Energy Storage Flashcards
(98 cards)
1
Q
In what form is glycogen stored and where in the body?
A
Stored as granules, in the muscles (intra/intermyofibrillar) and in the liver (within hepatocytes)
2
Q
What is glycogen a polymer of? What is its structure? What are the 2 bond types?
A
Glucose, branched, α-1,4 and α-1,6 glycosidic bonds
3
Q
What are the 4 steps in the pathway of glucose to glycogen synthesis? What are the enzymes that catalyse each reaction (if any)?
A
- Glucose + ATP → Glucose 6-Phosphte + ADP
(catalysed by hexokinase) - Glucose 6-Phosphate ⇔ Glucose 1-Phosphate
(catalysed by phosphoglucomutase)
3.Glucose 1-Phosphate + UTP + H2O → UDP-Glucose + 2 Pi - Glycogen (n residues) + UDP-Glucose → Glycogen (n+1 residues) + UDP
(catalysed by glycogen synthase)
4
Q
When is glycogen broken down? (glycogenolysis)
A
Glycogen is degraded in skeletal muscle in response to exercise and in the liver in response to fasting (or from stress response: “fight or flight”)
5
Q
Is glycogen ever degraded fully?
A
Glycogen is never degraded fully, a small amount of primer is always preserved
6
Q
What are the 3 steps in the degradative pathway of glycogen? What are the enzymes that catalyse each reaction (if any)?
A
- Glycogen (n residues) + Pi → Glucose 1-Phosphate + Glycogen (n-1 residues)
(catalysed by glycogen phosphorylase) - Glucose 1-Phosphate ⇔ Glucose 6-Phosphate
(catalysed by phosphoglucomutase) - Glucose 6-phosphate + H2O → Glucose + Pi (catalysed by glucose 6-phosphatase)
7
Q
What does glycogen phosphorylase do?
A
Attacks the α1,4 bonds. The bonds are subjected to phosphorolysis, not hydrolysis resulting in glucose residues released as glucose 1-phosphate rather than free glucose
8
Q
Which enzyme will be used to break the α-1,6 bond in glycpgen and what will it produce?
A
Debranching enzyme, produces free glucose instead of glucose-1-phosphatase (like with glycogen phosphorylase)
9
Q
What does glucose-6-phosphate do after being produced?
A
The glucose 6-phosphate enters glycolysis and is used to provide energy for exercising muscle
10
Q
What does muscle glycogen represent a store of?
A
Glucose 6-phosphate only used by muscle
11
Q
What is glucose-6-phosphate converted into? Why does this only occur in the liver and not in the muscle?
A
In the liver, glucose 6-phosphate is converted to glucose using glucose 6-phosphatase (absent in muscle)
12
Q
What is the role of glycogen in the liver?
A
Glucose store for all tissues of the body
13
Q
What is the role of glycogen in muscle?
A
Glucose 6-phosphate store, only used by muscle cells
14
Q
What are the rate limiting enzymes for glycogen synthesis and degradation?
A
synthesis = glycogen synthase degradation = glycogen phosphorylase
15
Q
What effect do glucagon and adrenaline have on the activity of glycogen synthase and phosphorylase?
A
synthase = decrease, phosphorylase = increase
16
Q
What effect does insulin have on the activity of glycogen synthase and phosphorylase?
A
synthase = increase, phosphorylase = decrease
17
Q
How do muscle glycogen stores differ from liver stores in terms of effect of hormones?
A
Glucagon has no effect in muscle stores. AMP is the allosteric activator of muscle glycogen phosphorylase but not of liver form of enzyme
18
Q
Are glycogen storage diseases inherited? and how do they arise?
A
yes, arise from deficiency or dysfunction of enzymes of glycogen metabolism
19
Q
What are the 3 enzymes of glycogen metabolism that can be deficient/dysfunction?
A
Glycogen phosphorylase, Phosphoglucomutase, Glucose 6-phosphatase (liver)
20
Q
What can be affected by a glycogen storage disease?
A
Increased/Decreased amounts of glycogen - Tissue damage if excessive storage - Fasting hypoglycaemia (low blood glucose) - Poor exercise tolerance Glycogen structure may be abnormal
21
Q
What is gluconeogenesis? and what is it for?
A
The formation of glucose from sources other than carbohydrates. for glucose-dependent tissues (e.g. CNS)
22
Q
Where is main site for gluconeogenesis?
A
liver and kidney cortex (lesser extent)
23
Q
What are the 3 main precursors for gluconeogenesis?
A
Lactate, glycerol and amino acids
24
Q
Where does the lactate come from for use in gluconeogenesis
A
from anaerobic glycolysis in exercising muscle and red blood cells (Cori cycle)
25
Where does the glycerol come from for use in gluconeogenesis
released from adipose tissue due to breakdown of triglycerides
26
Which amino acid is the main source of glujconeogeneis?
alanine
27
Why can't acetyl-coA be converted into pyruvate?
pyruvate dehydrogenase reaction is irreversible so there is no net-synthesis of glucose from acetyl-coA
28
Which steps of glycolysis are used in gluconeogenesis?
Thee reversible steps, but are irreversibly bypassed
29
How are the phosphorylation of glucose and fructose-6-phsophate bypassed?
by thermodynamically spontaneous reactions catalysed by phosphatases
30
How is the formation of pyruvate from oxaloacetate and formation of phosphoenolpyruvate from oxaloacetate bypassed?
by two reactions driven by ATP and GTP hydrolysis and catalysed by pyruvate carboxylase and phosphoenolpyruvate caroxykinase (PEPCK) respectively
31
Is gluconeogenesis hormonally controlled?
yes as it is a stress response?
32
Where are the major control sites? what are they regulated in response to?
PEPCK and Fructose 1,6-bisphosphatase. regulated in response to starvation, prolonged exercise and stress
33
What are the effects of glucagon/cortisol on PEPCK and Fructose-1,6-bisphosphatase? and overall effect on gluconeogenesis?
PEPCK = increased amount
Fructose-1,6-bisphosphatase = increased amount + activity
Effect on gluconeogenesis = stimulates
34
What are the effects of insulin on PEPCK and Fructose-1,6-bisphosphatase? and overall effect on gluconeogenesis?
PEPCK = decreased amount
Fructose-1,6-bisphosphatase = decreased amount + activity
Effect on gluconeogenesis = inhibits
35
What is the time course of glucose utilisation after eating?
> 2 hr = glucose from food
1 - 10 hr = glycogenolysis
8+ hr = gluconeogenesis
36
What form are TAGs (triaglycerols) stored in and what kind of tissue? When are they utilised and how is the storage and mobilisation controlled?
anhydrous form, in adipose tissue, used in prolonged exercise, stress, starvation and pregnancy, under hormonal control
Storage promotion by insulin
Storage depletion activated by glucagon, adrenaline, cortisol, growth hormone and thyroxine.
37
How are dietary triacylglycerols processed for storage?
Dietary lipids are hydrolysed by pancreatic lipase in small intestine to release glycerol and fatty acids. Glycerol enters blood stream and is transported in chylomicrons to adipose tissue to be stored as TAGs
38
Where does lipogenesis (fatty acid synthesis) take place?
in liver
39
What are the 5 steps in lipogenesis?
Glucose -> pyruvate in cytoplasm (glycolysis)
Pyruvate enters mitochondria and forms acetyl-coA and oxaloacetate which then condense to form citrate
Citrate reenters cytoplasm and cleaved back into acetyl-coA and oxaloaceatate
Acetyl-coA carboxylase produces malonyl-CoA from acetyl-coA
Fatty acid synthase complex builds fatty acids by sequential addition of 2C provided by malonyl-CoA (a C3 complex with subsequent loss of CO2)
40
What is the equation of formation of malonyl-CoA from acetyl-CoA
CH3CO-CoA + CO2 ATP -> CH2(COOH)CO-CoA + ADP + Pi
41
What controls rate of fatty acid synthesis and how is this regulated?
controlled by Acetyl-CoA carboxylase
regulated by:
Allosteric regulation (citrate activates and AMP inhibits)
Regulation by covalent modification of protein structure
Reversible phosphorylation/dephosphorylation (Insulin activates by promoting dephosphorylation / Glucagon & Adrenaline inhibit the enzyme by promoting phosphorylation)
42
Compare fatty acid oxidation
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Fatty acid oxidation:
Cycle of reactions that remove 2C
2C removed as acetyl-CoA
Produces acetyl-CoA
Occurs in mitochondria
Uses separate enzymes
Oxidative - produces NADH and FAD2H
Requires small amount of ATP (activate fatty acid)
Intermediates linked to acetyl-CoA
Regulated by availability of fatty acids in mitochondria
Stimulated by glucagon + adrenalin
Inhibited by insulin
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Fatty Acid Synthesis:
Cycle of reactions that add 2C
2C added s malonyl-CoA
Consumes Acetyl-CoA
Occurs in cytoplasm
Uses multi-enzyme complexes
Reductive - requires NADPH
Requires large amount of ATP (drive process)
Intermediates linked to fatty acid synthase - carrier protein
Regulated by acetyl- CoA carboxylase availability
Inhibited by glucagon and adrenaline
Stimulated by insulin
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43
When does mobilisation of protein reserves occur?
during extreme stress (starvation)
44
Which hormones effect protein synthesis and degradation?
Insulin + growth hormone = increase synthesis (decrease degradation)
Glucocorticoids (eg. cortisol) = decrease synthesis (increase degradation)
45
What is Cushing's syndrome caused by and what does it lead to (in terms of skin)
Excess cortisol, leads to weakening skin structure and formation of striae
46
What are the 9 essential amino acids?
Isoleucine, Lysine, Threonine, Histidine, Leucine, Methionine, Phenylalanine, Tryptophan, Valine
(If Learned This Huge List May Prove Truly Valuable)
47
Which amino acids can the body synthesise?
All the non-essential amino acids
48
Where does C for non-essential amino acid synthesis come from?
Intermediates of glycolysis (C3) Pentose phosphate pathway (C4 + 5) and Krebs cycle (C4 + 5)
49
Where is the amino group provided by?
Other amino acids by transamination of from ammonia
50
Why is the amino group removed from amino acids?
To allow carbon skeleton of amino acids to be used in oxidative phosphorylation
51
What happens to the amino group after being removed?
Incorporated into other compounds or excreted from body as urea
52
What are 2 pathways that facilitate removal of N from AA?
transamination and deamination
53
what is transamination? give a general eq.
the transfer of an amino group from an amino acid to an keto acid forming a new amino acid and a new keto acid
AA1 + KA2 -> AA2 + KA1
Amino acid has R group of keto acid and vice versa
54
What kind of enzymes are used and what is special about them?
aminotransferases and are specific for individual amino acids/similarly structured groups
55
What do aminotransferases use to funnel amino group to glutamate?
α-ketoglutarate is the keto acid used
| alanine + α-ketoglutarate ⇔ pyruvate + glutamate
56
What happens when oxaloacetate is used as keto acid?
converted to aspartate
57
What enzyme and keto acid is used to funnel the amino group to aspartate?
aspartate aminotransferase, oxaloacetate
| aspartate + α-ketoglutarate ⇔ oxaloacetate + glutamate
58
Which coenzyme is required by aminotransferases and what is it derived from?
pyridoxal phosphate, derived from vitamin B6
59
What are the 2 key aminotransferase enzymes (you need to know)?`
```
Alanine aminotransferase (ALT)
Aspartate aminotransferase (AST)
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60
What is tested when ALT and AST levels are measured?
Liver function
61
What occurs in deamination?
Removal of amino group to form free ammonia
62
Where does deamination take place?
In liver and kidney
63
Which enzymes are used to deaminate amino acids?
Amino acid-oxidases, glutaminase, glutamate dehydrogenase
64
What happens to the NH3?
NH3 is converted into ammonium ions and then is converted into urea for excretion
65
Where are D-amino acids found? How do they enter the body?
in plant and bacterial cells, through diet
66
Why can't D-amino acids be used for protein synthesis?
The enzyme converts them to keto acids that are not optically active, so proteins would be structurally abnormal and non-functional.
67
What is glutaminase?
high specificity enzyme that converts glutamine to glutamate + NH3
68
What is Glutamate dehydrogenase?
high specificity enzyme that catalyses:
| Glutamate + NAD+ + H2O ⇔ α-ketoglutarate + NH4+ + NADH + H+
69
What is the NH3 removed from deamination converted into?
into urea which is excreted in the urine
70
What is the overall equation for the urea cycle (ornithine cycle)?
2NH3 + CO2 -> CO(NH2)2 + H2O
71
What happens to the remaining C-skeleton from the amino acid?
converted to one or more of Pyruvate, Oxaloacetate, Fumarate, α-Ketoglutarate, Succinate, Acetyl-CoA
72
What is special about a ketogenic amino acid?
Amino acids that produce acetyl-CoA (e.g. leucine, lysine) as the acetyl-CoA can be used to synthesise ketone bodies
73
What is special about glucogenic amino acids?
Amino acids that produce the other products as they can be used for glucose synthesis by gluconeogenesis
74
Which AAs are both ketogenic and glucogenic?
Isoleucine, threonine, phenylalanine
75
Is urea synthesis regulated? if so, by what?
not really regulated, can only be regulated by presence of enzymes involved (high protein diet induces the enzymes while a low protein diet or starvation represses enzymes)
76
In re-feeding syndrome, why should protein be given gradually? not all in one go?
Since starving individuals = low activity of the enzymes. Too much protein too soon = hyperammonaemia (as excess amino acids are degraded)
77
What do disorders in the urea cycle always lead to?
Hyperammonaemia (high blood NH4+ concentration) and Accumulation and/or excretion of a particular urea cycle
intermediate(s)
78
What is generally the treatment of disorders in the urea cycle?
Treatment usually consists of low protein diets and diets in which the keto acids of the essential amino acids are used to replace the amino acids themselves
79
How do treatments of disorders in the ureas cycle work?
The keto acids are converted to amino acids using some of the NH4+ thereby lowering its concentration in the tissues
80
What is another possibility of the cause of hyperammonaemia (other than urea cycle disorders)
Liver damage (e.g. cirrhosis) - liver’s ability to remove NH3 from the portal blood is impaired
81
How does urea get from liver to urine?
Urea diffuses from the liver cells to the blood and is carried to the kidney where it is filtered and excreted in the urine
82
How can ammonia be reabsorbed into the blood?
small amount of urea may diffuse across the intestinal wall and enter the intestine. Here bacteria may break it down releasing ammonia that can be reabsorbed
83
How can kidney failure lead to hyperammonaemia?
concentration of urea in the blood is high, the production of ammonia from urea by gut bacteria can contribute to the hyperammonaemia
84
What conc should ammonia in blood be kept at?
25-40μmol/L
85
What are the potential toxic effects of ammonia in the blood?
Interference with amino acid transport and protein synthesis, disruption of cerebral blood flow, pH raised, interference of blood-brain barrier, interference with TCA cycle (reacts with α-ketoglutarate to form glutamate in mitochondria)
86
What are the 2 mechanisms utilised for transporting NH3 from tissues for disposal?
Glutamine and Alanine
87
How does glutamine safely transport NH3 from tissues for disposal?
NH3 combines with glutamate -> glutamine, glutamine is transported to liver in blood where it is cleaved by glutaminase = glutamate + NH3, in liver NH3 fed into urea cycle in kidney = excreted directly into urine
88
How does alanine safely transport NH3 from tissues for disposal?
Alanine is formed in peripheral tissues by transamination of pyruvate, alanine transported in blood to liver where it is converted back into pyruvate by transamination, amino group fed via glutamate into urea cycle for disposal as urea whereas pyruvate is used to synthesise glucose which can be fed back into tissue
89
What is phenylketonuria (PKU)?
Accumulation of phenylalanine in tissue, plasma = urine contains large amounts of phenylketones produced from phenylalanine due to deficiency in phenylalanine hydroxylase.
90
What does phenylalanine hydroxylase do?
first step in the metabolism of phenylalanine is its oxidation to tyrosine
91
What can happen to the phenylketones produced by phenylalanine?
metabolised by other pathways to produce various products including phenylpyruvate that is excreted in the urine
92
How is PKU diagnosed and how is it treated?
diagnosed by the detection of phenylketones in the urine or high phenylalanine blood concn (normal is
93
What can happen if it isn't treated?
inhibit brain development due to inhibition of pyruvate uptake by phenylpyruvate which inhibits pyruvate uptake into mitochondria and interferes with energy metabolism in the brain
94
What is Homocystinuria?
Homocystine accumulation and methionine in plasma due to deficiency of cystathionine β-synthase (CBS) enzyme
95
What does cystathionine β-synthase (CBS) do?
converts homocysteine to cystathionine, which is further converted to cysteine
96
How is homocystinuria diagnosed and treated?
usually detected by elevated levels of homocysteine and methionine in plasma and the presence of homocystine (the oxidised form of homocysteine) in the urine. treated with a diet low in methionine
97
What happens without treatment of homocystinuria?
disorders of connective tissue, muscle, CNS and the cardiovascular system
98
What happens in Marfan's syndrome? why can this be confused with homocystinuria?
lack of expression of the protein fibrillin-1 in connective tissues. because the same protein is affected.
