N- Lipids, Carbos, Vitamins Flashcards
1
Q
Name 3 types of lipids
A
- Triacylglycerols- fuel
- Glycerophospholipids- membranes (glycerol based phospholipids)
- Cholesterol- membranes, steroids, bile salts
2
Q
Name some products of cholesterol
A
Bile salts- lipid digestion
Steroid hormones- communication
3
Q
Function of vitamins
A
vision, growth; Lipid soluble vitamins…
4
Q
What are triaglycerols?
A
Composed of= glycerol + three fatty acid chains
• Joined by ester bonds
- Fatty acids have variable length
- Can be saturated or unsaturated- creates kinks/bends, affects function/properties
- major dietary lipid
5
Q
Why are triaglycerides an efficient form of energy store
A
- Contain a lot of carbons
* Unlimited reserves of storage capacity for lipids? Excess fuel/ don’t burn enough? Can store in this form…
6
Q
2 sources of lipids
A
1- Dietary lipids; e.g. Lard
2- Endogenous lipids… synthesised in liver from glucose source
7
Q
What do lipases do?
A
Break down Triglycerides-> into fatty acids + monoacylglycerols
8
Q
What are Micelles?
A
Broken down triacylglycerol droplets surrounded by bile acids
(bile salts have charge so can break the fat up)
- Micelles are absorbed by gut lining cells (enterocytes) (small intestine)
9
Q
What happens to the Micelles once they have entered the SI lining
A
The triacylglyceride droplets are put back together again…
- Other components such as proteins are also embedded into the ball of fat
e. g. apoproteins and apolipoproteins (packaged as chylomicrons
10
Q
What are chylomicrons?
A
> Largest lipoprotein
90% lipid
Low protein-to-lipid ratio
Synthesised by absorptive cells of the intestinal lining and secreted into the lymphatic system.
Matures (from immature nascent form) in lymph system, as things are added.
(which joins the blood circulation at the subclavian vein)
11
Q
What makes up a chylomicron?
A
Ball of lipids + Encased membrane of phospholipids
(hydrophobic core- fats don’t like water)
+ cholesterol
+ Apoproteins
+ Apolipoproteins
+ Peripheral apoproteins
12
Q
Function of the proteins added to chylomicrons
A
The proteins help the chylomicron go to the right place- where the fat is needed
13
Q
What tissues need fat?
A
Fat tissue- adipose cells
Muscle- energy source
Storage…
14
Q
What enzyme digests triacylglycerides?
A
LPLs- lipoprotein lipase
15
Q
What cells make LPLs?
A
- Adipose
- Muscle
- Lactating mammary gland cells
(Where fat is needed/where it goes)
16
Q
What hormone regulates LPLs?
A
Insulin
17
Q
What happens to the products once the chylomicrons are broken down?
A
- Fatty acids are absorbed (diffusion) by the local cells
- The other remnants are absorbed by the liver to be recycled…
- the glycerol is recycled to liver.
- Lipid (cholesterol?) and protein remnants are used to form VLDLs and LDLs
18
Q
What are LPL enzymes? LPL- lipoprotein lipase
A
- Found on the surface of cells that want fat
- LPLs can recognise some of the apoproteins.
- Activated/ regulated by insulin
- Grab and chew up the
19
Q
What are endogenous lipids?
A
fats that we generate ourselves…
- Fatty acids synthesised in the liver
- Glucose is the source of carbons
- Reactions occur in the cytosol (cytoplasm)
20
Q
3 functions for fatty acids?
A
- stored as triacylglycerols
- oxidised as fuel
- used to make components of membranes
• Packaged with proteins to form VLDL (transported to other tissues in this form)
21
Q
How is it synthesised from glucose… and where?
A
In the liver: Glucose -> Glycolysis… Bit of the glycolysis pathway gives off Glycerol.
Glycerol is a key component of Triacylglycerol.
TG used to make VLDLs-> secreted into the blood stream.
22
Q
What is fatty acid oxidation?
A
During fasting, fatty acids become main energy source…
Long chain fatty acids released from adipose tissue and taken up by other tissues e.g. muscles for ATP.
Energy release pathways- main one is β-oxidation
23
Q
What stimulates the long-chain fatty acid release?
A
- reduced insulin levels… and
- increased glucagon
24
Q
How long does it take (roughly) for the body to replenish all its glycogen supplies
A
3 hours
- Until fat is used
25
How does Beta-oxidation occur?
- Fatty acids enter tissues (muscle) by diffusion
- These fatty acids are activated to fatty acyl-CoA using ATP
* Fatty acyl-CoA transported into mitochondria (matrix)
* Converted into acetyl CoA, producing NADH and FAD2H (donate electrons to electron transport chain)
* This is repeated until all carbons have been converted to acetyl CoA (2C)
* Acetyl CoA can enter TCA cycle (produces electron carriers and therefore more ATP)
26
Why do Fatty acids produce a lot of energy?
Fatty acids can be very long, containing many carbons. This produces a lot of energy!
- Only chews off 2 carbons at a time so produces lots of energy again and again…
27
Uses of fatty acyl CoA (3)
- Energy: beta-oxidation, ketogenesis
- Storage: triacylglycerols
- Membrane lipids: phospholipids, sphingolipids
28
What is Ketogenesis?
Metabolic process that occurs when body is low on glucose- burns stored fat instead (results in build up of acids called ketones within the body)
29
Where do we get cholesterol from?
- Synthesised
| - Obtained from diet
30
Uses of cholesterol?
- Cell membrane component
- Precursor of bile salts
- Precursor of steroid hormones
- Precursor of vit.D
- Major component of blood lipoproteins
31
How is cholesterol absorbed?
• Enters gut enterocytes predominantly by diffusion
• entry is regulated
• Enterocytes transport excess back into gut lumen
- cholesterol and bile salts excreted in faeces
32
Defects in proteins which transport cholesterol out can lead to...
cholesterol accumulation and cardiovascular disease
33
4 steps of cholesterol synthesis
- Occurs in liver cytosol
1. Acetyl-CoA -> Mevalonate
2. Mevalonate -> Isoprenes
3. Isoprenes (5C) -> Squalene (30C)
4. Squalene -> Cholesterol (final ring structure)
34
What is the rate limiting step of Cholesterol synthesis?
1. Acetyl-CoA -> Mevalonate
35
What is the enzyme involved in this first step?
HMG-CoA reductase
- Drug target for cholesterol synthesis (trying to prevent CVD)
- E.g. Statins
36
Statin function?
* Used to combat high cholesterol lveles in blood
* Competitively inhibit HMG Co-reductase for cholesterol synthesis
* Structural analogues of the natural substrate, compete for binding (have higher affinity)
37
Fate of Cholesterol... secreted from liver as= (3)
- Bile salts
- Biliary cholesterol
- Cholesterol esters
38
Where are bile salts stored/used? and function?
Stored in gallbladder
Secreted into gut
Aid digestion by emulsifying/breaking up fat
39
Where is biliary cholesterol used? function?
Secreted into gut
Can be reabsorbed
Important in digestion- can be converted into cholesterol esters
40
What are cholesterol esters?
Can be packaged in VLDL and transported around to tissues
41
When VLDLs are broken down, the remnant is converted to IDL and then LDL (high in cholesterol)... LDL fate...? =
(2)
1- Returned to liver to make more VLDLs
| 2- Taken up by other cells needing cholesterol: membrane synthesis, steroid hormone synthesis
42
Consequence to TOO much cholesterol in cells
* Excess LDL can be endocytosed by macrophages
* Macrophages have scavenger receptors: looking for things that shouldn’t be there
* Macrophages take up cholesterol-> form foamy cells -> form bumps in BVs
* Blood rushing by- can form a blood clot/thrombus
* This can cause inflammation and contribute to atherosclerosis (plaques forms)
* Blocked blood vessel?
43
What is glycolysis?
Glycolysis is the first step in the breakdown of glucose to extract energy for cellular metabolism.
-> ATP release!
44
Problem with TOO high blood glucose levels
Release of water from tissues due to osmotic pressure: dehydration, death
45
Problem with TOO low blood glucose levels
lack of fuel to produce ATP
- brain depends on glucose as fuel… coma
- red blood cells low on ATP; can’t provide oxygen to tissues… death
46
Hormones involved in blood glucose regulation
- Insulin
- Glucagon
- Adrenaline?
47
How do hormone levels change at meal times?
- Increase in insulin (insulin aim is to get glucose out of the blood…)
- Decrease in glucagon (although also peaks very slightly just after meal
48
What will a high ratio of Glucagon: Insulin cause?
Glucose to be release into blood stream
49
What will a low ratio of Glucagon: Insulin cause?
Low ratio= less glucagon and more insulin… will cause an uptake/storage of glucose (in glycogen form)
50
3 main sources of glucose: (2 and 3 are critical during fasting)
1. Diet
2. Glycogen degradation
3. Gluconeogenesis
Fatty acid oxidation provides energy but not glucose.
51
What is glycogen?
Branched chains of glucose.
• Joined by α1-4 linkages with branching created by α1-6 linkages
• One carbon is joined to protein – glycogenin
• Forms huge polymers
52
How is glycogen synthesised?
Requires UTP energy form
What is the enzyme involved called?
1. Glucose is transferred from UDP glucose to glycogenin
2. Glycogen synthase transfers glucose from UDP glucose to growing chain
3. This forms α1-4 linkages
4. When 11 residues is reached, 6-8 are cleaved off and rejoined by α1-6 linkages by branching enzyme
53
Glycogen Degradation- carried out by 2 enzymes: what are they called? + function?
1. Glycogen phosphorylase
- removes glucose molecules at end of chains
2. Debranching enzyme
- acts as transferase, removing glucose molecules near branch point
- also cleaves branch point
54
Glycogen function?
* Major storage form of carbohydrate
* Acts as source of glucose for ATP generation
* Serves different function in muscle and liver
55
Different in liver and muscle due to different requirements
- What happens in each?
* In liver glycogen metabolism regulates blood glucose levels
* In muscle it responds to changes in energy (ATP) needs
56
What hormones regulate glycogen metabolism in the liver?
- Insulin (causes release of glucose by glucagon degradation)
- Glucagon
- Adrenaline
57
What might stimulate glycogen degradation in the muscle (for energy release)
- Low ATP levels (high AMP levels)
- High Calcium
- High Adrenaline
58
Disorders of glycogen metabolism- causes?
• Can be caused by mutations in a number of enzymes
* May only affect liver enzymes or muscle enzymes
* Differing severity
59
What process happens if glycogen stores are exhausted? How else to make glucose?
Gluconeogenesis-> makes glucose!...
uses protein as an energy source! Skeletal muscle! Last resort (non-carbohydrate sources)
- Occurs only in liver
60
Gluconeogenesis precursors: (non-carbohydrate sources of glucose)...
- Amino acids – mainly alanine but others
- Lactate – produced during intense exercise
- Glycerol – derived from triacylglycerols
- Propionate – derived from fermentation of fibre
61
Two main regulatory factors of Gluconeogenesis?
1- substrate availability
| 2- activity of key enzymes
62
What substrate levels promote gluconeogensis?
(Low insulin/glucose levels stimulates release of...)
- Glycerol from adipose tissue
- AAs from muscle
- Intense exercise releases lactate from muscle
63
Three key regulatory steps of gluconeogenesis?
• Can be allosteric or at level of gene expression
i) Pyruvate -> phosphoenolpyruvate
ii) Fructose 1,6-bisphosphate -> Fructose 6-phosphate
iii) Glucose 6-phosphate -> Glucose
64
How does body get energy it needs for functioning...
- Glucose from diet -> Broken down via glycolysis
- Gluconeogenesis can make glucose... (AAs, lactate, glycerol, propionate)
- Fatty oxidation (break down of fat to release energy)
65
What are vitamins?
* Chemically disparate (dissimilar/different/unalike)
* Organic compounds (trace elements & minerals: inorganic)
• Diverse functions
- Essential for normal body function
• Deficiency may cause disease
* Needed in small amounts (μg or mg/day)
* Do not provide energy
* Most supplied in diet
* Some can be synthesised (D- sun; B and K- gut bacteria)
66
List a bunch of functions of vitamins
- Coenzymes
- Hormones
- cell signalling
- Antioxidants
- Regulators of growth and differentiation
67
What can affect low levels of vitamins?
- Biological availability & Absorption of vitamins
* Reduced absorption can lead to deficiency
* Properties of the food eg low in fat
* Pre-existing disease
* Drugs may compete for absorption, kill bacteria ( gut bacteria that produce the vitamins)
68
What diseases affect Vitamin levels
celiac (impaired fat absorption- needed for vit store?)
gastritis (low acid environment affects B12)
69
What is RDA?
Recommended daily allowance
| • RDA- ‘an intake that is adequate to ensure the requirements of all healthy people are met’
70
Who might vary from RDA?
- Children
| - Pregnant women e.g. Folate!
71
What is NRV?
nutrient reference value
72
What are the 2 groups of vitamins?
Fat-soluble and Water-soluble
In general fat soluble can be stored, water soluble not.
73
Name 4 fat soluble vitamins
* Vitamin A
* Vitamin D
* Vitamin E
* Vitamin K
ADEK
74
Name 2 water soluble vitamins
B and C
75
Functions of Vitamin A
"Retinoids" = active form
Sight... binds proteins to retina to form visual pigments.
- Nuclear modulator of gene expression
- Cell proliferation
- Differentiation (esp epithelia)
- Development
76
Symptoms of vit.A deficiency?
- Blindness
- Impaired resistance to infection
- Night blindness
- Xerophthalmia
- Keratinisation of conjunctiva epithelial cells
77
Functions of Vit. D
Must be metabolised within body to active form.
- Maintenance of plasma calcium conc
- Steroid hormone activating nuclear receptors
78
What is D3?
Calciol/ Cholecalciferol
79
What is D2?
Ercalciol/ Ergocalciferol
80
What is Calcitriol?
Calcitriol is a synthetic physiologically-active analog of vitamin D, specifically the vitamin D3 form. Calcitriol regulates calcium in vivo by promoting absorption in the intestine, reabsorption in the kidneys, and, along with parathyroid hormone, regulation of bone growth.
"active vit. D3"
81
How does vit. D regulate Ca levels?
Overall: increase in blood Ca!
vit.D NEEDED for Ca absorption...
- Stimulates Ca and PO absorption in the small intestine
- Renal Ca reabsorption
82
How does vit. D regulate bone mineralisation?
- Controlled by Ca and Po availability
- • Osteoblasts have receptors for Calcitriol (active metabolite of vitamin D)
• Promotes formation & mineralisation of bone
83
Vitamin D deficiency, symptoms:
Painful weak bone disorders:
- Rickets
- Osteomalacia
- Failure of bone mineralisation
84
Rickets stats?
* Eradication by supplementation in 1950s
| * 1 in 5 people in the UK deficient (2016)
85
How might racial genetic predisposition cause vitD deficiency?
defect in calcitriol hydrolase: no calcitriol
86
What is vit. E used for?
Antioxidant
(traps free radicals)
Affects cell signalling (inactivates protein kinase C which controls protein phosphorlyation)
87
What is vit. K used for?
- Coenzyme
- Binding of proteins to membrane phospholipids
- Klotting! Coagulation... "vit. K dependent proteins"
88
What are the vitamin K dependent proteins involved in blood coagulation ?
thrombin,
factors VII, IX & X,
protein C, S & Z
89
Where does clotting occur?
• Clotting occurs on phospholipid surfaces...
And vit. K needed for Binding of proteins to membrane phospholipids...
90
VitK deficiency (esp in new borns) can lead to?
haemorrhagic disease
91
Name an anticoagulant
Vit.K antagonists... Warfarin
92
What are the B vitamins (1 to 12)
```
Thiamin (B1),
ribofavin (B2),
Niacin (B3),
B6,
Folic acid (B9),
B12,
pantothenic acid (B5)
```
93
What is B1 called?
Thiamin
94
What is B2?
Ribofavin
95
What is B3?
Niacin
96
What is B9?
Folic acid
97
Functions of B vitamins?
* All co-enzymes (co-factors):
* ‘Helper molecules’
* Non-proteins but bind to protein (enzymes)
* Required for protein’s biological activity
98
Thiamin (vitamin B1) function?
• Co-enzyme in central energy yielding pathways
Helps produce ATP
- Neutransmitters, myelin
Deficiency: lack of ATP, weakness, stiff
99
Riboflavin (vitamin B2) function?
• Electron carriers, metabolism, redox reactions
- Remains bound to enzyme
- Deficiency is common but not usually a problem
100
Niacin (B3) function?
• Precursor of co-enzymes NAD and NADP
Electron carriers in metabolic redox reactions
* Synthesised from dietary tryptophan
* Deficiency rare, Pellegra
101
Vitamin B6 function?
• Amino acid metabolism (transamination)
102
Vitamin B12 & Folate (B9)
* Coenzymes
* DNA & myelin synthesis
* Deficiency- anaemia & neurological damage
* Folate supplementation in pregnancy
103
Vitamin C function?
Anti-oxidant
Role in 2 enzyme classes...
- Nor/Adrenaline synthesis
- Maturation of CT
104
Where is vitC found?
"Ascorbic acid "
Oranges?
Citrus fruits
105
Vit Deficiencies and the oral epithelium
* Rapid turnover of epithelium ( in oral cavity) makes it sensitive to nutritional deficiencies
* Vitamins involved with: wound healing, bleeding, resistance to infection, bone/tooth Ca2+
106
Vitamin deficiency symptoms of the face
- Malar pigmentation
- Nasolabial seborrhae (red itchy rash)
- Lack of colour
107
Vitamin deficiency symptoms of the lips
- Cheilosis
| - Angular fissures
108
Vitamin deficiency symptoms of the gingiva
and which vit?
Spongy, bleeding, abnormal redness
caused by vit C!!
109
Vitamin deficiency symptoms of the tongue
```
Glossitis- red fissured tongue (lots of Bs)
Pale
Atrophic
Smooth/slick
"Filiform papillary atrophy"
Magenta colour (B2)
```
110
What causes filiform papillary atrophy?
Folate B9
111
Most oral manifestations cause by which B vitamin deficiency?
Niacin B3 (mostly this)
Ribofavin B2
B6
