Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Metabolism > Haem metabolism > Flashcards

Haem metabolism Flashcards

(48 cards)

Start Studying
1
Q

importance of haem

A
  • oxygen transport and storage (haemoglobin, myoglobin)
  • oxygen metabolism (oxidases, peroxidases, catalases, hydroxylases)
  • electrons transfer and drug metabolism (cytochromes)
  • signal transduction (nitric oxide synthase)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

why must iron bind to haem

A

free iron is toxic

iron binds to haem and haem is always bound to protein in circulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

where is haem synthesised

A

most cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what metabolise the largest quantities of haem

A

liver and erythron

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

how is haem transported

A

in plasma, bound to haemopexin or as haemoglobin bound to haptoglobin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

where is the main site of haem breakdown

A

macrophages, liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what is haem broken down to, and what happens next

A

bilirubin which is transported to the liver for conjugation and excretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

principle site of haem synthesis in all tissues

A

erythroid cells ~85%

hepatocytes ~15%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what is haem required for in hepatocytes

A

incorporation into cytocrhome p450

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

where is majoriy of body’s iron content

A

80% of body’s iron is incorporated into haemoglobin in developing RBC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

overview of haem biosnythesis

A
  • highly conserved process
  • 8 enzymes
    • 4 in the mitochondira
    • 4 in the cytoplasm
  • synthesis starts in the mitochondria
  • metabolite moves out into the cytoplasm
  • finishes in the mitochondria
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Rate limiting step of haem biosynthesis

A

Conversion of
succinyl CoA + Glycine –> aminolevulinic acid
- by action of ALAS enzyme (hence rate limiting)

succinyl CoA and glycine are in the mitochondria
aminolevulinic acid moves out to cytoplasm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

ALAS

A

aminolevuninc acid synthase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what is the rate limiting enzyme of haem biosynthesis

A

ALAS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Where does haem biosynthesis begin and with what

A

in the mitochondria with glycine and succinyl CoA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

basis of haem biosythesis

A
  • glycine + succinyl CoA -> ALA
    enzyme: ALAS
    location mitochondria
  • ALA -> Porphobilinogen
    enzyme: ALAD
    location: cytoplasm
  • Porphobilinogen -> hydroxymethylbilane
    enzyme: PBDG
  • hydroxymethylbilane -> Uroporphyrinoegn III
    enzyme: URO3S
  • Uroporphyrinoegn III -> coproporphyrinoegn III
    enzyme: UROD
    -coproporphyrinoegn III -> protoporphyrinogen IX
    enzyme: CPO
    location: mitochondria
  • protoporphyrinogen IX -> protoporhyrin IX
    enzyme: PPO
    -protoporhyrin IX -> HAEM
    enyzyme: FECH
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

ALA

A

Aminolevulinic acid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

ALAS

A

Aminolevulinic acid synthetase = rate limit step

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

ALAD

A

Aminolevulinic acid dehydrate (2x)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

PBDG

Study These Flashcards
A

porphobilinogen deaminase
(4x)
deamination

21
Q

URO32

Study These Flashcards
A

uropophyrinogen III sythetase

-cyclisation of HMB

22
Q

UROD

Study These Flashcards
A

uropophyrinogen III decarboxylase

  • change in side chains
  • removal of 4 carboxylic groups of the acetic side chains AKA decarboxylation of methyl groups
23
Q

CPO

Study These Flashcards
A

copropophyrinogen oxidase
- oxidative carboxylation of propionate groups of pyrrole rings A and B
AKA 2 propionate groups -> 2 vinyl groups

24
Q

PPO

Study These Flashcards
A
  • protoporphyrinogen oxidase
  • in mitochondria
  • oxidisation
25
FECH
- Ferrocheletase - insertion of iron in protoporphyrin ring - in mitochondrion = haem
26
types of ALA synthase in mammals
regulation of haem biosynthesis in mammals occurs via 2 distinct pathways - nonerythroid cells - erythroid precursor cells
27
regulation of haem biosynthesis in non-erythroid cells
housekeeping = ALAS-1 - transcriptional regulation via haem - also reguation of mitochondiral import of ALAS by haem - direct inhibition of the enzyme by haem
28
regulation of haem biosynthesis in erythroid cells
eALAS = ALAS-2 - translational regulation - iron responsive element (IRE) located in the 5' end of mRNA - iron regulatory protein (IRP) interact with IRE and inhibit translation
29
regulation of haem synthesis
- feedback mechanism is important - Inhibition of ALAS is well established - transcriptional control by heam indicated, as well as control of mitochondrial import - need to coordinate iron supply in erythroid cells - 5' IRE on eALAS mRNA - other mechanisms are important but not well understood
30
why is regulation of haem synthesis important
if excess haem produced, degradation occurs which willl release free iron causing iron toxicity
31
how is haem degraded
- haem is oxidised which opens the ring by, by action of ER enzyme HO-1 - oxidation occurs on specific carbon producing the liner tetrepyrole biliverdin, ferric iron (Fe3+) and CO - tetrepyrole biliverdin reduced to bilirubin
32
what is HO-1
Heam-oxygenase-1 | enyme from the endoplasmic reticulum which oxidises haem ring to open it, as part of degradation
33
ferric iron
Fe 3+
34
what happens to bilirubin produced by haem degradation
- bilirubin conjugated with gucuronic acid = bilirubin diglucuronide and excreted in the bile - some is reabsorbed and excreted in urine = yellow - rest is metabolised in colon by bacteria; intestinal bacteria metabolise bilirubin to urobilirubin
35
biological activity of reaction products from haem degradation
- CO has anti-inflamatory, anti-thrombotic and anti-apoptopic effects - biliverdin and bilirubin have anti-oxidant properties
36
what are porphyrias
group of disorder caused by deficiencies in the activity of enzymes within haem biosynthesis pathway - porphorias and/or their precursos (ALA, PBG) are abnormall produced in excess and accumulate in tissues and are excreted in urin and stool - purple, red pigment
37
classification of porphyrias
- hepatic - erythropoetic - acute hepatic - cutaneous porphyrias
38
acute hepatic porphyrias
clinical characteristics: neurological disturbances biochemical characteristics: an overproduction of porhyprin precursos ALA and PBG
39
porphoryn precursos
ALA and PBG
40
cutaneous porphyrias
clinical characteristics: cutaneous photosensitivty biochemically characteristics: excessive production of porphorias
41
Acute Intermittent Porphyria (AIP)
- partial porphbilinogen deaminase (PBDG) deficiency - Triggered by drugs that induce agents hepatic cyctochrome p450 - Causes a reduced haem level which disrupts regulation of ALAS by haem - leads to accumulation of ALA and PBG - neurological and psychiatric symptoms and severe abdominal pain - reducing ALA and PBG, and excretion by intravenous heamatin injection is effective
42
Porphyria Cutanea Tarda (PCT)
- most common of all forms of the porphyrias - heterogenous group of cutaneous porphyric diseases due to UROD deficience - inherited or more commonly acquired
43
most common form of porphyrias
porphyria cutanea tarda
44
what can lead to acquiring PCT
- increased amunt of hepatic iron (HFe) - alcohol, chlorinated cyclic hydrocarbons - hepatitis C and/or HIV virus infections - oestrogens - smoking - low vit C and carotenoid status
45
Variegate porphyria (VP)
- south african genetic porphyria - heterozygouse deficiency in PPD activity - inherited in autosomal manner - biochemical marker is elevated concentration of fecal protoporphyrin IX - plasma shows a fluorescnce emission when excited by long UV light
46
what is elevated concentration of fecal protoporphyrin IX a biomarker for
Variegate porphyria (VP)
47
photodynamic theory
- well established for certain skin cancers - cells mae sensitive to light by treatment with ALA, either topically or by injection - after time, protoporphyrin IX forms and light shone on cancer to kill cells - can also be used for skin disorders - being researched for treatment of other cancers
48
Cellular iron metabolism is regulated through the IRE/IRP system, which acts at the level of
translation

Metabolism (11 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions