcoholic liver damage is caused by which 3 compounds?

A

Acetaldehyde, Acetyl-CoA and NADH

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3
Q

Chronologically, what are the 3 diseases of the liver caused by alcohol abuse?

A

Fatty liver

Liver cirrhosis

Alcoholic hepatitis

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4
Q

What drug can be given to an alcoholic?

What is its MOA?

A

Disulfiram. It is a aldehyde dehydrogenase inhibitor so if patient drinks alcohol there will be a build of Acetaldehyde- thus get a ‘Hangover’

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5
Q

What cell is superoxide radicals made in?

A

Mitochondria

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6
Q

Name 3 reactive oxygen species

Name 2 reactive nitrogen species

Give their chemical formulas

A

ROS:
Superoxide (O2-)
Hydrogen peroxide (H2O2)
Hydroxyl radical (OH)

RNS:
Nitric oxide (NO*)
Peroxynitrite (ONOO-)

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7
Q

Where are disulfide bonds produced in proteins?

A

Between thiol and cysteine groups

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8
Q

What are 3 endogenous mechanisms of producing ROS + RNS?

A
  1. Electron transport chain
  2. Nitric oxide synthase
  3. NADPH oxidase
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9
Q

In respiratory burst, after nitric oxide has been made by inducible nitric oxide synthase, what is the function of NO*?

A

Nitric oxide joins with superoxide to make peroxynitrite, which causes the respiratory burst of the MO

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10
Q

What is the function and MOA of NADPH oxidase, in the production of ROS?

A

NADPH -> NADP so it oxidises NADPH thus O2 -> O2*- (superoxide). Superoxide then produces H2O2 (hydrogen peroxide) (and ONOO-)

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11
Q

What happens to the hydrogen peroxide produced in respiratory burst?

A

Myeloperoxidase reacts with the hydrogen peroxide and produces hypochlorite which kills the MO.

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12
Q

What enzyme reduces GSSG (oxidised glutathione)?

A

Glutathione reductase

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13
Q

What enzyme oxidises GSH (reduced glutathione)?

Specifically, how does this reaction reduce the number of ROS?

A

Glutathione peroxidase

2H+ and 2e-‘s are released from this reaction which react with H2O2, Hydrogen peroxidase, to form H20, water.

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14
Q

Name 6 molecules that are anti-oxidants

A 
Vitamin C
Vitamin E
Superoxide dismutase (SOD)
Catalase
GSH (reduced glutathione)
NADPH (from the pentose PHOSPHATE pathway)
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15
Q

What is the function of superoxide dismutase and catalase?

A

SOD catalyzes the dismutation of the O2*- to form oxygen and hydrogen peroxide.

Catalase breaks down hydrogen peroxide to form water and oxygen.

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16
Q

What is the function of vitamin E, as a lipid soluble antioxidant?

A

It protects against lipid peroxidation

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17
Q

What is the mode of inheritance of galactosemia?

Name 5 symptoms of galactosemia

A

Autosomal recessive

Symptoms:

  1. Cataracts
  2. Hepatomegaly
  3. Cirrhosis
  4. Kidney failure
  5. Seizure
  6. Vomiting
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18
Q

Are blood sugar levels low of high in Galactosemia?

A

Low (Hypoglycaemia)

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19
Q

In Galactosemia:

Name 3 enzymes that have reduced function - what general effect will this now have?

Name 1 enzyme that has increased function - what effect does this now have?

A

Reduced function:

  1. Galactokinase
  2. Galactose-1-phosphate uridylyltransferase
  3. UDP-galactose epimerase

So more galactose will be broken down to form galactitol.

Increased function:
Aldose reductase so more NADPH is broken down to NADP so more galactose -> galactitol.

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20
Q

What is:

A) Cortisol
B) Growth hormone

Affect on insulin synthesis and insulin degradation?

A

A) Cortisol: increase insulin degradation and decrease insulin synthesis

B) Growth hormone: increase insulin synthesis and decrease insulin degradation (occurs because growth hormone increases endogenous glucose production)

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21
Q

Name 2 ketogenic amino acids that are involved in the Krebs’ cycle.

What molecule do they feed into?

A

Leucine and Lysine both feed into Acetyl-CoA

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22
Q

Name 1 glucogenic amino acid that is involved in the Krebs’ cycle.

What molecule does it feed into?

A

Cysteine

Pyruvate

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23
Q

Name 1 amino acid that is both ketogenic and glucogenic and is involved in the Krebs’ cycle.

What molecule does it feed into?

A

Tryptophan feeds into pyruvate

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24
Q

Describe the transamination of Alanine.

What keto acid is formed?

A

a-ketoglutarate binds to the amino group on Alanine. Alanine aminotransferase, ALT, then uses a-ketoglutarate to funnel the NH2 (amino group) onto Glutamate. Pyruvate (the keto acid) is also made (pyruvate then goes on to make glucose)

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25
Describe the function of AST, Aspartate aminotransferase in transamination.
Oxaloacetate binds to the NH2 (amino group) on Glutamate and Aspartate aminotransferase, AST, uses Oxaloacetate to funnel the amino group onto Aspartate.
26
Name 2 enzymes that are involved in the deamination of other amino acids.
Amino acid oxidase Glutaminase
27
What happens to the ammonia in the kidney?
Directly enters the urine.
28
What is the function of iNOS (inducible nitric oxide synthase)?
Produces high NO* concentration in phagocytes to aid respiratory burst.
29
What is the MOA of Glutaminase? What 2 organs does it work in?
Glutaminase breaks down Glutamine in the liver and kidney to Glutamate and NH3, ammonia.
30
Glycogen synthase and glycogen phosphorylase are both rate limiting enzymes in the regulation of glycogen in the liver and muscles. Name 2 hormones that: A) increase the the synthesis of Glycogen phosphorylase B) decrease the synthesis of Glycogen synthase
A) Glucagon and Adrenaline increase the synthesis of Glycogen phosphorylase. B) Glucagon and Adrenaline decrease the synthesis of Glycogen synthase. (Glucagon and Adrenaline are both involved in de-phosphorylation)
31
What enzyme converts glycogen to glucose-1-phosphate? What bonds do they break?
``` Glycogen phosphorylase (breaks 1-4 glycosidic bonds) Debranching enzyme (breaks 1-6 glycosidic bonds) ```
32
What enzyme converts Glucose-1-phosphate to and from Glucose-6-phosphate?
Phosphoglucomutase
33
What does Glucose-6-phosphatase do in the liver?
Converts Glucose-6-phosphate to glucose
34
As muscles don’t have Glucose-6-phosphatase, what happens to the Glucose-6-phosphate produced?
Undergoes glycolysis to produce pyruvate.
35
Name the transporters found in the liver and muscle that release glucose into the blood.
Muscle - GLUT 4 Transporter | Liver - GLUT 2 Transporter
36
Name 2 enzymes that convert Glucose to Glucose-6-phosphate. Name their sites.
LG - Glucokinase in liver | Hexokinase in most cells
37
Name an enzyme that converts Glucose-1-phosphate to UDP-Glucose
Glucose-1-phosphate uridylyltransferase
38
Name 2 enzymes that convert UDP-Glucose to Glycogen. Name the bonds that they break.
Branching enzyme breaks 1-6 glycosidic bonds | Glycogen synthase break 1-4 glycosidic bonds
39
What is deficient in von Gierke’s disease and McArdle’s disease?
von Gierke’s disease: deficiency in Glucose 6 phosphatase (lead to hepatomegaly) McArdle’s disease: deficiency in muscle Glycogen phosphorylase
40
Name 3 precursors that make glucose in gluconeogenesis
1. Lactate 2. Amino acids 3. Glycerol
41
Name 3 key enzymes in gluconeogenesis. What do they convert?
PEPCK (oxaloacetate -> phosphoenolpyruvate) Fructose-1,6-bisphosphatase (fructose-1,6-bisphosphate -> fructose-6-phosphate) Glucose-6-phosphatase (glucose-6-phosphate -> glucose)
42
Name 2 hormones that increase the amount of PEPCK and increase the amount and activity of fructose-1,6-bisphosphatase.
Glucagon and cortisol
43
What is the function of Human sensitive lipase. Where does it act?
HSL breaks down Triacylglycerol, in Adipose tissue, into FA and glycerol.
44
Where does fatty acid B-oxidation (lipolysis) occur?
In mitochondria
45
Where does fatty acid synthesis occur?
In cytoplasm
46
Name 5 lipoproteins in order of increasing density and protein percentage and decreasing diameter. Also split them into triacylglycerols and cholesterols.
``` Triacylglycerols: 1) Chylomicrons 2) Very Low Density Lipoproteins Cholesterols: 3) Intermediate Density Lipoproteins 4) Low Density Lipoproteins 5) High Density Lipoproteins ```
47
How do lipoproteins get back into the liver? Give the LDL example.
Via receptor mediated endocytosis. LDL’s have ApoB-100 molecule on their surface and cell membranes in the liver have ApoB-100 receptors on it.
48
Once lipoproteins have entered the liver, how do they undergo lysosomal degradation?
Lysozyme vesicles fuse with the vesicle that contains the lipoproteins
49
What are reticulocytes? What type of genetic material do they have?
They are immature RBCs that have rRNA
50
Name 2 positive influences and 2 negative influences of non-haem (ferrous iron (Fe2+) and ferric iron (Fe3+)) absorption.
Positive influences: Vitamin C Citrate Negative influences: Tannins (tea) Antacids
51
Name 2 storages of ferric iron
Ferritin and Haemosiderin
52
Name 4 sites that Haemosiderin accumulates in
Bone marrow Macrophage Liver Spleen
53
What is excess iron stored as in organs?
Haemosiderin
54
How many a and B globin genes are there in each human? What chromosomes are they found on?
2 alpha globin genes are found on chromosome 16 so there is a total of 4 alpha globin genes in each human. 1 beta globin gene is found on chromosome 11 so there is a total of 2 beta globin genes in each human.
55
If oxygen levels are low, does EPO levels increase or decrease?
Increase
56
Where is the satiety centre in the brain? Name a nucleus that controls appetite and is found in this location.
Arcuate nucleus in the hypothalamus.
57
Arcuate nucleus: What hormone in the primary inhibitory neurone produces a neurotransmitter that promotes satiety (full)? What is the name of the NT?
POMC in the primary inhibitory neurone in the arcuate nucleus produces a-MSH (the NT) (alpha melanocyte-stimulating hormone)
58
Arcuate nucleus: Name 2 hormones in the primary stimulatory neurone that produces neurotransmitters that promote hunger?
NPY (low levels of Leptin stimulate the release of Neuropeptide Y) AgRP
59
Name 4 classes of chemical substances that can act as hormones Which ones are water soluble and/or lipid soluble?
1. Peptide/polypeptides - water soluble 2. Glycoproteins - lipid soluble 3. Amines (a.a derivatives) - lipid soluble (e.g. thyroid hormones) and water soluble (e.g. adrenal medulla hormones) 4. Steroids - lipid soluble
60
Name 3 hormones that are a part of the endocrine system that promote satiety. Where do these hormones come from? Where do they act on? What do they do here?
Insulin from the pancreas stimulates the primary inhibitory neurone in the arcuate nucleus. Leptin from adipose tissue stimulates the primary inhibitory neurone and inhibits the primary stimulatory neurone - both neurones are found in the arcuate nucleus. (High levels of leptin stimulate the release of MSH + CRH) PYY (peptide tyrosine tyrosine) from the SI and colon inhibits the primary stimulatory neurone in the arcuate nucleus.
61
What hormone is the endocrine system promotes hunger? Where does the hormone come from? Where does this hormone act on? What does it do here?
Ghrelin from the stomach wall stimulates the primary stimulatory neurone in the arcuate nucleus. Ghrelin increases growth hormone secretion (AgRP + NPY then release more of its NT’s which then synapse on the 2nd neurone in the arcuate nucleus)
62
Describe the structure of proinsulin
An a helix structure made up of A chain, B chain and C peptide.
63
Fully describe glucagon’s metabolic effect 3
- increases lipolysis in adipose tissue so more glycerol is available for gluconeogenesis and more fatty acids are available to make ketones and triacylglycerols, VLDLC, which is then converted back into FA, by lipoprotein lipases, when they are at a muscle. Liver: - increase glycogenolysis in the liver - increase gluconeogenesis by proteolysis in the liver increasing so there is more a.a. available to be taken up by skeletal muscle for gluconeogenesis
64
What does CRH, ACTH and GnRH stand for? spell properly.
CRH - Corticotropin releasing hormone ACTH - Adrenocorticotropic hormone GnRH - Gonadotrophin releasing hormone
65
Describe the short loop and long loop of the negative feedback of growth hormone secretion.
Long loop: IGFs, insulin like growth factors, inhibits the release of Growth hormone releasing hormone - GHRH - from the hypothalamus and stimulates the release of Growth hormone inhibiting hormone - GHIH - from the hypothalamus, which thus inhibits the release of Growth hormone - GH - from the anterior pituitary gland. Short loop: GH, at high levels, stimulates the release of GHIH from the hypothalamus.
66
Name a GHIH that is released from the hypothalamus.
Somatostatin
67
What is another name for Insulin like growth factors?
Somatomedins
68
Name 2 hormones, released from the hypothalamus, that have an effect on the increased release of prolactin from the anterior pituitary gland. Discuss how they do it.
High TRH, Thyrotropin releasing hormone, and low Dopamine/Prolactin inhibiting hormone levels leads to an increase in prolactin released from the APG.
69
What are the 3 layers of the cortex of the adrenal glands?
Zona glomerulosa Zona fasciculata Zona reticularis
70
What are glucocorticoids effects on metabolism?
1) Increase gluconeogenesis in the liver by increasing proteolysis in SkM, so more a.a. travel to the liver, and by increasing lipolysis in adipose tissue, so more glycerol travels to the liver. 2) Increases fat distribution 3) Increases liver glycogenesis
71
What are the principal cells in the parathyroid gland called and what hormone do they produce?
Chief cells produce parathyroid hormone.
72
What cells in the thyroid gland produce the thyroid hormone? Are these cells found intracellularly or extracellulary?
Follicular cells are found intracellulary.
73
What do thyroid parafollicular cells produce?
Calcitonin
74
What is the function of thyroid colloid cells? Are these cells found intracellulary or extracellulary?
Colloid cells store thyroglobulin and are found extracellularly.
75
What type of receptor is a thyroid stimulating receptor?
A G protein-class receptor.
76
What G proteins are activated by the activation of TSH Receptors? What is the common cellular response?
Gaq and Gas (Gas>Gaq. Gaq activated at higher TSH levels) Stimulation of thyroid hormone production and release.
77
How are T3 and T4 transported in the blood?
Bound to thyroxine-binding globulin (a protein)
78
Thyroid hormones are lipid soluble. What receptors do thyroid hormones bind onto? Where are these receptors found? What are these receptors bound to?
Thyroid hormones bind on thyroid hormone receptors found bound to hormone response element (a specific promotor region in DNA) in the nucleus.
79
What are the 3 effects of PTH?
1. Activates osteoclasts so more calcium and phosphate is reabsorbed. 2. PTH promotes the activation of Vitamin D in the kidney so more active vitamin D is produced to aid calcium absorption in the gut. 3. PTH increases calcium reabsorption in the kidney (DCT) (urine output thus reduces due to more calcium and water being reabsorbed).
80
What trace element is essential for the activity of glutathione peroxidase?
Selenium
81
What are the progressive steps of energy usage, from energy stores, in the body 6
1) Glucose in plasma 2) Glycogenolysis 3) Gluconeogenesis 4) Lipolysis 5) Ketone bodies 6) Proteins in skeletal muscle break down to produce (ketogenic and glucogenic) amino acids
82
Uncoupling protein 1 is expressed in what tissue? Describe the MOA of UCPs.
Brown adipose tissue. Promote the leakage of protons across the cell membrane so the p.m.f. is reduced and less ATP is produced and more energy is released as heat.
83
Name 2 ketone bodies
Acetone Acetoacetate
84
What is the medical term for abnormally long fingers and toes? This condition is seen in Marfan’s syndrome.
Arachnodactyly
85
In newborns, oxidative phosphorylation is uncoupled in brown adipose tissue, in response to the cold. How is this achieved (4)?
1. In cold weather, Noradrenaline actives Lipase - which forms more FAs. 2. FAs activated UCP1s 3. UCP1 pump H+ back into the mitochondria and dissipate the proton motive force (pmf) from ATP production 4. So the pmf is released is released as heat
86
How does Glucocorticoid drug treatment cause Glucocorticoid Induced Osteoporosis?
High Glucocorticoids in the system thus leads to a reduction in ACTH, LH and FSH being released from the Anterior pituitary gland. Low ACTH means that less Androgens are made in the adrenal glands. Low FSH and LH means that less oestrogen and androgens are made in the gonads. Thus low Androgens and Oestrogen reducing the amount of osteocytes converting to osteoblasts so you get reduced bone formation
87
When osteocytes mature, what cell do they become?
Osteoblasts
88
What vitamin level is found to be low in people with alcohol dependence?
Thiamine - Vitamin B1

MEH (3 decks)

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