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Y2B2 - Nutrition & Metabolism 📗 > Biochemistry 🧪 > Flashcards

Biochemistry 🧪 Flashcards

1
Q

what is the definition of bioenergetics?

A

study of thermodynamics (energy transformations) in living systems.

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2
Q

energy transformation in cells

A

Cells convert potential energy (energy that has not yet been used), usually in the form of covalent bonds between carbon atoms or in the form of ATP molecules, into kinetic energy (energy in use) to be used.

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3
Q

what is Free energy change (ΔG) = useful energy = gibbs free energy?

A

portion of total energy change in a a system available for doing work

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4
Q

what is the value of Free energy change (ΔG) = useful energy = gibbs free energy?

A

a) May be negative (exergonic)
b) May be positive (endergonic)
c) If there is equilibrium : it is zero

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5
Q

what are the Types of Metabolic Pathways?

A
  • Catabolic (degradation) pathways
  • Anabolic (biosynthesis) pathways
  • Amphibolic pathways
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6
Q

Catabolic (degradation) pathways

A
  • Conversion of large molecules into small molecules, with release of energy, usually as ATP (exergonic)
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7
Q

Anabolic (biosynthesis) pathways

A

Conversion of small molecules into large molecules, This needs energy (endergonic).

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8
Q

Amphibolic pathways

A
  • Cross-roads of metabolism, where both anabolic and catabolic pathways are linked.
  • compounds of krebs cycle are used to form other substances .
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9
Q

what are the stages of oxidation of foodstuffs?

A
  • 1ry metabolism
  • 2ry or intermediary metabolism
  • 3ry or internal respiration or cellular respiration
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10
Q

1ry metabolism

A

Digestion of food into small molecules (glucose, amino acids, and fatty acids) in GIT.

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11
Q

2ry or intermediary metabolism

A

Oxidation of small molecules into CO2, NADH and FADH2 in the mitochondria by Kreb’s cycle.

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12
Q

3ry or internal respiration or cellular respiration

A
  • The NADH and FADH2 carrying 2H enter into the electron transfer chain to produce ATP.
  • This process requires O2 (aerobic conditions) which finally reacts with the 2H to produce H2O.
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13
Q

what is Energy coupling?

A

The living tissue utilize energy liberated from exergonic reaction to synthesize high energy intermediate (mainly ATP) which in turn gives the energy to energy requiring process (endergonic reactions).

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14
Q

state of oxidation In presence of O2 (aerobic condition)

A

Complete oxidation of food takes place in the mitochondria with production of energy (ATP), CO2 and H2O (stage 1, 2, 3).

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15
Q

state of oxidation In absence of O2 (anaerobic conditions)

A

Incomplete oxidation of foodstuffs with production of lower amount of energy (stage 1 and 2 only).

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16
Q

what is the definition of ATP?

A

it is a high energy compound which is considered as the universal energy currency of the cell.

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17
Q

what is the structure of ATP?

A

adenosine triphosphate, a nucleotide formed of :
- Adenine.
- Ribose.
- 3 inorganic phosphates.

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18
Q

what are the mechanisms or types of ATP production?

A

Oxidative phosphorylation: The energy produced in the electron transport chain .

Substrate level phosphorylation: ATP can be formed directly at substrate level.

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19
Q

what is the amount of energy released from hydrolysis of ATP to ADP under standard conditions?

A

Hydrolysis of ATP to ADP (under Standard conditions) releases 7.3 kcal/mol.

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20
Q

how many molecules of ATP are consumed and regenerated for an average person?

A

An average person at rest consumes & regenerates ATP at a rate of approximately 3 molecules per second.

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21
Q

what is the biological importance of ATP?

A
  1. Anabolism
  2. Biosynthesis of cAMP.
  3. Active absorption, secretion and Active transport.
  4. Activation of monosaccharides, FA and AA.
  5. Muscle contraction and Nerve conduction.
  6. Formation of creatine phosphate (muscle energy).
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22
Q

main pathways of glucose oxidation

A
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23
Q

what is the definition of glycolysis?

A

Oxidation of glucose to give :

  • Pyruvic acid in presence of O2
  • Lactic acid in absence of O2
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24
Q

what are the synonyms for glycolysis?

A
  • anaerobic oxidation
  • embden Meyerhof pathway
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25
Q

what is the site of glycolysis?

A

Cytoplasm (cytosol) of all cells.

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26
Q

What are the key regulatory enzymes for glycolysis?

A
  • Glucokinase or hexokinase.
  • Phosphor-fructo kinase 1 (PFK 1)
  • Pyruvate kinase.

Irreversible enzymes

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27
Q

How many steps is glycolysis?

A

10 steps

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28
Q

What is the fate of pyruvate?

A
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29
Q

Energy production in glycolysis

A
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30
Q

Compare between aerobic and anaerobic glycolysis in terms of:
- Site
- End product
- Energy production

A
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31
Q

The regulation of glycolysis

A
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32
Q

What is the biomedical importance of glycolysis?

A

Fluride: Inhibit enolase enzyme —> inhibition of glycolysis in bacteria —>↓↓ lactic acid —-> dental caries

Pyruvate Kinase Deficiency: Inherited deficiency of pyruvate kinase —-> hemolytic anemia because RBCs depend on glycolysis for production of ATP

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33
Q

What is the definition of oxidative decarboxylation?

A

Conversion of Pyruvic acid into Acetyl CO-A.

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34
Q

What is the site of oxidative decarboxylation?

A

Mitochondrial matrix of all tissues except RBC, Severe ms exercise.

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35
Q

What are the enzymes involved in oxidative decarboxylation?

A
  • Dehydrogenase Complex (PDH): multi-enzyme complex Formed of :

Enzymes
1. Pyruvate dehydrogenase (PDH or E1)
2. Dihydro lipoyl transacetylase (E2)
3. Dihydro lipoyl dehydrogenase (E3)

Co-Enzymes
1. TPP = Thiamine pyro-phosphate = Vit B1
2. FAD = Riboflavin = Vit B2
3. NAD = Niacin = Vit B3
4. CoASH = Pantothenic acid = Vit B5
5. Lipoic acid

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36
Q

What is the amount of ATP produced from oxidative decarboxylation?

A

2NADH.H = 2X3 ATP = 6ATP

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37
Q

How many ATP is released from NADH?

A
  • Cytoplasm —->2/3 ATP
  • Mitochondria —-> 3 ATP
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38
Q

What is the definition of Krebs cycle?

A
  • Series of reactions which oxidize acetyl Co-A to CO2, H2O & Energy
  • Hydrogens are transferred to NAD & FAD then to ETC for ATP synthesis
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39
Q

What are the synonyms of Krebs cycle?

A
  • Tri-carboxylic acid cycle (TCA cycle)
  • Citric acid cycle
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40
Q

What is the site of Krebs cycle?

A

Mitochondria of all cells, Except RBCs (No mitochondria)

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41
Q

What is the site of enzymes involved in Krebs cycle?

A

Mitochondrial matrix Except Succinate dehydrogenase (attached to inner membrane).

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42
Q

What is the importance of Krebs cycle?

A

The final common pathway for oxidation of CHO , lipid and protein.

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43
Q

Krebs cycle

A
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44
Q

What are the products of Krebs cycle?

A

1 ATP
1 FADH2
2 CO2
3 NADH.H

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45
Q

Energy produced in Krebs cycle

A
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46
Q

Regulation of Krebs cycle

A
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47
Q

What vitamins play a role in Krebs cycle?

A
  • 4 vitamins of vitamin B complex play role in kreb’s cycle.
  • They act as cofactors for enzymes:
    Riboflavin (FAD)
    Niacin (NAD)
    vitamin B1 (TPP)
    Pantothenic acid (part of CoA)
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48
Q

Summary for complete oxidation of glucose

A
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49
Q

what is the definition of (Hexose monophosphate pathway (HMP) - Pentose shunt)?

A
  • Alternative pathway for glucose metabolism for formation of pentose phosphate
  • Multi cyclic process in which 3 molecules of G-6P give rise to:
    1. 3 CO2
    2. 3 Pentoses
    3. 6 NADPH
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50
Q

what are synonyms of (Hexose monophosphate pathway (HMP) - Pentose shunt)?

A
  • phosphor-gluconate pathway
  • pentose phosphate pathway (PPP)
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51
Q

how much ATP does (Hexose monophosphate pathway (HMP) - Pentose shunt) produce?

A

ATP neither produced nor utilized.

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52
Q

what are the products of (Hexose monophosphate pathway (HMP) - Pentose shunt)?

A
  1. 3 CO2
  2. 3 Pentoses
  3. 6 NADPH
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53
Q

what is the site of (Hexose monophosphate pathway (HMP) - Pentose shunt)?

A

Cytoplasm of Liver, mammary gland, adrenal cortex, adipose tissue, retina, RBCs.

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54
Q

what is the importance of (Hexose monophosphate pathway (HMP) - Pentose shunt)?

A

1. Formation of Ribose 5-P which used in:
- Synthesis of nucleotides & nucleic acids
- Synthesis of Co-enzymes as FAD &NAD

2. Formation of F-6P which used in semen nutrition

3. Formation of NADPH.H which used in:
- F.A synthesis & elongation
- Synthesis of cholesterol , steroid & catecholamine.
- Detoxication reactions.
- Activation of folic acid

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55
Q

regulation of (Hexose monophosphate pathway (HMP) - Pentose shunt)

A

1) G6PD: key regulatory enzyme = rate limiting step.

2) Insulin: induce G6PD & 6 phospho gluconate dehydrogenase → leading to stimulation of HMP.

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56
Q

what is the role of NADPH.H in RBCs?

A
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57
Q

what are HMP disorders?

A

Favism

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58
Q

what is the definition of favism?

A
  • X-linked inherited deficiency of G6PD (more in male)
  • It is the most common enzyme deficiency worldwide.
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59
Q

mechanism of favism

A

↓ G6PD →↓NADPH production →↓reduced glutathione → ↓integrity of RBCs membranes.

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60
Q

what is the clinical picture of favism?

A
  • Most of individual are asymptomatic.

Precipitated by :
1) Ingestion of fava beans.
2) Certain oxidant drugs:
- Antibiotic (Sulfamethazine).
- Antimalarial (Primaquine).
- Antipyretic (Acetaminophen).

3) Certain infections: Release free radicals which damage RBCs.

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61
Q

treatment of favism

A
  • Avoid the predisposing factors
  • Blood transfusion during the attack.
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62
Q

what is the definition of gluconeogenesis?

A

Synthesis of glucose from non- carbohydrate sources.

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63
Q

what is the site of gluconeogenesis?

A
  • Liver (Mainly) & kidney, Intestine

- It requires both mitochondrial and cytosolic enzymes

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64
Q

what is the importance of gluconeogenesis?

A
  • Supply blood glucose in case of CHO deficiency. (Prolonged fasting, starvation & low CHO diet)
  • This is of especial important for tissues requiring continuous supply of glucose as a source of energy (eg: Brain, RBCs, Kidney medulla, Lens, Cornea, Testes, exercising muscle muscle…etc)
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65
Q

steps of gluconeogenesis

A
  • It is not simply reversal of glycolysis.
  • Seven of the reactions of glycolysis are reversible & are shared between glycolysis and gluconeogenesis.
  • Three of the reactions of glycolysis are irreversible
    So, bypassed by special reaction which are unique to gluconeogenesis
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66
Q

what are the reactions unique to gluconeogenesis?

A

Carboxylation of pyruvate to oxaloacetate
- Enzyme: Pyruvate Carboxylase
- Coenzyme: Biotin
————

Oxaloacetate is reduced and transported out the mitochondria to be converted into Phosphoenol pyruvate
- Enzyme: PEP carboxykinase
————

Hydrolysis of Fructose 1,6-diphosphate to F6P
- Enzyme: Fructose 1,6-biphosphatase
————

Hydrolysis of glucose-6-phosphate to Glucose
- Enzyme: Glucose 6-phosphatase

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67
Q

what are the substrates for gluconeogenesis?

A
  • Glycerol
  • Lactate
  • Amino Acids
  • Propionic Acids
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68
Q

how is glycerol released?

A
  • It is released during the hydrolysis of TAG in adipose tissue and released through blood till it reaches the the liver
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69
Q

how is lactate released? And how is it used in gluconeogenesis?

A
  • Lactate is released into the blood by exercising muscle and by cells that lack mitochondria such as RBC
  • Lactate is taken up by the liver and converted to glucose which is released back into the circulation.
  • This cycle is known as Cori cycle.
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70
Q

where are amino acids used for gluconeogenesis derived from?

A
  • Amino acids derived from hydrolysis of tissue proteins, are major source of glucose during a long fast
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71
Q

what are examples of amino acids used in gluconeogenesis?

A
  • Glucogenic amino acid —> α-Keto acids such as oxaloacetate & α-KG.
  • These substrate can enter the TCA cycle and form oxaloacetate, a direct precursor of PEP.
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72
Q

how are propionic acids used in gluconeogenesis?

A
  • Fatty acids with an odd number of carbons produce propoinyl-CoA.
  • It enters the main gluconeogenic pathway via TCA after conversion to succinyl CoA.
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73
Q

regulation of gluconeogenesis

A

- Glycolysis & Gluconeogenesis are reciprocally regulated.

  • Fructose 2,6-biphosphate: Inhibits Gluconeogenesis & Stimulates glycolysis
  • Insulin Inhibits gluconeogenesis
  • Glucagon stimulates gluconeogenesis
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74
Q

what is the storage form of glucose in animals?

A

Glycogen is the storage form of glucose in animals

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75
Q

where is glycogen stored?

A

mainly in liver and Skeletal Muscle

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76
Q

what are the functions of glycogen?

A

Liver glycogen: Maintain the blood glucose level (during the early stages of a fast; between meals)

Muscle glycogen: Serve as a fuel reserve

——
- N.B: Liver glycogen stores are depleted during a fasting

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77
Q

what is the structure of glycogen?

A
  • Glycogen is a branched chain homo polymers of α-D-glucose.
  • The primary glycosidic bond is α (1→4) linkage
  • After an average of 8-10 glucose residues, there is a branch containing α (1→6) linkage
  • Glycogen exist as cytoplasmic granules
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78
Q

what is the definition of glycogenesis?

A

The processes of glycogen synthesis

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79
Q

what is the monomer used in synthesis of glycogen?

A

α-D-glucose

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80
Q

where does glycogenesis take place?

A

Takes place in the cytosol and requires: Uridine triphosphate (UTP) & Energy supplied by ATP

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81
Q

what are the steps of glycogenesis?

A
  1. Synthesis of UDP-glucose
  2. Elongation of glycogen chains
  3. Synthesis of a primer
  4. Formation of branches
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82
Q

Synthesis of UDP-glucose

A

Enzyme: UDP-glucose pyrophosphorylase enzyme

  • The first reaction is between glucose 1-P & uridine triphosphate (UTP) to form UDP- glucose + pyrophosphate
  • [Glucose 6-phosphate is converted to glucose 1-phosphate by Phosphoglucomutase]
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83
Q

Elongation of glycogen chains

A

Enzyme: Glycogen synthase enzyme

  • Transfer Glucose from UDP-glucose to the non-reducing end of glycogen primer.
  • Makes α (1→4) linkages.
  • Cann′t initiate chain synthesis, require glycogen primer (already existing glycogen molecule)
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84
Q

Synthesis of a primer

A
  • If glycogen is depleted a protein, called Glycogenin, gets glycosylated forming short α(1→4) glucosyl chain that serves as a primer (The reaction is catalyzed by glycogenin itself via autoglucosylation)
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85
Q

Formation of branches

A

Branching enzyme: amylo-α(1→4) → α(1→6) transglucosidase

  • Transfer a chain of 6-8 glucosyl residues from the end of the glycogen chain To nearby non-terminal glucosyl residue by an α(1→6) linkage
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86
Q

what is the definition of glycogenolysis?

A

The processes of glycogen degradation

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87
Q

what are the steps of glycogenolysis?

A
  1. Shortening of chains
  2. Removal of branches
  3. Conversion of glucose 1-phosphate to glucose 6-phosphate
  4. Lysosomal degradation of glycogen
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88
Q

Shortening of chains

A

Enzyme: Glycogen phosphorylase enzyme
Coenzyme: Pyridoxal phosphate (PLP) covalently bound to the enzyme

  • Cleaves the terminal α (1→4) glycosidic bond
  • By simple phosphorolysis producing glucose 1- P
  • Until last four glucosyl units before a branch point
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89
Q

Removal of branches in glycogenolysis

A

Debranching enzyme (single protein with two enzymatic activities): Oligo-α(1→4)→α(1→4)-glucan transferase

  • Remove the outer three of the four glucosyl residues and transfers them to the Non-reducing end of another chain
  • Amylo-α(1→6)-glucosidase activity Remove the remaining single glucose residue (attached in an α (1→6) linkage) By hydrolysis releasing free glucose
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90
Q

Conversion of glucose 1-phosphate to glucose 6-phosphate in glycogenolysis

A

Enzyme: Phosphoglucomutase enzyme

  • Liver:
    G-6P is transported into the ER by glucose 6-phosphate translocase. Then, Converted to glucose by glucose 6-phosphatase
  • Muscle: G-6 P enters glycolysis (muscle lacks glucose 6-phosphatase enzyme)
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91
Q

Lysosomal degradation of glycogen

A

Small amount (1–3%) of glycogen is continuously degraded by the lysosomal enzyme, α(1→4)-glucosidase (acid maltase).

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92
Q

what are the key enzymes in regulation of glycogen metabolism?

A

Glycogen synthase & Glycogen phosphorylase

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93
Q

what regulates glycogen metabolism?

A
  • Hormonally regulated to meet the needs of the body as a whole
  • Allosterically controlled to meet the needs of a particular tissue.
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94
Q

allosteric regulation of glycogen metabolism

A

Liver
* In well fed state, Glycogen synthase is activated by G-6-phosphate
* Glycogen phosphorylase is inhibited by G-6-phosphate, ATP and glucose itself

Muscle
* In the muscle; Ca++ and AMP activates glycogen phosphorylase

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95
Q

hormonal regulation of glycogen metabolism

A
  • Insulin: Stimulate glycogen synthesis (glycogenesis) and inhibits its breakdown
  • Glucagon (liver) and Epinephrine (muscle and liver): Stimulate glycogenolysis and Inhibit glycogenesis (cAMP mediated)
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96
Q

what are glycogen storage diseases?

A

Group of inherited disorders characterized by deficient mobilization of glycogen or deposition of abnormal forms of glycogen (GSD)

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97
Q

what do glycogen storage diseases result from?

A

Result from a defect in an enzyme required for glycogen synthesis or degradation

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98
Q

what is the severity of glycogen storage diseases?

A

The severity ranges from mild to severe and fatal

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99
Q

what do glycogen storage diseases affect?

A

May affect single tissue: liver (hypoglycemia) or muscle (muscle weakness), or may be more generalized.

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100
Q

what are the types of glycogen storage diseases?

A
  • Type Ia (Von Gierke’s disease)
  • Type II (Pompe’s disease)
  • Type IIIa Limit Dextrinosis (Cori’s disease)
  • Type IV (Amylopectinosis) (Andersen’s disease)
  • Type V (Mc Ardle’s syndrome)
  • Type VI (Her’s disease)
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101
Q

what is another name for glycogen storage diseases?

A

Glycogenoses

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102
Q

which enzyme is deficient in Type Ia (Von Gierke’s disease)?

A

Glucose 6-phosphatase

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103
Q

what does Von Gierke’s disease affect?

A

Affects liver and kidney (high glycogen in liver & renal tubules)

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104
Q

C/P of Von Gierke’s disease

A

Hypoglycemia, lactic acidemia , Ketosis, hyperlipemia

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105
Q

which enzyme is deficient in type Ib?

A

Glucose 6-phosphate translocase

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106
Q

which enzyme is deficient in Type II (Pompe’s disease)?

A

Lysosomal α-(1-4) & α-(1-6)- glucosidase (acid maltase)

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107
Q

what happens in Type II (Pompe’s disease)?

A

Accumulation of glycogen in lysosome

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108
Q

C/P of Type II (Pompe’s disease)

A

Juvenile onset: Muscle hypotonia & death from heart failure by age 2

Adult onset: Muscle dystonia

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109
Q

which enzyme is deficient in Type IIIa Limit Dextrinosis (Cori’s disease)?

A

Debranching enzyme (liver & Muscle)

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110
Q

what happens in Type IIIa Limit Dextrinosis (Cori’s disease)?

A

Accumulation of characteristic branched polysaccharide (Limit Dextrin)

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111
Q

C/P of Type IIIa Limit Dextrinosis (Cori’s disease)

A

Fasting hypoglycemia, muscle weakness

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112
Q

which enzyme is deficient in Type IIIb Limit Dextrinosis (Cori’s disease)?

A

as Type IIIa but Deficiency of: Liver debranching enzyme. So, no muscle affection )

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113
Q

which enzyme is deficient in Type IV (Amylopectinosis) (Andersen’s disease)?

A

Branching enzyme

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114
Q

what happens in Type IV (Amylopectinosis) (Andersen’s disease)?

A
  • Accumulation of polysaccharide with few branches
  • Early death from heart or liver failure
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115
Q

which enzyme is deficient in Type V (Mc Ardle’s syndrome)?

A

Muscle Phosphorylase

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116
Q

C/P of Type V (Mc Ardle’s syndrome)

A

High glycogen in muscle & Poor exercise tolerance

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117
Q

which enzyme is deficient in Type VI (Her’s disease)?

A

Liver phosphorylase

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118
Q

C/P of Type VI (Her’s disease)

A
  • Hepatomegaly, accumulation of glycogen in liver
  • Mild hypoglycemia
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119
Q

prognosis of Type VI (Her’s disease)

A

generaly, Good prognosis

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120
Q

what is the site of synthesis of cholesterol?

A
  • Cholesterol is synthesized by the cytosol and endoplasmic reticulum of all tissues containing nucleated cells.
  • Most of the biosynthesis of cholesterol occurs within liver cells.
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121
Q

what are the required materials for cholesterol synthesis?

A
  1. Carbon atoms by acetyl-CoA
  2. Energy where the pathway is endergonic, ATP provides energy
  3. Coenzymes: NADPH provides the reducing equivalents
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122
Q

what is the key regulatory enzyme in cholesterol synthesis?

A

HMG CoA reductase

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123
Q

cholesterol regulation

A

Sterol-dependent regulation of gene expression of HMG CoA reductase:
- When sufficient cholesterol is present, transcription of this gene is suppressed and vice versa.

Sterol-accelerated enzyme degradation:
- When sterol levels in the cell are high, it increases the degradation of the HMG CoA reductase enzyme.

Hormonal regulation by covalent modification:
- Insulin and thyroxine activate the enzyme by dephosphorylation
- Glucagon deactivate the enzyme by phosphorylation

Inhibition by drugs:
- The statin drugs are structural analogs of HMG CoA and are competitive inhibitors of HMG CoA reductase. (Statins are used to decrease cholesterol levels in patients with hypercholesterolemia)

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124
Q

what is the definition of ketogenesis?

A

Ketogenesis is the formation of ketone bodies (acetoacetic acid, β- hydroxyl butyric acid and acetone) from acetyl-CoA.

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125
Q

what is the site of ketogenesis?

A

ketone bodies are synthesized exclusively by the liver mitochondria.

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126
Q

what is the source of acetyl CoA in ketogenesis?

A
  • The source of acetyl CoA is B-oxidation of fatty acids in excess of optimal function of Krebs cycle.
  • The acetyl CoA formed from fatty acids can enter and get oxidized to Co2 and water in TCA cycle only when carbohydrates are available.
  • During starvation and diabetes mellitus, the acetyl CoA takes the alternate fate of formation of ketone bodies.
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127
Q

what is the function of ketogenesis?

A
  • Ketone bodies go via blood to extrahepatic tissues where they become oxidized to CO2 and water (ketolysis).
  • Most tissues can more easily oxidize ketone bodies than FAs.
  • Ketogenesis may be considered as a preparatory step performed in the liver to facilitate the oxidation of FA by extrahepatic tissues.
  • Ketogenesis becomes of great significance during starvation (when carbohydrate stores are depleted) and high fat diet when oxidation of fats becomes a major source of energy to the body.
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128
Q

what are the steps of ketogenesis?

A
  • Acetoacetate is the primary ketone body while beta-hydroxy butyrate and acetone are secondary ketone bodies.
  1. Condensation
  2. Production of HMG CoA
  3. Lysis
  4. Reduction
  5. Spontaneous decarboxylation
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129
Q

Condensation (ketogenesis)

A

Two molecules of acetyl CoA are condensed to form aceto-acetyl CoA.

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130
Q

production of HMG CoA (ketogenesis)

A
  • One more acetyl CoA is added to aceto-acetyl CoA to form HMG CoA (beta hydroxy beta methyl glutaryl CoA).
  • The enzyme is HMG CoA synthase. Mitochondrial HMG CoA is used for ketogenesis, while cytosolic fraction is used for cholesterol synthesis.
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131
Q

Lysis (ketogenesis)

A
  • HMG CoA is lysed to form acetoacetate (AAA).
  • HMG CoA lyase is present only in liver.
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132
Q

Reduction (ketogenesis)

A

Beta-hydroxy butyrate is formed by reduction of acetoacetate.

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133
Q

spontaneous decarboxylation (ketogenesis)

A

Acetone is formed (a side product excreted from lungs)

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134
Q

what is the definition of Ketolysis?

A

the complete oxidation of ketone bodies to energy, CO2 and water.

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135
Q

what is the site of Ketolysis?

A
  • Mitochondria of extrahepatic tissues due to high activity of the enzymes: acetoacetate thiokinase and thiophorase, but not in the liver due to deficiency of these enzymes.
  • Tissues like brain can also utilize the ketone bodies as alternate sources of energy, if glucose is not available.
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136
Q

what is the importance of Ketolysis?

A
  • Ketolysis completes the oxidation of FA, which started in the liver.
  • It is a major source of energy to extrahepatic tissues during starvation.
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137
Q

steps of Ketolysis

A
  1. Β-hydroxy butyrate is oxidized to acetoacetic acid
  2. Acetoacetate is activated to aceto-acetyl CoA by thiophorase or thiokinase
  3. Acetoacetyl CoA is lysed to 2 acetyl CoA which enter Krebs cycle.
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138
Q

what is the definition of Ketosis (ketoacidosis)?

A
  • the condition characterized by increased production and circulating of excessive amounts of ketone bodies in blood (ketonemia) and in urine (ketonuria).
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139
Q

Mechanism of Ketosis (ketoacidosis)

A
  • Normally the rate of synthesis of ketone bodies by the liver is such that they can be metabolized by the extrahepatic tissues. Hence, the blood level of ketone bodies is less than 1 mg/dl and only traces are excreted in urine (not detectable by usual tests).
  • When the rate of synthesis exceeds the ability of extrahepatic tissues to utilize them, there will be accumulation of ketone bodies in blood.
  • This leads to ketonemia, excretion in urine (ketonuria) and smell of acetone in breath (fruity odor). All these three together constitute the condition known as ketosis.
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140
Q

C/P of Ketosis (ketoacidosis)

A
  • Metabolic acidosis: Acetoacetate and beta-hydroxy butyrate are acids. When they accumulate, metabolic acidosis results.
  • Reduced buffers: The plasma bicarbonate is used up for buffering of these acids.
  • Kussmaul’s respiration: Rapid deep breathing.
  • Smell of acetone in patient’s breath.
  • Osmotic diuresis induced by ketonuria may lead to dehydration.
  • Coma: due to dehydration and acidosis contribute to the lethal effect of ketosis.
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141
Q

diagnose of Ketosis (ketoacidosis)

A
  • The presence of ketosis can be established by the detection of ketone bodies in urine by Rothera’s test.
  • Urine strip tests based on the same principle are also available.
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142
Q

what is the definition of lipogenesis?

A
  • Lipogenesis is the biosynthesis of triacylglycerol (TG) principally from excess glucose to be stored after a carbohydrate rich meal.
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143
Q

what is the site of lipogenesis?

A

It occurs in most tissues especially adipose tissue, liver, lactating mammary gland and brain.

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144
Q

what are the substrates of lipogenesis?

A

The substrates needed for lipogenesis are: Fatty acid (Acyl-CoA) and Glycerol (Glycerol-3-P), both are derived from glucose.

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145
Q

Processes of lipogenesis

A

Lipogenesis can be divided into 3 processes:
1. Biosynthesis of fatty acids.
2. Biosynthesis of glycerol.
3. Biosynthesis of the triacylglycerol.

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146
Q

what is the building block of Fatty acid synthesis?

A

Acetyl CoA

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147
Q

what are the sources of Acetyl CoA?

A
  1. Oxidative decarboxylation of pyruvate from glycolysis
  2. Oxidation of long-chain fatty acids
  3. Oxidative degradation of certain amino acids
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148
Q

what are the Fates of Acetyl CoA?

A
  1. The acetyl CoA in the mitochondria may be oxidized in Krebs cycle
  2. ketogenesis: synthesize the substances called ketone bodies.
  3. F.A synthesis
  4. Cholesterol synthesis
  5. Synthesis of acetyl choline (neurotramsmitter)
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149
Q

what are the types of fatty acid synthesis?

A

Fatty acids synthesis may be:
1. Cytoplasmic (Extra-mitochondrial) FA Synthesis.
2. Mitochondrial FA Synthesis.
3. Microsomal FA Synthesis.

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150
Q

what is the definition of extra-mitochondrial FA synthesis?

A

This is the only system responsible for de novo synthesis of FA from active acetate (acetyl CoA).

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151
Q

what is the end product of Extra-mitochondrial FA synthesis?

A

Free palmitate (C16) is the main product.

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152
Q

what is the source of Acetyl CoA used in Extra-mitochondrial FA synthesis?

A

The excess acetyl-CoA (from carbohydrate source or less commonly proteins) through the oxidation of pyruvic within mitochondria.

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153
Q

How is acetyl CoA translocated to the cytoplasm?

A
  1. Via Citrate
  2. Via Carnitine
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154
Q

what happens to acetyl CoA after translocation to the cytoplasm?

A
  • Acetyl-CoA molecules are used for palmitic acid synthesis.
  • Oxaloacetate is converted by malate dehydrogenase to malate, Malate then may be converted into pyruvate by malic enzyme, NADPH+H+ is produced, which is essential for FA synthesis.
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155
Q

Translocation of Acetyl CoA via citrate

A
  • Translocation of Acetyl-CoA involves condensation with oxaloacetate to form citrate, which can pass out mitochondrial membrane.
  • In cytoplasm citrate splits again by ATP citrate lyase enzyme into
    Acetyl-CoA and oxaloacetate.
  • Acetyl-CoA molecules are used for palmitic acid synthesis.
  • Oxaloacetate is converted by malate dehydrogenase to malate.
  • Malate then may be converted into pyruvate by malic enzyme.
  • NADPH+H+ is produced, which is essential for FA synthesis.
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156
Q

Translocation of Acetyl CoA via carnitine

A

Acetyl-CoA may also pass out through the mitochondrial membrane in the form of acetyl-carnitine. This requires the enzyme carnitine-acetyl transferase.

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157
Q

what are the enzymes used in Extra mitochondrial FA synthesis?

A
  1. Acetyl-CoA carboxylase
  2. fatty acid synthase complex (multi-enzyme complex)
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158
Q

Nature of Fatty acid synthase

A
  • This complex is a dimer (2 subunits).
  • Each monomer contains all 7 enzymes of FA synthase.
  • The acyl radical will combine acyl carrier protein (ACP).
  • ACP contains pantothenic acid (Vit B5) containing SH group.
  • In close proximity is another SH group of β-ketoacyl synthase
    (condensing enzyme) of other monomer.
  • The 2 monomers lie in head to tail configuration.
  • Since both SH group participate in the synthase activity, only the dimer is active.
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159
Q

what are the steps of extramitochondrial pathway of FA synthesis?

A
  1. Synthesis of malonyl-CoA (3C) by acetyl-CoA carboxylase
  2. Synthesis of palmitate by the fatty acid synthase complex
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160
Q

Synthesis of malonyl CoA

A

It is synthesized from acetyl-CoA in presence of ATP, biotin and bicarbonate as a source of CO2.

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161
Q

Synthesis of palmitate by the fatty acid synthetase complex

A

The first 3 steps involves 3 enzyme actions:
* 1st step is addition of an acetyl CoA to SH group at position 1
* 2nd step is addition of a malonyl CoA to SH group at position 2
* 3rd step is condensation of the acetyl CoA in position 1 with the malonyl CoA in position 2 with the release of one CO2

——–
Next 4 steps process involves 3 enzyme actions:
1. Reduction in the presence of NADPH+.
2. Dehydration release of one H2O.
3. Reduction in the presence of NADPH+.
4. Transfer from position 2 to 1.

——-
Now position 2 is free to accept a new malonyl CoA.

——-
This sequence of reactions is repeated six more Times by addition of a new malonyl CoA at position 2 each time until 16 carbon acyl radical (palmitic) is formed.

——-

Palmitic acid is released from the enzyme complex by the enzyme thioesterase (deacylase)

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162
Q

what is the rate limiting reaction in FA synthesis?

A

acetyl-CoA carboxylase step (i.e. synthesis of Malonyl CoA).

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163
Q

alloseteric regulation of FA synthesis

A

Acetyl-CoA carboxylase is an allosteric enzyme:
- activated by citrate
- inhibited by long chain FA.

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164
Q

hormonal regulation of fatty acid synthesis

A
  • Insulin activates acetyl-CoA carboxylase by dephosphorylation.
  • Glucagon and epinephrine inhibit acetyl-CoA carboxylase by increasing cAMP (phosphorylation).
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165
Q

what is the source of NADPH+H in FA synthesis?

A

1) Hexose Monophosphate Shunt (pentose shunt) (the chief source)

  • The tissues which possess an active HMP are specific for lipogenesis. Both metabolic pathways are found in the cytoplasm of the cell. So there is no membrane or permeability barrier for the transfer of NADPH+H/NADP.

2) Malic enzyme.

3) Cytoplasmic isocitrate dehydrogenase (of minor importance).

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166
Q

what are the fate of free palmitate?

A

Free palmitate must be activated to palmityl CoA before it can be used or proceeds via any other pathway as:

  1. Esterification with glycerol (to form TG) or with cholesterol (to form cholesterol esters)
  2. Chain elongation: For synthesis of longer chain F.A.
  3. Desaturation→Synthesis of unsaturated FA.
  4. Sphingosine formation: Palmityl CoA + amino acid serine
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167
Q

what is the source of glycerol-3-p used in FA synthesis?

A
  1. Glycerol-3-P is formed from glycerol by the enzyme glycerol-kinase in presence o ATP.
    - Glycerokinase enzyme is absent or very low in activity in muscle and adipose tissue.

————

  1. Alternative source is derived from intermediates of the glycolysis:
    - Glucose is oxidized to DHAP which is reduced to glycerol-3-P by the enzyme glycerol-3 phosphate dehydrogenase.
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168
Q

Biosynthesis of Triglycerides

A
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169
Q

what are the forms of lipids in human body?

A

The lipids in the body physiologically exist in two forms:

1- structural lipids.

2- stored lipids (Depot fats; adipose tissue) =The stored calories in the form of triglycerides.

170
Q

what do triglycerides of adipose tissue continually undergo?

A

The TG of adipose tissue are continually undergoing hydrolysis (Lipolysis) and re- esterification.

171
Q

what determines the amount of free fatty acids release from adipose tissue into blood?

A

The results of these two processes (Lipolysis & esterificattion) determines the amount of FFA released from adipose tissue into blood.

172
Q

when do Free fatty acids accumulate and diffuses into the plasma?

A

When the rate of lipolysis > the rate of re-esterification

173
Q

what regulates lipolysis & re-esterification?

A

Many of the nutritional, metabolic and hormonal factors

174
Q

what does hydrolysis of triacylglycerols (lypolysis) in adipose tissue occur under control of?

A

hormone-sensitive triacyl-glycerol lipase

175
Q

what are Adipolytic lipases?

A

Hormone sensitive triacylglycerol lipase: Key regulating enzyme.

The two non-hormone-sensitive lipases:
* Diacylglycerol lipase
* Monoacylglycerol lipase.

lipoprotein lipase: present in the capillary wall (that catalyses hydrolysis of the TG present in chylomicrons and VLDL).

176
Q

what are the forms of Hormone-sensitive triacylglycerol lipase?

A
  • An active form (lipase a) which is phosphorylated by protein kinase. (Protein kinase is cAMP dependent)
  • An inactive form (lipase b) which is dephosphorylated by phosphatase.
177
Q

what is the fate of fatty acids produced from lipolysis?

A
  • The bulk of free fatty acids formed by (lipolysis) can be reconverted in the tissue to acyl-CoA by Acyl-CoA synthase then re-esterified with Glycerol-3- P.
  • Some of hydrolyzed FA return to circulation being carried by albumin (FFA Pool).
178
Q

what is the fate of glycerol produced from fatty acids lipolysis?

A
  • Adipose tissue (and muscles) lacks Glycerol kinase enzyme, so the glycerol passes into the blood and is taken by the liver, kidney and other tissues which possess glycerokinase and to be utilized for gluconeogenesis.
179
Q

how does glucose affect Lipolysis?

A
  • On adequate nutritional intake, glucose utilization by adipose tissue is ↑ with ↑ Glycerol-3-P production.
  • So, re-esterification > lipolysis and↓ plasma FFA levels.
180
Q

how does diabetes, mellitus and starvation affect lipolysis?

A
  • In both conditions, ↓ glucose availability in the adipose tissue resulting in ↓ Glycerol-3-P.
  • So, re-esterification < Lipolysis and ↑ plasma FFA levels.
181
Q

what hormone increases the rate of esterification and decreases lipolysis?

A

(Insulin is the principal hormone)

  • Insulin with a diet rich in carbohydrates ↑ both the re-esterification of FAA and lipogenesis (with ↓ FFA release into blood). Insulin acts by:
    1. Increase transport of glucose into the fat cell.
    2. Stimulation of glycolysis (Glycerol-3-P)
    3. simulation of HMP shunt (NADPH+H+)
    4. Increase activity of: pyruvate dehydrogenase (↑ acetyl CoA), acetyl-CoA carboxylase (↑ FA synthesis), glycerol-phosphate acyl transferase (↑ TG synthesis).
  • Insulin ↓ lipolysis (↓ the release of FFA from adipose tissue) by inhibiting the activity of hormone- sensitive triglyceride lipase through ↓ cAMP ↓ release of FFA and glycerol.
182
Q

which hormones increase lipolysis?

A
  • Catecholamines (epinephrine and norepinephrine) are the principal hormones.
  • Glucagon, GH, Glucocorticoids, Most of them act by activating adenyl cyclase, thus ↑ cAMP to activate hormone-sensitive triacylglycerol lipase.
  • Glucocorticoids stimulate the synthesis of the triacylglycerol lipase enzyme.
183
Q

what are the pathways of fatty acid Oxidation?

A

Major Pathway: β-oxidation Energy Production

Minor Pathway: alpha & Omega oxidation

184
Q

what is the definition of beta oxidation of fatty acids?

A

major pathway for catabolism of fatty acids and in which two carbon fragments are successively removed from the carboxyl end of the fatty acyl CoA, producing acetyl CoA, NADH & FADH2

185
Q

what is the site of beta oxidation of fatty acids?

A
  • Mitochondria of many tissues (Mainly liver, kidney & heart)
  • Doesn’t occur in brain (FA cannot be taken up by brain or RBCs)
186
Q

what are the steps of beta oxidation of fatty acids?

A
  1. Fatty acid activation (In Cytoplasm)
  2. Transport of active FA from cytoplasm to mitochondria
187
Q

Transportation of active fatty acids from cytoplasm into mitochondria

A
188
Q

what are the sources of carnitine?

A

1- Carnitine can be obtained from the diet (meat products).

2- Carnitine can also be synthesized from the amino acids lysine and methionine by an enzymatic pathway found in the liver and kidney but not inskeletal or heart muscle

189
Q

what are the steps, enzymes and mechanism of beta oxidation of fatty acids?

A
190
Q

what regulates beta oxidation of fatty acids?

A
191
Q

Energy produced from beta oxidation of fatty acids (palmitic acid, for example)

A
192
Q

what regulates cAMP formation?

A

cAMP formation (by adenyl cyclase enzyme) is:

  • inhibited by insulin.
  • activated by adrenaline, noradrenaline, glucagon, ACTH, TSH, MSH.
193
Q

activation of fatty acids

A
194
Q

what is the definition of lipoproteins?

A

spherical, macromolecule complexes of lipids and specific protein called apo-protein (apo-lipoprotein)

195
Q

what are the functions of lipoproteins?

A

Lipid transport in the blood

  • Lipids are insoluble in water, Lipids bind to protein to make lipoproteins water-soluble to be transported in the blood). So, provide an efficient mechanism for transporting their lipid contents to and from the tissues.
196
Q

what is the general composition of plasma lipoproteins?

A
  • Lipoproteins are complex particles that have a central hydrophobic core of non-polar lipids, primarily cholesterol esters and triglycerides.
  • This hydrophobic core is surrounded by a hydrophilic membrane consisting of phospholipids, free cholesterol, and apolipoproteins.
197
Q

classification of lipoproteins

A

1) Chylomicrons
2) Very low density lipoproteins (VLDL)
3) low density lipoproteins (LDL)
4) High density lipoproteins (HDL)

198
Q

what is the site of synthesis of chylomicrons?

A

intestinal mucosa

199
Q

what is the composition of chylomicrons?

A
  • lipid core (non polar triglyceride 85% and cholesterol ester 3% )
  • surrounded by single layer of phospholipids 8% & cholesterol
  • Outer protein layer called apolipoprotein B-48 (1-2%)
200
Q

what are the functions of chylomicrons?

A

transport exogenous (dietary) triglycerides, cholesterol ester &
phospholipids from the intestine to peripheral tissues (liver, muscle, adipose tissue)

201
Q

steps of metabolism of chylomicrons

A
  • Synthesis of nascent chylomicrons
  • conversion of nascent chylomicrons to mature chylomicrons
  • Degradation of chylomicrons
  • Formation of chylomicron remnants
  • Fate of chylomicron remnants
202
Q

Synthesis of nascent chylomicrons

A
  • Nascent chylomicrons are formed in the intestinal mucosa and pass to lymphatic to then to general circulation through the thoracic duct.
203
Q

Conversion of nascent chylomicrons to mature chylomicrons

A
  • After entering the bloodstream, the chylomicron particles receive apo E (which is recognized by hepatic receptors) and C Apolipoproteins (apo C-II) from circulating HDL converted to mature CM
204
Q

Degradation of chylomicrons

A
  • Apo-CII activates lipoprotein lipase (LPL= clearing factor)
  • Lipoprotein lipase (LPL) (clearing factor) is an extracellular enzyme that is bound to the endothelial surface of capillary walls of most peripheral tissues (adipose tissue, cardiac and skeletal muscle).
  • LPL Hydrolyze triglyceride (TG) in the core of CM to free fatty acids and glycerol.
  • The fatty acids are stores (by the adipose) or used for energy (by the muscle)
  • Glycerol is used by the liver for example in lipid synthesis, glycolysis or gluconeogenesis.
205
Q

Formation of chylomicron remenants

A

As the of TG in the core is degraded by lipoprotein lipase,
a- the particle decreases in size and increase in density.
b- the C apoproteins (but not apo E) are returned to HDLs, the remaining particle, called chylomicron remnants

206
Q

Fate of chylomicron remenants

A
  • CM remnants is rapidly removed from the circulation by the liver via Lipoprotein receptors that recognize apo E.
  • They interact with receptors on liver cells and are taken by endocytosis, then catabolized within the hepatic lysosomes releasing (amino acids, fatty acids, cholesterol) into the cytosol and reutilized by the hepatic cells.
207
Q

what converts nascent chylomicrons into mature chylomicrons?

A

apo E (which is recognized by hepatic receptors) and C Apolipoproteins (apo C-II) from circulating HDL converted to mature CM

208
Q

How do nascent chylomicrons reach the general circulation?

A

through the thoracic duct

209
Q

what activates LPL?

A

Apo-CII

210
Q

what is LPL?

A

(clearing factor) is an extracellular enzyme that is bound to the endothelial surface of capillary walls of most peripheral tissues (adipose tissue, cardiac and skeletal muscle).

211
Q

what is the action of LPL?

A

Hydrolyze triglyceride (TG) in the core of CM to free fatty acids and glycerol.

212
Q

what is the fate of products of LPL action?

A
  • The fatty acids are stores (by the adipose) or used for energy (by the muscle
  • Glycerol is used by the liver for example in lipid synthesis, glycolysis or gluconeogenesis.
213
Q

what is the site of Synthesis of VLDL?

A

liver

214
Q

what is the composition of VLDL?

A
  • triglycerides 55%
  • phospholipids 20%
  • cholesterol ester 15%
  • cholesterol 8%,
  • protein 7-10% mainly B 100
215
Q

what is the function of VLDL?

A

Transport triglycerides from liver to extrahepatic tissues

216
Q

metabolism of VLDL

A
  • VLDLs are secreted directly into the blood by the liver as nascent VLDL particles containing Apolipoprotein B-100.
  • They obtain apo CII and apo E from circulating HDL and become mature VLDL, apo CII is required for activation of lipoprotein lipase.
  • AS VLDLs pass through the circulation TG is degraded by lipoprotein lipase, causing the VLDL to decrease in size and become denser.
  • Surface components including apo CII lipoproteins are returned to HDL → forming intermediate-density lipoprotein (IDL) or VLDL remnant .
  • Then mention the fate of IDL
217
Q

what is the fate of IDL?

A
  • A small amount of IDL is taken up by liver through receptor-mediated endocytosis that uses apo E as the ligand.

___________________

  • Most of IDL converted to LDL by
    1- losing their apo-E
    2- Transferring cholesterol ester from HDL to IDL in an exchange with phospholipids or TG [this exchange is carried out by cholesterol ester transfer protein (CETP) (apo D) a component of HDL).
218
Q

what is the source of LDL?

A

VLDL

219
Q

what is the composition of LDL?

A
  • 13% triglycerides
  • 28% phospholipids
  • 48% cholesterol ester
  • 10% free cholesterol
  • 20% protein mainly apo B100
220
Q

what is the function of LDL?

A

Carry cholesterol from liver to extrahepatic tissue

221
Q

metabolism of LDL

A
  • LDL is not synthesized / or secreted by the liver or intestine. It is formed principally by degradation of circulating VLDL which initially forms IDL.
  • Most IDL particles change into LDL particles, by losing their apo-E also triacylglycerol is transferred to HDL in exchange with cholesterol esters, this is catalyzed by cholesterol ester transfer protein (apo D).
  • The most core lipid in LDL is cholesterol ester and ApoB100 is the only apolipoprotein on the surface.
  • This makes LDL richer in cholesterol esters and free cholesterol and poorer in TG.
222
Q

what is the fate of LDL?

A
  • LDL bind to specific apo-B-100 receptors in both extrahepatic tissues (30%) and liver (70%) where they are endocytosed and their contents are metabolized.
  • LDLs are an important source of cholesterol to extrahepatic tissues.
223
Q

what is the name of LDL receptors?

A

LDL receptors are named apo B-100 / apo E receptors because of their ability to recognize particles containing both apo B-100 and E.

224
Q

what do High levels of LDL-cholesterol Cause?

A
  • increase the risk of atherosclerosis
  • Atherosclerosis is the buildup of LDL bad cholesterol which causes hardening of the arteries and blockage to flow.
225
Q

what is the source of HDL?

A

synthesized mainly in liver & to lesser extent in the intestine

226
Q

what is the composition of HDL?

A
  • Triglycerides 3%.
  • Free cholesterol 5%.
  • Cholesterol esters 15%.
  • Phospholipids 25%
  • Proteins 50% mainly apo A
227
Q

what are the functions of HDL?

A
  1. Reservoir of apolipoproteins
  2. uptake of unesterified cholesterol
  3. Estrifications of cholesterol
  4. Reverse cholesterol transport
228
Q

HDL as a Reservoir of apolipoproteins

A
  • HDL particles serve as a circulating reservoir of apo C II (the apoprotein that is transferred to VLDL & chylomicron & is activator of lipoprotein lipase) & and apo E (apolipoprotein requiring for the receptor mediated endocytosis of IDLs and chylomicron remnants)
229
Q

HDL uptake of unesterified cholesterol

A

Nascent HDL are disk-shaped particles containing primarily phospholipid (largely phosphatidylcholine) and apolipoproteins A, C, and E. They take up cholesterol from peripheral tissues and return it to the liver as cholesteryl esters this phenomenon is termed (reverse cholesterol transport)

230
Q

what is reverse cholesterol transport?

A

They take up cholesterol from peripheral tissues and return it to the liver as cholesteryl esters

231
Q

what mediates the transfer of free cholesterol from plasma membrane to HDL?

A

by a membrane transporter designated ATP binding cassette transporter (ABCA 1), also transfer phospholipids along with free cholesterol to nascent HDL

232
Q

Estrifications of cholesterol by HDL

A
  • When cholesterol is taken up by HDL it is immediately esterified by plasma enzyme LCAT which is synthesized by liver.
  • LCAT binds to nascent HDL and is activated by apo A1.
  • LCAT transfers the FA from carbon 2 of lecithin to cholesterol this produces a hydrophobic CE which is sequestred in the core of the HDL & lysophosphatidylcholine which bind to albumin
  • As the nascent HDL accumulates cholesterol esters it first becomes classified as HDL3 and further addition of CE to HDL3 produce HDL2.
  • CE generated transferred to VLDL & IDL by CETP associated with HDL particles.
233
Q

Reverse cholesterol transport by HDL

A

The selective transfer of cholesterol from peripheral cells to HDL, and from HDL to the liver for bile acid synthesis or disposal via the bile, and to steroidogenic cells for hormone synthesis.
This is the basis for the inverse relationship seen between plasma HDL concentration and atherosclerosis, and for HDL’s designation as the “good” cholesterol carrier

234
Q

Degradation of HDL

A

Takes place in the liver by:

  1. selection uptake of CE mediated by called scavenger receptor B1 (SR-B1).
  2. cell surface hepatic lipase that hydrolyses TG of HDL particles.
  3. The apoA1 from the degradation of HDL is recycled for new HDL formation.
235
Q

what is amino acids pool?

A

The amount of free amino acids distributed throughout the body

Plasma level: 4-8 mg / dl

236
Q

what is the source of amino acid pool?

A
  1. Dietary protein.
  2. Breakdown of tissue proteins.
  3. Biosynthesis of nonessential amino acids.
237
Q

what is the fate of amino acid pool?

A
238
Q

what are the catabolic pathways of amino acids?

A
  • Transamination
  • Deamination
  • Decarboxylation Reaction (Amines Formation)
239
Q

what is the definition of transamination?

A

Transamination means transfer of amino group from α-amino acid to α-keto acid with formation of a new α-amino acid and a new α-keto acid

240
Q

what is the site of transamination?

A

The liver is the main site for transamination.

241
Q

what are the amino acids that can be transaminated?

A

All amino acids can be transaminated except lysine, threonine, proline, hydroxyproline

242
Q

what is the coenzyme involved in transamination?

A

pyridoxal phosphate

243
Q

what are the characteristics of transamination reactions?

A

reversible and catalyzed by transaminases.

244
Q

what are examples of transaminases?

A
  • Alanine transaminase (ALT) or glutamic pyruvic transaminase (GPT)
  • Aspartate transaminase(AST) or glutamic oxaloacetic transaminase
245
Q

Compare between ALT (SGPT) & AST (SGOT) in terms of:-
- Reaction
- Site
- Clinical Significance

A
246
Q

what is the clinical significance of transaminases?

A
  • Transaminases are intracellular enzymes, Their levels in blood plasma are low under normal conditions.
  • ALT (GPT) is present mainly in the cytoplasm of liver cells.
  • AST (GOT) is present in both cytoplasm and mitochondria in liver, heart, and skeletal muscles.
    _________________________
  • Any damage to these organs will increase the level of transaminases in blood
    1. In liver diseases, there is an increase in both serums ALT (SGPT) and AST (SGOT) levels.
    2. In acute liver diseases, e.g. acute viral hepatitis, the increase is more in SGPT.
    3. In chronic liver diseases, e.g. liver cirrhosis the increase is more in SGOT.
    4. In heart diseases, e.g. myocardial infarction, there is an increase in SGOT only.
247
Q

what is the definition of deamination?

A

removal of amino group from α-amino acid in the form of ammonia with formation of α-keto acid.

248
Q

what is the site of the deamination?

A

liver and kidney are the main sites for deamination.

249
Q

what are the types of deamination?

A

Oxidative & Non-oxidative

250
Q

compare between L-aa oxidase, D- aa oxidase & Glutamate Dehydrogenase in terms of:-

  • Substrate
  • Activity
  • Type
  • Coenzyme
  • Site
  • Reversibility
A
251
Q

what is the definition of decarboxylation reaction of Amino acids (Amine formation)?

A

removal of the carboxylic group in the form of CO2 from amino acid with formation of corresponding amines.

252
Q

which enzyme catalyzes decarboxylation reaction of Amino acids (Amine formation)?

A

decarboxylase enzyme.

253
Q

what is the coenzyme for decarboxylation reaction of Amino acids (Amine formation)?

A

pyridoxal phosphate

254
Q

what are examples of amines and their corrosponding amino acids? then mention their biological importance.

A
255
Q

what is the blood level of Ammonia?

A

10-60 ug/dl

256
Q

is ammonia toxic?

A

Ammonia is toxic to the central nervous system and its accumulation in the body is fatal.

257
Q

what does liver convert ammonia into?

A
  • The liver converts ammonia to urea by urea cycle (Kerbs Hensleit cycle) , which is less toxic, water soluble and easily excreted in urine.
258
Q

deamination of AA, Purines & Pyrimidines Catabolism, Action of bacteria

what are the sources of Ammonia?

A

1- Deamination of amino acid with formation of α-keto acids and ammonia.

————

2- Transamination of most amino acids with α-ketoglutaric acid to form glutamic acid, which in turn is deaminated by glutamate dehydrogenase to form α-ketoglutarate and ammonia.

————

3-Glutamine in the kidney by glutaminase enzyme gives glutamic acid and ammonia, which is used by kidney to regulate the acid base balance.

———–

4- Ammonia produced by the action of intestinal bacteria on the non-absorbed dietary amino acids.

———–

5- Ammonia is released from monoamines (e.g. epinephrine, norepinephrine, and dopamine) by the action of monoamine oxidase enzyme.

————-

6- Ammonia is released during purine & pyrimindine catabolism.

259
Q

Synthesis of glutamine, glutamic acid, Synthesis of AA, Catabolism

what is the fate of ammonia?

A

1- Biosynthesis of glutamic acid from ammonia and α-ketoglutaric acid by the action of glutamate dehydrogenase enzyme.
———–

2- Biosynthesis of non-essential amino acids through transdeamination reaction (transamination with ketoglutaric acid by transaminases followed by deamination of the produced glutamic acid by glutamate dehydrogenase enzyme).
———–
3- Biosynthesis of glutamine by glutamine synthetase enzyme.
———-
4- Small amounts of ammonia are excreted in urine in the form of ammonium ions.
————-
5- Urea biosynthesis.

260
Q

what is the site of the steps of urea cycle?

A

The first 2 steps occur in the mitochondria & the last 3 steps occur in cytoplasm.

261
Q

what is the amount of ATP used in urea Biosynthesis?

A

It utilizes 3 ATP and 4 high energy bonds.

262
Q

what is the site of urea biosynthesis?

A

Liver

263
Q

what are the steps of urea biosynthesis?

A
  1. Biosynthesis of carbamyl phosphate
  2. Formation of citrulline
  3. Formation of argininosuccinate
  4. Cleavage of argininosuccinate
  5. Cleavage of arginine
264
Q

Biosynthesis of carbamyl phosphate

A
  • This step occurs in mitochondria and needs CO2, ammonia and phosphate and energy.
  • CO2 is a product of citric acid cycle.
  • Ammonia is derived from glutamate by deamination.
  • The phosphate and energy are derived from ATP.
  • It is catalyzed by carbamoyl phosphate synthetase-I.
265
Q

Formation of citrulline

A
  • This step occurs in mitochondria.
  • It is catalyzed by ornithine transcarbamylase.
266
Q

Formation of argininosuccinate

A
  • This step occurs in cytoplasm.
  • It is catalyzed by argininosuccinate synthetase.
  • It utilizes one ATP and 2 high energy bonds
267
Q

Cleavage of argininosuccinate

A
  • It is catalyzed by argininosuccinase enzyme.
  • Argininosuccinate is cleaved into arginine and fumarate.
  • Fumarate produced is used to regenerate aspartic acid again.
268
Q

Cleavage of arginine

A
  • It is catalyzed by arginase enzyme.
  • Arginine is cleaved to urea and ornithine.
269
Q

what are the types of regulation of urea cycle?

A
  • Short-term regulation
  • Long-term regulation
270
Q

what is the Key enzyme in urea cycle?

A

carbamoyl phosphate synthetase-I.

271
Q

what is an allosteric activator of Urea cylce? And how is it synthesized?

A
  • N-acetyl glutamate is allosteric activator of carbamoyl phosphate synthetase-I
  • N-acetyl glutamate is synthesized from acetyl CoA and glutamate by N-acetyl glutamate synthetase enzyme, which is allosterically activated by arginine.
272
Q

Long-term regulation of urea cycle

A
  • Enzymes of the urea cycle are controlled at the gene level with long-term changes in the quanitity of dietary protein.
  • Long-term increase in the quantity of dietary proteins leads to a significant increase in the concentration of the enzymes of urea cycle
273
Q

what are the causes of Hyperammonemia?

A

Acquired hyperammonemia: Liver diseases

Inherited hyperammonemia: Genetic deficiencies of any of the 5 enzymes of urea cycle

274
Q

what is the importance of glycine?

A

1) Detoxication of Benzoic acid.
2) Conjugation with bile acids to form bile salts .

3) Synthesis of :
- Purine bases: C4, C5, N7.
- Heme.
- Glucose.
- Glutathione (detoxify H2O2 by converting it to 2 molecules of H2o).
- Creatine and creatinine.
- Serine.

275
Q

what is the normal creatinine level in urine?

A
  • 1 gm/day in female.
  • 1.5 gm/day in males.
276
Q

what are the amino acids that form creatine?

A

Glycine, Arginine and methionine (GAM).

277
Q

what is the difference between creatine and creatinine?

A

creatinine is the excretory product in urine

278
Q

what are the types of Alanine?

A

α-Alanine & β-Alanine

279
Q

what is the importance of α-Alanine?

A

Synthesis of:
- Protein.
- Pyruvic acid.
- glucose.

280
Q

what is the importance of β-Alanine?

A

1) Forms di-peptides with histidine as anserine , carnosine in brain & Skeletal ms which used for :
- Activate myosin ATPase enzyme.
- Have antioxidant activity.

2) Formation of pantothenic acid & COASH

281
Q

what is the importance of serine?

A
  1. Phosphoprotein.
  2. Formation of ethanolamine.
  3. Biosynthesis of choline.
  4. Biosynthesis of sphingosine.
  5. Formation of glycine & cysteine.
  6. Glucogenic.
282
Q

what is the importance of cysteine?

A
  1. Sulphur containing Hormones as insulin
  2. Some enzymes
  3. Taurine which enters in formation of Bile salts
  4. Detoxication reactions
  5. Glutathione (y-glutamyl-cysteinylglycine).
  6. COASH.
  7. Glucogenic.
283
Q

what is the importance of Phenylalanine?

A

1) Protein structure
2) Synthesis of glucose
3) Synthesis of ketone bodies
4) Biosynthesis of tyrosine

284
Q

what is the importance of Tyrosine?

A

1) Protein structure
2) Synthesis of glucose
3) Synthesis of ketone bodies
4) Biosynthesis of melanin pigment
5) Biosynthesis of thyroid hormones
6) Biosynthesis of catecholamines

285
Q

what is the importance of Tryptophan?

A

1) Protein structure
2) Synthesis of glucose
3) Synthesis of ketone bodies
4) Biosynthesis of melatonin → antioxidants.
5) Biosynthesis of serotonin → neurotransmitter.
6) Biosynthesis of Niacin (vitamin B3)

286
Q

what are aromatic amino acids?

A
  • Phenylalanine
  • Tyrosine
  • Tryptophan
287
Q

what is the cause of Phenylketonuria?

A
  • Congenital deficiency of phenylalanine hydroxylase enzyme.
  • Phenylalanine is converted to phenyl-pyruvic, phenyl- lactic, and phenyl-acetic.
288
Q

what are the symptoms of Phenylketonuria?

A
  • Mental retardation.
  • Neyrologic manifestations.
  • Mousy odour of urine.
289
Q

prevention of Phenylketonuria

A

Diet poor in phenylalanine and rich in tyrosine.

290
Q

what is the cause of Albinism?

A

Inherited deficiency of tyrosinase enzyme in melanocytes (no synthesis of melanin pigment).

291
Q

what are the symptoms of albinism?

A
  • Skin, and hair are whitish.
  • Iris is colorless, but, appears red due to presence of blood vessels.
292
Q

what are the causes of Hartnup disease?

A
  • It is a hereditary disease in tryptophan metabolism, where there is an impairment in intestinal absorption, renal tubular reabsorption of tryptophan .
293
Q

what are the symptoms of Hartnup disease?

A

Defect in niacin (vit B) leads to pellagra (diarrhea, dermatitis, dementia).

294
Q

what are acidic amino acids?

A

Glutamic & Aspartic acid

295
Q

what is the importance of Glutamic acid?

A
  • Glutamine formation (remove excess NH3 in brain).
  • Glutathione formation.
  • GABA formation (inhibitory neurotransmitter).
  • Formation of N-acetyl glutamic (allosteric activator of carbamyl phosphate synthetase 1 in urea cycle)
  • Folic acid (vit B10) synthesis.
  • Proline, ornithine formation.
  • Glucogenic.
296
Q

what is the importance of aspartic acid?

A
  • Sources of N1 of purine.
  • Sources of N1, C4,5,6 of pyrimidine.
  • Asparagine formation.
  • B-alanine formation.
  • Urea formation.
  • Glucogenic.
297
Q

what are basic amino acids?

A
  • Histidine, Arginine & Lysine
298
Q

what is the importance of histidine?

A
  1. Histamine formation by decarboxylation.
    - VD.
    - Neurotransmitter
  2. Histidine with β-alanine form dipeptide carnosine & anserine in ms.
  3. Ergothionine (antioxidant)
  4. Glucogenic.
299
Q

what is the importance of arginine?

A
  • Urea formation.
  • Creatine, creatinine formation.
  • Nitric oxide (VD and ↓ BP and neurotransmitter) by nitrous oxide synthetase.
300
Q

what is the importance of lysine?

A
  • Combine with biotin to form biocytin which act as co-enzyme for carboxylase .
  • CO2 fixation
  • Collagen synthesis
  • Glucogenic and ketogenic
301
Q

what are examples of sulfur containing amino acids?

A

Cysteine & Methionine

302
Q

what is the importance of methionine?

A
  • Protein synthesis.
  • Convert to active form which is S-adenosyl methionine (SAM) which act as methyl donor.
303
Q

what are the disorders of branched amino acids?

A

Maple syrup urine disease

304
Q

what is the cause of maple syrup urine disease?

A
  • Inborn error of branched chain AA metabolism.
  • Deficiency in α keto acid decarboxylase with accumulation of
    valine, leucine and isoleucine in blood and increase in urine.
305
Q

manifestations of maple syrup urine disease

A
  • Characteristic odor of urine (maple syrup or burnt sugar).
  • Extensive brain damage.
  • Without treatment, death with in one year.
306
Q

Reaction for acidic amino acids metabolism

A
307
Q

Reactions for basic amino acids metabolism

A
308
Q

what are branched amino acids?

A
  • Valine –> Glucogenic
  • Leucine –> Ketogenic
  • Isoleucine –> Mixed
309
Q

what are nucleic acids?

A

polymers of nucleotides.

310
Q

what are the types of nucleic acids?

A

There are two types of nucleic acids:

(a) Ribonucleic acid (RNA)
(b) Deoxyribonucleic acid (DNA)

311
Q

what is the function of nucleic acids?

A

Storage and expression of genetic information.

312
Q

what is the difference between Nucleotide, Nucleoside?

A
313
Q

what is the definition of nitrogenous bases?

A

planar, aromatic, heterocyclic molecules that are structural derivatives of Purine or Pyrimidine

314
Q

what are the types of nitrogenous bases?

A
  • The most common Purine ( Adenine and Guanine)
  • The most common Pyrimidine (Cytosine, Thymine (DNA) & Uracil (RNA))
315
Q

what contributes in the formation of the atoms of purine ring?

A
316
Q

what is purine ring built up on during de novo synthesis of purines?

A

ribose-5-phosphate molecule

317
Q

what is the number of steps of de novo synthesis of purines?

A

10 steps

318
Q

what is a Enzyme which catalyzes de novo synthesis of purines?

A

multienzyme complex in eukaryotic cells.

319
Q

what are the steps of de novo synthesis of purines?

A
  • Synthesis of 5’ phospho-ribosyl-1- pyrophosphate (PRPP) (Step 0 “Preparatory Step”)
  • Synthesis of 5’ phospho-ribosylamine: by PRPP glutamyl amido-transferase (Step 1)
  • Synthesis of Inosine mono-phosphate (IMP) (Steps 2-10)
320
Q

Preliminary or preparatory step of de novo synthesis of purines

A
  • Ribose-5-phosphate is the donor of PRPP for de novo synthesis. PRPP is also used for the salvage pathway.
  • The synthesis of PRPP is not considered as a step in the de novo synthesis of purine nucleotides; it is called a preliminary or preparatory step.
  • Ribose-5-P is derived from pentose shunt.
321
Q

step 1 in de novo synthesis of purines

A

Synthesis of 5’ phospho-ribosylamine: by PRPP glutamyl amido-transferase (Step 1)

322
Q

steps 2-10 in de novo synthesis of purines

A
  • 5’phosphoribosylamine is converted to IMP by sequence of 9 linear reactions
  • energetically expensive process
  • IMP is parent purine nucleotides
  • Conversion of IMP to AMP (adenosine mono- phosphate), and GMP (guanosine mono-phosphate)
323
Q

what is the significance of salvage pathway of purine synthesis?

A
  • it ensures the recycling of purines resulting from degradation of nucleotides
  • It is of special importance in tissues like RBCs and brain. Where the de novo pathway is not operating.
  • economizes intracellular energy expenditure
324
Q

what is the starting material of salvage pathway in purine synthesis?

A

PRPP, it is also a substrate for de novo synthesis, hence these two pathways are closely interrelated

325
Q

mechanism of salvage pathway in purine synthesis

A

Phosphoribosylation of purine bases:
- The free purines are salvaged by two different enzymes; adenine phospho ribosyl transferase (APRTase) and hypoxanthine guanine phosphoribosyl transferase (HGPRTase) by addition of PRPP.

Direct Phosphorylation of purine nucleosides

326
Q

purine catabolism

A
327
Q

what is in the product of purine catabolism and what is its levels in blood?

A

Uric acid

Normal blood level: in man (4-7 mg/dl), In women (3-6mg/dl)

328
Q

synthesis of the deoxyribonucleotides

A
329
Q

what is the definition of hyperuricemia?

A

serum uric acid concentration exceeding 7 mg/dl in male and 6 mg/dl in female.

330
Q

what are the causes of hyperuricemia?

A
331
Q

what is the clinical picture of hyperuricemia?

A

Gout

332
Q

what is the definition of hypouricemia?

A

Serum uric acid is less than 2mg/dl

333
Q

what are the causes of Hypouricemia?

A

Xanthine Oxidase deficiency: Increased execretion of xanthine and hypoxanthine

334
Q

compare between Adenosine deaminase deficiency & Nucleoside Phosphorylase deficiency in terms of:

  • Effect
  • Leads to
A
335
Q

what is the site of gout?

A

Mono articular, usually affecting the first meta-tarsophalengeal joint of the big toe, in male mainly

336
Q

pathophysiology of gout

A
337
Q

what is the cause of Lesch Nehan Syndrome

A

Defective HGPRT

  • in this condition, purine bases cannot be salvaged.
  • Instead, they are degraded, forming excessive amounts of uric acid leading to gout.
338
Q

what is the clinical picture of Lesch Nehan Syndrome?

A
  • developmental delays and intellectual disabilities
  • they are also prone to chewing of their fingers and performing other acts of self-mutilation
339
Q

what are the sources of carbon and nitrogen atoms in pyrimidine ring?

A
  • N1, C4, C5 & C6…… Aspartate
  • C2…… Co2
  • N3….. Amide group of glutamine
340
Q

what are the two pathways of pyrimidine synthesis?

A
  • De novo synthesis of pyrimidine nucleotides
  • Salvage pathway of pyrimidine nucleotides
341
Q

which is simpler, purine or pyrimidine synthesis?

A

pyrimidine

342
Q

what is the difference between purine and pyrimidine synthesis?

A
  • pyrimidines are synthesized as bases and ribose is added later on
343
Q

what are the steps of pyrimidine synthesis?

A
344
Q

salvage pathway of pyrimidine nucleotides

A
345
Q

degradation of pyrimidine nucleotide

A
  • The pyrimidine ring can be completely degraded in humans.
  • The products include: NH3, CO2, β-alanine, and β-aminoisobutyrate.
  • Both β -alanine, and β -aminoisobutyrate can be further converted into acetyl-CoA and succinyl-CoA, respectively, or are excreted in the urine.
346
Q

compare between CPS-I & CPS-II in terms of:

  • Intracellular location
  • Tissue Location
  • Function
  • Activation
  • Source of nitrogen
A
347
Q

what are pyrimidine related disorders?

A
  • Orotic aciduria
  • Deficiency of Urea cycle enzyme
348
Q

what are the types of ortic aciduria?

A

Type I & Type II

349
Q

what is the cause of type I Ortic aciduria?

A
  • Deficiency of both Orotate phospho-ribosyl transferase (OPRT) and orotidylate decarboxylase
  • orotate and OMP cannot be converted to UMP, CMP, TMP —-> Orotate & OMP accumlate —–> Inhibition of DNA and RNA synthesis
350
Q

what is the cause of Type II Ortic aciduria?

A
  • Deficiency of only orotidylate decarboxylase
  • OMP cannot be converted into UMP —-> inhibition of DNA / RNA synthesis
351
Q

what are the symptoms and signs of ortic aciduria?

A
  • Patients typically present with excessive orotic acid in the urine,
  • Failure to thrive, developmental delay
  • Megaloblastic anemia which cannot be cured by administration of vitamin B12 or folic acid
352
Q

what results from deficiency of urea cycle enzyme?

A
  • deficiency of ornithine trans carbamoylase
  • Carbamoyl-phosphate cannot enter urea cycle
  • Exits into cytosol & simulates pyrimidine synthesis
  • Leads to increased execretion of precursors of pyrimidines like orotic acid, uracil & orotidine
353
Q

what are the clinical disorders of Lipoproteins Dislipoprotenemias?

A

A. Hyper-lipoprofeinemia.
B. Hypo-lipoprofeinaemias.

354
Q

what is the definition of hyperlipidemias?

A

Group of disorders characterized by increased plasma lipoproteins.

355
Q

classification of hyperlipidemias

A

According to Fredrickson :

1- Type 1: Familial lipoprotein lipase deficiency

2- Type Il: familial hyper-cholesterolaemia (FHC)

3- Type III: Familial Dys-Beta lipoproteinemias.

4-Type IV: Hyper-pre-beta-lipoprotenemia

5- Type V: combined hyper-lipidemia

356
Q

what is the other name of Type I hyperlipidemia?

A

Familial lipoprotein lipase deficiency

357
Q

what is the other name of Type II hyperlipidemia?

A

Familial hyper-cholesterolacmia (FHC)

358
Q

what is the other name of Type III hyperlipidemia?

A

Familial Dys-Beta lipoproteinaemias = Broad Beta disease = Remnant removal disease

359
Q

what is the other name of Type IV hyperlipidemia?

A

Hyper-pre-beta-lipoproteinemia

360
Q

what is the other name of Type V hyperlipidemia?

A

Combined hyper-lipidaemia

361
Q

what are the characteristics of type I hyperlipidemia?

A
  • Inc. TG & chylomicron.
  • Inc. VLDL (pre-B lipoproteins) so inc. carbohydrate intake.
  • Dec. HDL & LDL.
362
Q

what are the characteristics of type II hyperlipidemia?

A
  • Hyper B lipoproteinaemia (LDL inc.)
  • inc total cholesterol.
363
Q

what are the causes of Type II hyperlipidemia?

A

a. Familial type is due to defect in LDL receptors in liver &
other tissues.

b. Acquired type occur in hypothyroidism.
- The thyroid hormone, T3 has a positive effect on the binding of LDL to its receptor.

364
Q

what are the characteristics of type III hyperlipidemia?

A
  • Inc remnants of VLDL (IDL) & chylomicron.
  • Hyper-cholesterolemia and Hyper-triglycerodemia
365
Q

what are the causes of Type III hyperlipidemia?

A
  • Familial type is caused by defective apo E necessary for uptake and metabolism of VLDL and chylomicron remenants by the liver.
366
Q

what are the characteristics of type IV hyperlipidemia?

A
  • inc plasma VLDL and TGs and some increase in plasma cholesterol.
367
Q

what are the causes of Type IV hyperlipidemia?

A
  • Familial type: due to inc formation of TGs from carbohydrates.
  • Acquired type: occurs in severe type II diabetes mellitus, obesity and alcoholism.
368
Q

what are the characteristics of type V hyperlipidemia?

A
  • Inc chylomicrons & VLDL
  • Inc TG and cholesterol
  • Usually associated with obesity.
369
Q

what are the causes of Type V hyperlipidemia?

A

The cause of disease in unknown but may be due to increase formation of аро В.

370
Q

what is Type V hyper lipidemia associated with?

A
  • Usually associated with obesity.
371
Q

classification of hypolipoproteinemia

A
  • Abeta lipoproteinaemia
  • Hypo-Beta Lipoproteinemia
  • Familial alpha lipoprotein deficiency (Tangiers disease)
  • Familial LCAT deficiency
372
Q

what is the cause of Abetalipoprotenemia?

A
  • caused by failure of the liver and intestine to synthesis apo-B
373
Q

what is the effect of Abetalipoprotenemia?

A
  • Absences of chylomicron, VLDL and LDL from blood
  • The intestine fails to absorb TGs (fatty diarrhea).
  • The liver fail to mobilize fats to blood leading to fatty liver.
374
Q

what is the cause of Hypo-beta-lipoprotenemia?

A
  • Caused by dec. formation of apo-Bioo by liver.
375
Q

what is the effect of Hypo-beta-lipoprotenemia?

A

decreased formation of VLDL and LDL.

376
Q

what is the cause of familial alpha Lipoprotein deficiency (Tangiers disease)?

A
  • Absence of ATP-binding cassette transporter
  • Reduction in apo-A
377
Q

what is the effect of familial alpha Lipoprotein deficiency (Tangiers disease)?

A
  • deficiency of a lipoprotein (HDL J.
  • Leading to accumulation of cholesterol esters in different tissues.
378
Q

what is the cause of Familial LCAT deficiency?

A
  • Abscent of phosphatidyl choline cholesterol acyl transferase (PCAT) or LCAT.
379
Q

what is the effect of Familial LCAT deficiency?

A
  • marked decrease in HDL.
380
Q

correlation between carbohydrate and lipid metabolism

A

Glucose to lipid:
Through:
- Acetyl CoA
- DHAP
- NADPH

Lipid to glucose:
Through:
- Glycerol
- Fatty acids

381
Q

Carbohydrate conversion to lipid

A

Carbohydrate in excess is converted to triacylglycerol in both adipose tissue and liver

382
Q

Acetyl CoA to lipid

A
  • Glucose by glycolysis is converted to pyruvic acid, then pyruvic by oxidative decarboxylation is converted into acetyle COA.
  • Acetyl COA can be used in cholesterol and triglycerides synthesis.
383
Q

DHAP to lipid

A
  • Glucose by glycolysis is converted into DHAP then DHAP is converted into glycerol 3 phosphate.
  • Glycerol-3-p (active glycerol) used in tri-acyl-glycerol biosynthesis.
384
Q

NADPH to lipid

A
  • NADPH originated from HMP pathway can be used for fatty acid biosynthesis.
385
Q

Glycerol to glucose

A

Can be phosphorylated to glycerol-3-phosphate then converted to dihydroxyacetone phosphate, which continues through glycolysis.

386
Q

Fatty acids to glucose

A
  • Beta-oxidation will form acetyl CoA that proceeds into the citric acid cycle.
  • The fatty acids with an odd number of carbon atoms yield propionyl COA as the product of the final cycle of beta oxidation and this can be a substrate for gluconeogenesis (relatively rare).
387
Q

correlation between carbohydrates and proteins

A

Protein to glucose:
Through:
- Glucogenic amino acids
- Mixed amino acids

388
Q

what happens to excess amino acids by deamination?

A
  • Excess amino acids by deamination will form alpha keto acids and ammonia:

a) the liver synthesizes urea from two ammonia molecules and a carbon dioxide molecule.

b) Alpha keto acid is called the carbon skeleton and can be re-used in biosynthesis of non-essential amino acids.

389
Q

what forms urea?

A
  • The liver synthesizes urea from two ammonia molecules and a carbon dioxide molecule.
390
Q

what are pure glucogenic amino acids?

A

tryptophan, phenylalanine, tyrosine, isoleucine, and threonine.

391
Q

what are glucogenic and ketogenic (Mixed) Amino acids?

A

Glycine, serine, aspartic acid, glutamic acid, glutamine, valine, methionine, histidine, and arginine

392
Q

correlation between lipids and proteins

A

protein to Lipid:
Through:
- Ketogenic amino acids

393
Q

what does metabolism serve for?

A
  1. Produce energy.
  2. Produce substance that are the building block of body.
  3. Produce glucose.
394
Q

what are the levels at which metabolism is related?

A
  1. The availability of substrates.
  2. Regulation through the action of allosteric enzymes, which increase or decrease the activity under the influence of effector molecules.
  3. Hormonal regulation.
  4. Regulation at DNA level: the concentration of the enzyme is changed by regulation at the level of synthesis of the enzyme.
395
Q

What is metabolism classified into?

A
  • Fed or anabolic state
  • Fasting or catabolic state
396
Q

compare between Fed or anabolic state & fasting or catabolic state

A
397
Q

Glucogenic amino acids into glucose

A

Amino acids which give Pyruvic acid (which gives glucose) or one of the intermediates of the Kreb’s cycle are Glucogenic

398
Q

Mixed amino acids to glucose

A
  • Amino acids which give Acetyl CoA and Pyruvic acid or one of the intermediates of Kreb’s cycle are both Glucogenic and Ketogenic
399
Q

mechanism by which pyruvate forms glucose

A

Pyruvate can be carboxylated to oxaloacetate, which is the primary substrate for gluconeogenesis, and other intermediates of the cycle.

400
Q

State of CHO in Liver in Fasting state

A
  1. ↑ Increased glycogen degradation (glycogenolysis):
    - By activation of glycogen phosphoreylase and inhibition of glycogen synthase

————-

  1. ↑ gluconeogenesis by activation of its key enzymes:
    - Fructose 1,6 bisphosphatase
    - Pyruvate carboxylase.
401
Q

State of CHO in muscles in Fasting state

A
  1. ↑glycogenolysis
    - Muscles can’t form glucose due to lack the enzyme glucose-6- phosphatase.
  2. ↓ Glucose uptake by the muscles
    - leads to decrease glucose metabolism in muscles
402
Q

State of CHO in adipose tissue in Fasting state

A

↓ Glucose uptake by the adipocytes
- leads to decrease glucose metabolism in adipose tissue → ↓ TG synthesis in adipose tissue

403
Q

State of CHO in Brain in Fasting state

A

The 1st few days of fasting: brain use glucose exclusively as a source of energy as it is produced via liver gluconeogenesis

404
Q

State of Lipid in Liver in Fasting state

A
  1. ↑ Fatty acids oxidation
    - by activation of CAT 1
  2. ↑ Ketone bodies (KB) synthesis
    - to supply KB for use as fuel by the peripheral tissues including the brain.
405
Q

State of Lipid in muscles in Fasting state

A

1st week of fasting: muscle uses FA and KB (Ketolysis) as sources of energy

406
Q

State of Lipid in adipose tissue in Fasting state

A
  1. ↓ Uptake of FAs
    - because the activity of Lipoprotein lipase of adipose tissue is low
  2. ↑ TAG degradation (lipolysis):
    - By activation of hormone sensitive TG lipase ,to form:

^FA that will be transported to tissues for use as a fuel.
^odd number FA and Glycerol that will be used as a gluconeogenic substrate by the liver.

407
Q

State of Protein in Liver in Fasting state

A

↑ protein catabolism to supply glucogenic amino acids for gluconeogenes

408
Q

State of Protein in muscles in Fasting state

A

1st few days of fasting: Increased protein catabolism of muscle protein to supply AA for gluconeogenesis.

409
Q

State of CHO in liver in fed state

A
  1. ++glucose phosphorylation By activation of glucokinase.
  2. ++glycolysis
  3. ++glycogenesis by activation of glycogen synthase .
  4. ++pentose shunt to supply NADPH+H for hepatic lipogenesis

—————–
5. – gluconeogenesis

410
Q

State of CHO in muscles in fed state

A
  1. insulin increase glucose uptake by muscles through GLUT 4
  2. ++glycogenenesis by activation of glycogen synthase
411
Q

State of CHO in Adipose tissue in fed state

A
  1. insulin increase glucose uptake through GLUT 4.
  2. ++glycolysis to increase supply glycerol 3P & acetyl CoA for lipogenesis.
  3. ++ pentose shunt to supply NADPH + H for lipogenesis
412
Q

State of CHO in Brain in fed state

A

Glucose is the only source of energy for brain in fed state

413
Q

State of lipid in liver in fed state

A
  1. ↑ fatty acid synthesis by activation of acetyle COA carboxylase
  2. ↑ triglycerides synthesis
414
Q

State of lipid in muscle in fed state

A
  • ↑ Fatty acid supply to muscles by insulin which ++ lipoprotein lipase which break TGs which are presented in chylomicrons
415
Q

State of lipid in adipose tissue in fed state

A
  1. TAG synthesis (lipogenesis).
  2. ↓TAG degradation (lipolysis) by inhibition of Hormone sensitive lipase enzyme
416
Q

State of lipid in brain in fed state

A
  • The brain has no stores of TAG.
  • Fatty acids can’t cross BBB.
417
Q

State of Protein in liver in fed state

A

↑protein synthesis in liver : to replace of any protein that may have been degraded , the liver can’t store protein like CHO and lipid.

418
Q

State of Protein in muscles in fed state

A

↑ protein synthesis: Amino acids are used for protein synthesis to replace the degraded protein.

419
Q

summary of states of nutrients in fed and fasting states

A
420
Q

what is the definition of starvation?

A

Complete deprivation of foods, salts and water.

421
Q

mechanism of starvation

OR

What is a starvation associated with?

A

Starvation is associated with decrease in insulin level and an increase in glucagon.

422
Q

what are the metabolic changes that occur during starvation?

A
  • At the starved state after the first week of fasting , changes occur in the utilization of fuel stores as the following :
  1. In prolonged fasting (2-3weeks): plasma KB become the primary source of energy for the brain

_________

  1. Muscle decreases its use of ketone bodies and increase fatty acid oxidation as its primary energy sources leading to increase ketone bodies conc. in blood ,so brain can take up ketone bodies as a source of energy.

____________

  1. Liver gluconeogenesis is decreased.

__________

  1. Several weeks of fasting: the rate of muscle catabolism ↓. Muscle protein is spared, so less muscle protein degraded to provide amino acids for gluconeogenesis.

______________

  1. Because of decrease conversion of amino acids to glucose , less urea is produced from amino acid nitrogen in starvation than overnight fasting.

____________

  1. The body uses its fat stores as its primary sources of energy during late starvation to conserve the functional proteins.

Y2B2 - Nutrition & Metabolism 📗 (5 decks)

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