pathophysiology

Pathophysiology

WAZZZZZZUP Broritos,

TODAY we are going to talk about pathophysiology

The homogentisate 1,2-dioxygenase(HGD) requires 6 subunits to form 2 HGD trimer which in turn forms a bioactive HGD hexamer. The HGD uses Fe2+ and O2 to cleave the aromatic ring of the homogentisic acid(HGA)to form maleylacetoacetic acid.However, a mutation in one or more of the 6 subunits will interfere with the formation of the HGD trimer.Thus, there will not be any bioactive homogentisate 1,2-dioxygenase.

That is all for today !!! Hope abit of pathophysiology was interesting

Peace out

A&K connections

Genetics

Genetics

Hey broritos, Hope u guys had a great Christmas

Today, we are going to talk about genetics. Fret not cuz today’s genetics part will be very straight forward and interesting at the same time.

Now I am going to talk about the location of a gene or in other words locus

Firstly we must learn how to read cytogenetic location of a gene!! So here is a diagram to help u guys with it :)

Cytogenetic location:7q31.2.

We are using CFTR(Cystic fibrosis transmembrane conductance regulator) as an example.The first number 7 indicates the chromosome number. In humans we have 23 pairs of chromosome. So, in this case the CFTR gene is located on the 7th chromosome.

The q represents the arm of the chromosome. Every chromosome has two arms which are p and q. The p represents the short arm and q represents the long arm. Both arms are “divided” by a centromere.Hopefully, the diagram below shows a better illustration.

Next, the number 3 represents the region and 1 represents the band. These region and bands are obtained when the chromosome is stained in a certain way.Then, the bands are visualized under microscope.(region and band number count starts from centromere and ends at the telomere)  After the region and band number, there will be a number after a decimal point, this number indicates the subband which can be visualized under microscope with higher resolution within the normal bands.

Hopefully the above explanation gives a clearer idea on gene location

SO Where is HGD gene found??

Cytogenetic location : 3q13.33

Other than the cytogenetic location, there is also the molecular location which use base pairs to locate the gene.  For the HGD gene, the gene is located base pairs 120,628,167 to 120,682,570 on chromosome 3

Hope the gene location was educational. Now, we are going to talk about autosomal recessive

Remember us saying that the gene is transferred to the affected individual in an autosomal recessive manner!!

Autosomal refers to a mutation in one of the first 22 non-sex chromosome.

So what is recessive?

Genes come in pairs. Therefore, Recessive means that both genes must be defective for the disease to occur.

Lets use this diagram to help us understand recessive

X-dominant gene

x- recessive gene.

XX- unaffected by disease and not a carrier

Xx-unaffected by disease and is a carrier

xx- affected by disease

Only a child with xx be affected with disease.Thus, if both parents are carriers to a defective gene, the child will be 25% likely to inherit the disease, 50% likely to be carriers and 25% likely not to carry the mutant gene.

SOOO , A person must be very unfortunate to inherit an autosomal recessive disease. More so , if it is a rare disease like Alkaptonuria.

WHY ALWAYS ME ??

Currently over 100 mutation of HGD gene has been identified

That's all from us today

Next blog: Pathophysiology

PEACE-OUT

A&K connections

History of alkaptonuria

Welcome back Broritos to a very special blog from your own A&K connection!

Oh but before I forget…

Merry Christmas Eve! XD Yayyyy!!!

Today’s blog is a little less on the hard science and more the fun part of it! In fact, we are going to take u guys through a very short history “lesson” on Alkaptonuria. Don’t worry guys, this’ll be a lot more fun than history lessons in secondary school!

 

Why you ask? Well that’s because we made you Broritos a special video on the history of Alkaptonuria as your Christmas present! Enjoy and don’t forget your delicious snacks! :D

Of course for those of you who are interested to know more in detail, I’ve written it down below for you guys:

Alkaptonuria was first discovered by a british physician named Sir Archibald Garrod (1857-1936) in 1901. He showed great interest in his patient’s urine and one day, examined a three-month-old patient called Thomas P. He saw an unusual bluish black stain on the diaper (remember that during those times Alkaptonuria was an unknown disease). Later, Thomas’ two other siblings were born and also had the same black diaper stains. Thomas’s parents were actually cousins (unaffected from disease) and their mothers were siblings. One day, Sir Garrod read bateson’s description on Mendel’s work and soon everything becomes much clearer. He discovered that Thomas’s parents each contributed a mutated allele causing thomas and his siblings to inherit the disease.He credits Mendel’s law for his sudden realization. SIr Garrod was the first pioneer to link hereditary to metabolic linked diseases. He called such diseases “inborn errors of metabolism”. Just like many other great scientists,Sir Garrod’s work was not recognised and appreciated during  his lifetime. SOOOO SAD:(

(Fun fact: Sir Garrod’s father was the first person to discover abnormal uric acid metabolism and his daughter was the first women to hold an oxbridge chair

(Another fun fact: An egyptian mummy named Harwa suffered from Alkaptonuria during 1500 BC)

ALRIGHT BRORITOS!! Hope u had a fun history lesson

PEACE OUT

complications from Alkaptonuria

Hola broritos,

Hope you guys enjoyed our last blog :) Today we are going to learn something new and more interesting

In my previous post I mentioned that Homogentisic acid(HGA) is toxic to the body and causes three major complications.

So now, lets talk about how HGA causes the three major complications

Lets go bros!!!

The first complication is black urine, and if you’ve been reading our blog, you’ll know it’s because of HGA in the urine. HGA gets readily oxidised when exposed to oxygen from air causing it form a new compound called Benzoquinone acetic acid (BQA). The substance BQA causes the urine to appear black. However, the actual darkening of urine will only occur after several hours and many individuals never observe any change in colour of urine! They are  unaware of their genetic disease until other complications start to appear. How scary is that?!           ````````````````````````````````````````````````````````````````````````````````````````````````````````````````````

Ew! Imagine how terrifying that would be if you saw that in your toilet!

But enough scary thoughts of black urine, look at how cute this little fella is! Awwww :3 Shout out to the awesome Adventure Time!

The second complication is Ochronosis (Bluish black pigmentation of connective tissue). Ochronosis occurs after the age of 30.This is when most individuals will start to recognize that they inherit Alkaptonuria. Brown pigment is observed at the sclera of the eyes. Brown pigment deposition can also happen in the conjunctiva and cornea. Fortunately, the brown pigments will not have any negative impact on the vision. Another organ with pigmentation is the ear helix. A bluish gray pigment can be found at the ear helix.At the same time, the ears may start to calcify. Purple or dark discolouration forms on the hands of the affected patients and pigments can be released through sweat which can stain the clothes.

I’d hate to imagine what his sweaty clothes would be like if he had Alkaptonuria! Yuck! Dx

The third complication is Osteoarthritis. Arthritis is a form of joint disorder that involves inflammation of one or more joints. This complication rises when an affected individual reaches 30-40 years old. Osteoarthritis occur when BQA binds to the bond causing them to be black and brittle. Osteoarthritis begins in the spine, causing the spine to narrow and forcing the it to go through ankylosis spondylitis ( vertebrate of spine fusing together). This limits the spine’s flexion. Afterwards, the osteoarthritis spreads to other part of the body such as knees, shoulders and hips. The bones start to degrade and break into tiny fragments. This is a very painful process and patients usually complain of their bones grinding against one another.
 

“Granny, no! Your arthritis!” *snap* D:

Here’s a fan service to all you Cat lovers ;3

But unfortunately, these are the ONLY the three common complications arising from Alkaptonuria. (So horrible to think there’s more! D:) Other possible complications include heart, kidney and prostate (OUCH!) problems. HGA gets deposited on the valves of the heart causing them to be brittle and black as well.Moreover, it can also weaken and stiffen the blood vessels which increases the risk of heart diseases. This usually affect patients of 60 years of age and above. It can also lead to renal and prostate stones.

For any of you Lord of the Rings fans. I know I am ;)

Thank you, Hope u broritos enjoyed our blog

Peaceout

A&K connection

The basics of Alkaptonuria

Welcome back Broritos to another exciting blog from your friends the A&K connection!

Today we’ll be talking all about the basics of Alkaptonuria, so don’t forget to grab your snacks!

Alkaptonuria or “Black urine disease” is a rare inherited disease that is passed on from parents in an autosomal recessive manner. In this disease. individuals lose their ability to metabolize tyrosine during a stepwise breakdown in the tyrosine degradation pathway.Thus, the body starts to accumulate an intermediate called homogentisic acid.(HGA). HGA is a toxic compound to the human body.The mutation of the HGD gene is the sole cause of this disease because it codes for an enzyme called homogentisate 1,2-dioxygenase. This enzyme is required in the tyrosine degradation pathway to breakdown HGA to maleylacetoacetic acid.Therefore, mutation in the HGD gene would produce a dysfunctional homogentisate 1,2-dioxygenase which loses its ability to convert HGA to maleylacetoacetic acid. Soon, the body starts to accumulate HGA toxic substances which causes three major and several other possible complications.

But argh, it all seems so complicated! D:

So i got a pathway diagram just for you guys! :D

~ Fun fact: there is 2000 times more HGA in affected individuals compared to unaffected individuals ~

See, it’s not so complicated when you’re with us!

So once again, thank you for reading my blog, and I’ll see you in the next post where we talk about the three major the complications (and genetics) of Alkaptonuria! 

Peace out Broritos! :D

Introduction

Why hello there everyone!! Welcome to our new blog which is about a metabolic disease called Alkaptonuria. This blog is created as part of our Medical biochemistry project and the motive of this blog is to educate everyone about Alkaptonuria. Before I start talking about this disease, let me just do a small intro. My name is Aravin and my project partner is Kyle (AKA Finnigan). We are year 2 biomedical students from Ngee Ann Polytechnic. In this blog, we are going to talk about Alkaptonuria, the history of Alkaptonuria, its symptoms, diagnosis, prognosis, etc… Hope you guys enjoy and learn at the same time.