Biochemistry Flashcards
1
Q
What is glycogen used for in human
A
Storage of carbohydrates
2
Q
What is glycogenesis
A
Synthesis of glycogen from glucose
3
Q
What is gluconeogenesis
A
Formation of glucose from non-carbohydrate sources such as lactate and glycerol
4
Q
Where does glycogen occur
A
Liver and muscle cells, same structure different function
5
Q
Use of glycogen in liver
A
Broken down between meal to keep up blood glucose levels for RBC and brain
6
Q
Use of glycogen in muscle
A
Can’t be broken down for blood glucose levels, used to provide energy via glycolysis during physical activity
7
Q
What is glycogenolysis
A
Breakdown of glycogen to glucose
8
Q
What organ helps to keep blood sugar levels constant between meal times
A
Liver via glycogenolysis
9
Q
Primary source of glucose overnight
A
Gluconeogenesis, only when hepatic glycogen depleted
10
Q
First step in glycogen synthesis
A
Glucose - (hexokinase) to Glucose-6-phosphate
11
Q
How is glycogen chain elongated
A
Glycogen consists of branches and sticks one glucose from UDP-glucose molecules onto this chain to increases size of glycogen.
12
Q
What is the activated form of glucose
A
UDP-glucose, glucose transfer molecule
13
Q
What catalyzes glycogen from UDP-glucose
A
Glycogen synthase
14
Q
Significance of Glycogenin
A
Substrate involved in converting glucose to glycogen, acts as a primer by polymerising first few glucose molecules. Important as Gycogen synthase can extend existing chains of glycogen, not start new molecules
15
Q
Rate limiting enzyme for glycogenesis
A
Glycogen synthase
16
Q
Function of transglycosylase
A
Introduce alpha 1-6 glycosidic branches in glycogen
17
Q
Enzyme used in Glycogenolysis
A
Glycogen phosphorylase, rate limiting step
18
Q
End product of glycogenolysis
A
Glucose - 1 - Phosphate
19
Q
Which cells can dephosphorylate glucose-6-phosphate
A
Liver and not skeletal muscle cells
20
Q
Hormone stimulating synthesis of Glycogen formation
A
Insulin stimulate Glycogenesis, Glycogen synthase
Occurs when lots of carbohydrates are in blood stream
21
Q
Hormone of starving state
A
Glucagon, signal lack of glucose in blood stream. Stimulate glycogenolysis, glycogen phosphorylase
22
Q
What hormones other than Glucagon stimulate glycogen phosphorylase
A
Adrenaline and Cortisol, existing carbohydrate stores broken down into glucose
23
Q
Precursors for gluconeogenesis
A
Lactate - By skeletal muscle under anaerobic condition
Amino acids - From muscle protein by proteolysis
Glycerol - From triglycerides by lipolysis
24
Q
Where does gluconeogenesis occur
A
Liver and small amounts in kidney
25
First substrate of gluconeogenesis
Pyruvate, 2 to make one glucose
26
Glycolysis vs gluconeogenesis energetically
Gluconeogenesis requires 6 ATP (4 ATP + 2 GTP) to make a Glucose, energetically expensive. Glycolysis generates 2 ATP for each glucose. Hence our body should conduct gluconeogenesis only required
27
How can lactate enter gluconeogenesis
Lactate is a polar molecule. It's produced by the cori cycle as part of anaerobic skeletal muscle respiration from glucose - pyruvate - lactate. This is transported via blood to the liver to enter gluconeogenesis
28
Which amino acids can be used to make glucose, Ketogenic or Glucogenic
Glucogenic amino acids can enter gluconeogenesis via TCA cycle substrates or converted to pyruvate
29
First reaction in gluconeogenesis
Pyruvate to Oxaloacetate
30
What is glycoysis
Breakdown of glucose into pyruvate
31
Glucagon on glycolysis
Glucagon stimulates gluconeogenesis and inhibit glycolysis
32
Insulin on gluconeogenesis
Insulin stimulates gluconeogenesis as plenty of glucose is around
33
High ADP and AMP in cells and gluconeogenesis
High AMP/ADP in cells signals low energy and hence glucose breakdown should be started. This stimulates glycolysis and inhibits gluconeogenesis which is energetically expensive
34
Concentration of fructose 2,6-bisphosphate on gluconeogenesis
High concentrations of fructose 2,6-bisphosphate is found in a fed state, hence glycolysis is favoured at high concentrations
35
High concentrations of citrate, alanine and acetyl-CoA
Precursor molecules of biosynthetic processes, present at high concentration when intermediates for building blocks are abundant. Inhibit glycolysis and stimulate gluconeogenesis
36
How are lipids digested
lingual phase in mouth - Quantitatively unimportant
Gastric phase in stomach - Most importance
Small intestine - Most important, emulsification by bile synthesis by liver, pancreatic lipase, hydrolyses TAGs to monoglyceride and free fatty acids.
37
What helps emulsify lipids
It is the breakdown of large fat globules into smaller, uniformly distributed particles. Helped by bile
38
How are lipid droplets avoided from coming back together after emulsification
Droplets are stabilised by addition of amyopathic coat consisting of - certain products of lipid digestion, monoacylglycerols, cholesterol and bile salts
39
What are triacylglycerols converted to
Diglycerols and fatty acids
40
Function of free fatty acids produced as a result of emulsification in the stomach
Free fatty acids stimluate CCK release from duodenum and secretion of pancreatic lipase
41
Function of HCO3- in succus entericous
Neutralize stomach acid and provide suitable pH for optimal enzyme action
42
Where does main lipid digestion occur
At the duodenum by pancreatic lipase, main digestive enzyme in adults
43
What can failure to secrete bile cause
Lipid malabsorption (steatorrhoea) and secondary vitamin deficiency (A,D,E,K)
44
Function of co-lipase
Bile salts inhibit access of pancreatic lipase to triglycerides. Co-lipase binds to bile salts and brings lipase in close contact with tri and diglycerids, where lipase can break it down.
45
Gastric lipase breakdown of lipase
Triglyceride = Diglyceride + Free fatty acids
46
Pancreatic lipase breakdown of lipase
Triglyceride = 2-monoglyceride + 2 fatty acids
47
How are short (<6) and medium (8-12) fatty acids absorbed
Diffused through enterocyte, exit basolateral membrane and enter the villus capillaries
48
How are long (> 12) fatty acids and monoglycerides absorbed
They enter the apical membrane of enteroctyes by passive diffusion and are resyntheized to triglycerides in the endoplasmic reticulum. They are incorporated into chylomicrons subsequently and carried in lymph vessels to systemic circulation via thoracic duct.
49
What happens to the chylomicron after entering systemic circulation
Chylomicron triglycerides metabolised in capillaries (muscle and adipose mostly) by lipoprotein lipase on endothelial cells. Free fatty acids and glycerol released bind to albumen and taken up by tissue
50
What enzyme on epithelial cells of capillaries metabolises chylomicrons
Lipoprotein lipase
51
Where does chylomicron remnant undergo endocytosis
Hepatocytes to be stored, secreted unaltered in bile and oxidised to bile salts
52
What aides in cholesterol absorption
Transport by endocytosis in clathrin coated pits by Neimann-Pick C1 like 1 (NPC1L) protein
53
Mechanism of Ezetimibe
Binds to NPC1L1 protein, prevents internalization and absorption of cholesterol. Used in conjunction with statins in hypercholesterolaemia
54
How is calcium absorbed
Passive paracellular along the length of small intestine.
| Active transcellular mainly duodenum and jejunum.
55
Under what amount is Ca absorption active
< 5 mM of Ca
56
What regulates active Ca absorption
1,25-dihydroxyvitamin D3 (calcitriol) and parathyroid hormone which increases synthesis of former
57
Storage form of Iron
Ferratin
58
Major control of Iron absorption
Ferroportin aka SLC40
59
What regulates ferroportin
Hormone hepcidin released from liver when body iron levels are high
60
How is cobalamin absorbed
Cobalamin (B12) is ingested in food. Haptocorin released from salivary glands. Stomach acid releases B12 from food. Haptocorin binds with B12 in stomach. Parietal cells release intrinsic factor. Pancreatic protease digest haptocorin in small intestine releasing B12. B12 binds to intrinsic factor in small intestine. This complex is absorbed in ileum by endocytosis.
61
How are fat soluble vitamins absorbed
A, D, E and K are incorporated into mixed micelles. Passively transported into enterocytes. Incorporated into chylomicrons or VLDL which are distributed by intestinal lymphatics.
62
How are water soluble vitamins transported
In apical membrane similar to monosaccharides, amino acids and di- and tripeptides
63
How is vitamin B9 transported
Folic acid by Na-independant proton-couple folate transporter 1
64
How is vitamin C transported
Ascorbic acid by Na-dependant vitamin C transporter
65
How is vitamin H transported
Biotin by Na dependant multivitamin transporter
66
Can fatty acids be used for gluconeogenesis
No
67
Main storage form of lipids in the body
Triglycerides
68
Lipids are mostly
Hydrocarbon and water-insoluble
69
First step of fat catabolism is
Lipolysis
70
What is lipolysis
Catabolism of triglycerides to fatty acids and glycerol
71
What is activation of fatty acids
Conversion of fatty acids to fatty acyl-CoA
72
Where does lipolysis and activation occur
In the cytoplasm
73
What is beta-oxidation
Conversion of fatty acyl-CoA to acetyl-CoA
74
Formula for how many oxidations occur for even numbered saturated fat
Ex: C16
16/2 - 1 = 7
7 oxidation cycles occur
75
Products of one beta-oxidation cycle
1 acetyl-CoA, 1 FADH2, 1 NADH + H+, 1 fatty acyl-CoA shortened by 2 carbon atoms
76
What is formed in the liver under fasting conditions
Ketone bodies from acetyl-CoA by beta-oxidation
77
Function of ketone bodies
Diffuse into the blood stream and to peripheral tissue. Important molecules of energy metabolism for brain, heart muscle and renal cortex, it's converted back to acetyl-CoA which enters TCA cycle
78
Major fatty acid precursor
Malonyl-CoA
79
What regulates acetyl-CoA carboxylase activity
Nutrient and energy status
80
What converts acetyl-CoA to malonyl-CoA
Acetyl-CoA carboxylase
81
What stimulates acetyl-CoA conversion by acetyl-CoA carboxylase to malonyl-CoA
Citrate, levels of this are high when acetly-CoA and ATP are abundant. Insulin signals fed state hence stimulates storage of fuels and synthesis of proteins
82
What signals the starved state
Glucagon
83
Is fatty acid synthesis oxidative or reductive?
Reductive
84
What transports acetyl groups from mitochondria to cytoplasm
Citrate
85
What donates carbon atoms to a growing fatty acid
Malonyl-CoA
86
Where is urea synthesized
Liver via urea/ornithine cycle
87
One nitrogen of urea is derived from
Aspartate and other from free ammonium
88
Rate limiting step in glycolysis
Glycogen phosphorylase mediated glycogen to glucose-1-phosphate breakdown
89
What converts glucose-1-phosphate to glucose-6-phosphate
Phosphoglucomutase
90
Fate of glucose-6-phosphate
Glycolysis or transport into blood via GLUT2 in liver as glucose, mediated conversion by glucose-6-phosphatase
91
How does gluconeogenesis proceed
Synthesis of oxaloacetate in mitochondria, TCA cycle intermediate that accepts acetyl groups from fat breakdown
92
What is glycogenin
Protein that sits at the center of glycogen polymer.
93
Function of glycogenin
Catalytic activity, covalently binds four glucose molecules to itself, forming starting point of glycogen polymer.
94
Why is glycogenin significant
Glycogen synthase can only add glucose residues to existing glycogen chains. Glycogenin provides this chain for glycogenesis to occur
95
What forms can pyruvate enter the TCA cycle
As acetyl-CoA or oxaloacetate
96
Can amino acids be synthesized in the TCA cycle
Yes
97
Can muscle glycogen be used as blood glucose
No, only liver glycogen can
98
What does glucose have to be bound to before it can be transferred onto glycogen
Uridine diphosphate glucose (UDP)
99
Precursors for gluconeogenesis
Lactate, glycerol and glucogenic amino acids
100
Glucagon and gluconeogenesis
Glucagon stimulates it, insulin inhibits
101
What do catabolic pathways do
Breakdown reduced substrates for energy generation
102
What provides reducing force in anabolism
NADPH
103
Is catabolism oxidative
Catabolism is oxidative whereas anabolism is reductive
104
Which pathway generates cofactors which can drive oxidative phosphorylation
Catabolic pathways
105
How many ATP and NADH + H+ produced per glucose molecule in glycolysis
2 ATP and 2 NADH+ per glucose molecule broken down
106
What is glycolysis
Breakdown of glucose to pyruvate
107
What does pyruvate have to be converted to before it enters the TCA cycle
Acetyl-CoA
108
Does TCA cycle consume NADH and FADH2
No
109
Does the TCA cycle provide precursors for gluconeogenesis
Yes
110
First substrate of gluconeogenic pathway
Pyruvate, converted in the cori cycle from lactate
111
TCA cycle overview
Two carbon unit (from acetyl-CoA) condenses with four carbon unit. This six carbon unit is decarboxylated twice, yielding CO2. 4 oxidation reactions occur yielding 3 NADH + H+, 1 FADH2 and 1 GTP
112
Electron transport chain is located at
Inner mitochondrial membrane
113
Where are electrons gotten from to reduce O2 to H2O in oxidative phosphorylation
NADH and FADH2
114
What is energy of reduction used for in oxidative phosphorylation
To pump protons from mitochondrial matrix to intermembrane space. This creates a proton concentration gradient. Protons flow back across the membrane. This energy of proton flow is used to phosphorylate ADP to ATP
115
What is the P/O ratio
Number of ATP formed per oxygen atom reduced
116
What relates to the free energy change of a reaction
Difference in redox potentials between substrate and product of a redox reaction
117
What does a more negative redox potential mean
More likely to donate an electron
118
What has a lower redox potential, NADH or FADH2
FADH2, hence NADH likes to donate electrons more
119
Transferring electrons from negative to positive redox does?
Releases energy
120
What can be used to separate immunoglobulins
Electrophoresis; separates by size
121
Main function of plasma proteins
```
Maintain oncotic or colloid osmotic pressure
Transport hydrophobic substances
pH buffering
Enzymatic
Immunity
```
122
Retinol binding protein
Alpha globulin, transport vitamin A which is converted to retinaldehyde. This is part of rhodopsin, a visual pigment
123
Deficiency in what globulin leads to visual impairment
Alpha globulin
124
Deficiency in what globulin indicates iron deficiency
Beta globulins as it helps transport Iron
125
Globulin in fibrinogen (inactive form of fibrin)
Beta globulin
126
Most abundant plasma protein
Albumin
127
Main protein determinant of plasma oncotic pressure
Albumin
128
What hormone from the pancreas stimulate albumin production
Insulin
129
Starvation/ low protein diet causes a decrease in what plasma protein
Albumin
130
How can albumin transport hydrophobic substances
Albumin has multiple binding sites for hydrophobic molecules. Hydrophobic clefts in globular domains that have low affinity but high capacity due to high concentration.
131
What endogenous lipophilic substances does albumin transport
Fatty acids
Bilirubin
Thyroid hormone
132
How is iron transported in the body
As ferric iron Fe3+ bound to transferrin
133
How is copper transported in the body
Bound to ceruloplasmin
134
Deficiency of copper transport causes
Wilson's disease
135
How are thyroxine and cortisol transported in circulation
Thyroid-binding globulin
| Cortisol-binding globulin
136
How do transport globulins increase plasma concentration of hormones and their half life
Transport globulins allow circulation around the body. Without them, the hormones would be eliminated rapidly by the kidney or liver.
137
What aides fat transport in the body
Lipoproteins
138
Structure of lipoproteins
Hydrophobic core of lipids - Cholesterol esters and triglycerides. Surrounded by a shell of polar lipids (phospholipids) and apoproteins. Unesterified/free cholesterol dispersed throughout
139
Lipid transport in dietary vs synthesized fat
Dietary fat - Chylomicrons whereas synthesized fat is transport via vLDL
140
Receptors on hepatocytes for HDL
Scavenger receptors
141
Only organ capable to metabolising and excreting cholesterol
Liver
142
How is cholesterol excreted from body
As bile salts via biliary system or in faeces
143
What vitamins does the liver store
Vitamin D - 3 weeks worth
A - 10 months worth as retinol palmitate
B12 - Few years worth
Iron - From breakdown of haemoglobin, stored associated with ferritin
144
Important compounds made from cholesterol
Vitamin D, steroid hormones and bile salts
145
Cholesterol is insoluble in water. How is this solubilised
Cholesterol is incorporated into lipoproteins and thereby solubilised.
146
Starting substrate for cholesterol
Acetyl-CoA * 2
147
Rate limitng enzyme in synthesis of cholesterol
HMG-CoA catalyzing the irreversible formation of mevalonic acid
148
What stimulates activity of HMG-CoA
Fasting and starvation
149
What reduces HMG-CoA activity
Dietary cholesterol and high intrahepatocyte cholesterol.
150
This compound made from cholesterol has a role in the regulation of Calcium and Phosphorous metabolism
VItamin D
151
Most abundant form of vitamin D in the circulatory system
Vitamin D3
152
Steroid hormones synthesized from cholesterol and the organs responsible
Corticodsteroids - Adrenal cortex
Androgens - Testis
Estrogen - Ovary
153
Can the three steroid organs secrete steroid hormones mainly secreted by the other
Yes, upto a small amount
154
Main metabolism product of cholesterol
Bile salts
155
How can cholesterol excretion be therapeutically manipulated
Anion exchange resins bind bile salts and inhibit reabsorption of bile salts into enterohepatic circulation.
Increase bile salt excretion - increased synthesis of bile salts - concentration of cholesterol in liver decreased as cholesterol is used to synthesize bile salts - number of LDL receptors of hepatic cells increases - uptake of LDL cholesterol from plasma increases
156
Example of anion exchange resin used to bind to bile salts and inhibit reabsorption of bile salts
Cholestyramine
