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Biochemistry Flashcards

1
Q

Glycogenesis definition

A

Synthesis of glycogen from glucose

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2
Q

Glycogenolysis definition (2)

A

Breakdown of glycogen to form glucose

Fluctuates dependent upon meal times

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3
Q

Gluconeogenesis definition (2)

A

Synthesis of glucose from precursor substrates (lactate, amino acids, glycerol)
Primary source of glucose when hepatic glycogen is depleted

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4
Q

Main storage forms of glucose (2)

A

Liver glycogen

Muscle glycogen

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5
Q

Liver glycogen use

A

Released to maintain blood glucose levels for RBCs and brain - Glucose 6-phosphate can be dephosphorylated here

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6
Q

Muscle glycogen uses (2)

A

Not available for blood glucose maintenance levels - Glucose 6-phosphate CANNOT be dephosphorylated here
Provides energy via glycolysis and Krebs cycle during exercise

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7
Q

Glycogen structure (4)

A

Polymer of glucose molecules
Joined by alpha 1-4 glycosidic bonds
Branches are introduced by alpha 1-6 glycosidic links
Accomplished from phosphorolysis NOT hydrolysis

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8
Q

Glycogen and Glycogenin (3)

A

Glucose residues can only be added to an existing glycogen chain
A glycogen primer containing at least 4 glucose residues is required
The primer is covalently attached to an enzyme - Glycogenin

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9
Q

Glycogen synthesis pathway (5)

A

Glucose => Glucose-6-phosphate => Glucose-1-phosphate => UDP-glucose => [Glucose]n+1 + UDP

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10
Q

Uridine diphosphate glucose (2)

A

An activated form of glucose

The phosphate ester linkage in UDP (a nucleotide sugar) releases free energy on hydrolysis

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11
Q

Transglycosylase

A

A branching enzyme introducing alpha 1-6 glycosidic branches every 10 glucose residues into glycogen

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12
Q

Glycogenolysis reaction (3)

A

Catalysed by glycogen phosphorylase
[Glucose]n + Pi => Glucose-1-phosphate + [Glucose]n-1 - Rate limiting step of glycogenolysis
One glucose molecule is cleaved off the ends of glycogen at a time

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13
Q

Gluconeogenesis characteristics (6)

A

Occurs in prolonged starvation
Energy is obtained from fatty acid oxidation from adipose tissue
Happens in liver and kidney
IT IS NOT THE REVERSE OF GLYCOLYSIS - Requires unique enzymes to overcome energetically unfavorable steps
Proceeds via the synthesis of oxaloacetate in mitochondria - Vital for accepting acetyl groups from fat breakdown
Rate limiting step by passing pyruvate kinase

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14
Q

Gluconeogensis formula

A

2 pyruvate + 4ATP + 2GTP + 2NADH + 4 H+ + 6H2O

=> glucose + 4ADP + 2GDP + 6Pi + 2NAD+ + 2H+

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15
Q

Cori cycle (Lactic Acid cycle) (6)

A

Lactate is precursor of gluconeogenesis
Blood transports lactate to liver
Liver converts lactate back to glucose
Glucose released into bloodstream
Cycle buys time and shifts metabolic burden from muscle to other organs
Amino acids and glycerol can act as precursors too

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16
Q

Reciprocal regulation (4)

A

High AMP or ADP - Low energy
High ATP - High energy
Fructose 2,6-bisphosphate - High in fed state and low in starved state
Citrate, alanine, acetyl-CoA - High when intermediates or building blocks are abundant

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17
Q

Insulin hormonal regulation effects (3)

A

Promotes glycolysis

Inhibits gluconeogenesis and glycogenolysis

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18
Q

Glucagon hormonal regulation (2)

A

Inhibits glycolysis

Promotes gluconeogenesis

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19
Q

Hormones inhibiting glycogen phosphorylase

A

Insulin

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20
Q

Hormones promoting glycogen phosphorylase (3)

A

Glucagon
Adrenaline
Cortisol

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21
Q

Hormones increasing glycogen synthase

A

Insulin

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22
Q

Hormones decreasing glycogen synthase

A

Glucagon

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23
Q

Rate limiting enzymes in gluconeogenesis (3)

A

Glucose-6-phosphate
Fructose 1,6 biphosphate
PEP carboxykinase

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24
Q

Increased fat intake without appropriate energy expenditure leads to (2)

A

Increase in numbers of adipocytes

More fat in adipocytes

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25
Fat is needed for (3)
Energy source Some PUFAs cant be made in body - Deficiencies can lead to membrane disorders, increased skin permeability, mitochondrial damage Uptake of lipid soluble vitamins A, D, E and K
26
Lipids characteristics (4)
3 types - Simple, compound and steroids Predominantly hydrocarbon Usually contain long chain fatty acids Insoluble in water
27
Triglycerides/Triacylglycerols properties and structure (5)
``` Main energy storage form in adipose tissue Compact - Don’t require storage of water Hydrophobic High energy yield per gram Structure is glycerol with 3 fatty acids ```
28
Fatty acids property and structure (6)
Mainly straight chains Aliphatic (no rings) Usually contain an even number of carbon atoms (2 - 20 or more) Branched chains and odd numbers of carbon are rare Can be saturated, unsaturated, polyunsaturated Double bonds usually in cis configuration
29
PUFAs (4)
More than 1 double bond Only in small amounts but essential Cant be synthesised in body Example is linoleic acid
30
Fatty acids nomenclature (2)
Carbon adjacent to carboxyl group is alpha carbon | Carbon furthest away is omega carbon
31
Fatty acid melting point variation (2)
Fatty acids with 8 carbons are liquid at room temperature - Longer ones are solid Double bonds lower melting point
32
Fat absorption (5)
Main products of fat digestion are glycerol, fatty acids, monoglycerides They are absorbed into mucosal cells of intestine Short and medium-length fatty acids enter portal blood Longer chain FA and monoglycerides are re-synthesised to triglycerides Coated with a layer of protein, phospholipid, cholesterol - Chylomicrons
33
Chylomicrons pathways (3)
Enter lymph, then the blood stream At muscle and adipose tissue, chylomicrons are attacked and cleaved by lipoprotein lipases Free fatty acids are resynthesised into TAGs in adipose tissue or oxidised for energy
34
Lipolysis (2)
Breakdown of lipids | Initial cleavage by hormone sensitive lipases - Releases free fatty acids and glycerol when energy is needed
35
Activation of fatty acid oxidation (3)
Occurs in cytoplasm Requires 2 ATP Fatty acid + CoA => Acyl-CoA
36
Carnitine shuttle (4)
In cytoplasm, fatty acids are transferred from acyl-CoA to carnitine Acyl-carnitine transporter in inner membrane - Facilitates antiport of acyl-carnitine into the mitochondrion and carnitine out Net result is acyl-CoA in mitochondrial matrix Rate limiting step of fatty acid conversion to ATP
37
Beta oxidation (3)
Occurs in mitochondrial matrix 4 steps in each cycle Products are 1 acetyl-CoA, 1 FADH2, 1 NADH + H+, 1 fatty acyl-CoA shortened by 2 carbon atoms
38
Yield of beta oxidation for stearic acid (C18) (5)
Cycle is repeated 8 times - For even numbered fatty acids follows (n/2)-1 8 FADH2, 8 NADH + 8 H+ 9 acetyl-CoA which is oxidised in Krebs cycle - Makes 9 FADH2, 27 NADH + 27 H+, 9 GTP P/O ratio is 1.5 for FADH2 and 2.5 for NADH + H+ Total yield is 17 x 1.5 + 35 x 2.5 + 9 – 2 = 120 ATP (Minus 2 from activation step)
39
Glycerol breakdown (2)
Activated to glycerol-3-phosphate by glycerol kinase | Dehydrogenated to dihydroxyacetone phosphate
40
Ketone bodies production and function
Formed in liver mitochondria from acetyl-CoA from beta oxidation Vital for energy metabolism for heart muscle and renal cortex - Converted back to acetyl-CoA which enters Krebs cycle
41
Ketosis in starvation and diabetes (8)
Oxaloacetate is consumed for gluconeogenesis Fatty acids are oxidised to provide energy Acetyl-CoA is converted to ketone bodies High levels in blood Too much for extrahepatic tissue (heart, brain) Accumulation leads to severe acidosis Impairs tissue function, particularly CNS Smell of acetone can be detected in breath
42
Lipogenesis definition and characteristics (4)
Fatty acid synthesis Occurs in liver, kidney, glands, brain and adipose tissue Takes place during excess energy intake A reductive process as electrons are needed
43
Excess carbohydrates and fatty acids (3)
Conversion to fatty acids and triglycerides in the liver Free fatty acids are transported in plasma bound to albumin Triglycerides are transported to adipose tissue by VLDL for storage
44
Generation and transport of acetyl-CoA for lipogenesis (3)
Generated by pyruvate dehydrogenase complex in mitochondria Inner mitochondrial membrane is impermeable to acetyl-CoA Citrate transports acetyl groups into the cytoplasm - Citrate is formed by condensation of acetyl-CoA with oxaloacetate (1st Krebs cycle step)
45
Malonyl-CoA (2)
Direct precursor of Acetyl-CoA activation - Formed by Acetyl-CoA carboxylase Donates carbon atoms to new lipid
46
Acetyl-CoA carboxylase (2)
Expressed in liver and adipose tissue | Essential regulatory enzyme for Acetyl-CoA activation
47
Fatty acid synthase (4)
Catalyses synthesis of saturated long-chain fatty acids from malonyl-CoA, acetyl-CoA, and NADPH Exists as a single polypeptide chain with 7 distinct enzyme activities Catalyses fatty acid synthesis in 4 steps - Condensation, reduction, dehydration, reduction and release Contains an acyl-carrier protein (ACP)
48
Lipogenesis by fatty acid synthase (5)
Using acetyl-CoA and malonyl-CoA as precursors, one cycle of reactions adds 2 carbon atoms to the growing acyl chain Derived from malonyl-CoA Growing acyl chain is attached to ACP Requires NADPH as electron donor When a length of C-16 is reached, the fatty acid is released
49
Essential enzyme in regulating fatty acid synthesis and degradation
Acetyl-CoA carboxylase
50
Acetyl-CoA carboxylase regulation (4)
Insulin signals fed state - Stimulates fuel storage and protein synthesis Glucagon signals starved signals (epinephrine signals required for energy) - Mobilizes glycogen stores Citrate levels are high when acetyl-CoA and ATP are abundant Antagonised by palmitoyl-CoA - Abundant in fatty acids excess
51
Triglyceride synthesis requirements (4)
Requires glycerol-3-phosphate Liver produces G-3-P from glycerol Adipose tissue produce G-3-P from glucose - Only during fed state Involves esterification
52
Where and why are amino acids degraded (2)
Occurs in liver | Due to no storage form for amino acids if not used as building blocks
53
Protein turnover (3)
Damaged proteins have to be removed Tightly regulated by AMP kinase Takes place at various rates
54
Amino acids and nitrogen (2)
Amino acid breakdown produces ammonia (NH3) and ammonium ions (NH4+) NH4+ is toxic at high concentrations
55
Major nitrogen-containing excretory molecules (4)
Urea Uric acid Creatinine Ammonium ion
56
Synthesis of urea steps (3)
Transamination Deamination Urea cycle
57
Transamination (3)
Aminotransferases move the amino group from alpha-amino acids to alpha-keto acids - Usually alpha-ketoglutarate giving glutamate For transport to liver, amino group of glutamate is transferred to pyruvate, giving alanine or glutamine synthase adds NH4+ to glutamate giving glutamine Alanine and glutamine are major carriers of nitrogen in the blood to liver
58
Deamination (3)
Occurs in liver Amino group of glutamate is converted to free ammonium ion Urea is synthesised in complex reactions - One nitrogen from free ammonium, the other from aspartic acid and carbon from CO2
59
Identify precursors of urea cycle (2)
Ornithine | Carbamoyl phosphate
60
Urea cycle overall reaction
CO2 + NH4+ + Asperate + 2H2O => Urea + 2ADP +2Pi + AMP + PPi + Fumarate
61
Fumarate in urea cycle function
Its conversion to malate enables its carbon to be transported back to the mitochondrial matrix via malate-aspartate shuttle
62
Degradation of carbon skeletons of amino acids
After alpha amino group removal remaining carbon skeleton are converted to glucose or oxidised in Krebs cycle
63
Ketogenic amino acids (2)
Degraded to acetyl-CoA or acetoacetyl-CoA | Gives rise to ketone bodies or fatty acids
64
Glucogenic amino acids (2)
Degraded to pyruvate or Krebs cycle intermediates | Can be converted into phosphoenolpyruvate (PEP) and then glucose
65
Alcaptonuria disorder
Degradation of phenylalanine and tyrosine is blocked
66
Maple syrup urine disease (4)
Degradation of valine, isoleucine, and leucine is blocked Urine smells like maple syrup Causes mental and physical retardation Prevented by appropriate diet
67
Phenylketonuria disorder (3)
Phenylalanine accumulates in all body fluids Leads to severe mental retardation Therapy is low phenylalanine diet
68
Urea cycle disorders (4)
Caused by defect in urea cycle enzyme Leads to accumulation of urea cycle intermediates and glutamine in circulation Alpha-ketoglurarate is no longer regenerated as levels become too low to fix more free ammonium ions Treatment is gene therapy, low-protein diet or drugs that remove nitrogen by forming complexes
69
Glycogen synthase (5)
``` Synthesises glycogen from UDP-glucose Adds one glucose molecule to glycogen at a time Can only extend the chains of glycogen Can not introduce branches Rate limiting enzyme of glycogenesis ```

Gastroenterology (11 decks)

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