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Prezi Biochemistry

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Jim Kingsley

on 26 April 2014

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Transcript of Prezi Biochemistry

Acetyl CoA
CoASH
Citrate
H2O
Citrate Synthase
Isocitrate
aconitase
CO2
NAD+
NADH + H
Isocitrate Dehydrogenase
CO2
CoASH
NADH
H+
Succinyl CoA
NAD+
alpha- Ketoglutarate
Dehydrogenase
CoASH
GDP + Pi
GTP
Succinate
Thiokinase
Succinate
FAD
FADH2
Fumarate
Succinate Dehydrogenase
Oxaloacetate
Malate
H2O
Fumarase
Malate
Dehydrogenase
Nad+
H + NADH
Pyruvate
CO2
NAD+
NADH + H
Pyruvate Dehydrogenase
ADP
ATP
Phosphoenolpyruvate
H2O
2-Phosphoglycerate
enolase
Pyruvate
Kinase
3 - Phosphoglycerate
Phosphoglycero-
mutase
1,3-Bisphosphoglycerate
ADP
ATP
Phosphoglycerate Kinase
Glyceraldehyde 3-Phosphate
Pi + NAD
NADH + H
G3P Dehydrogenase
Dihydroxyacetone
Phosphate

Triose Phosphate
Isomerase
Fructose 1,6 bisphosphate
Fructose 6 - phosphate
ATP
ADP
Phosphofructokinase - 1
Glucose 6 - Phosphate
Phosphoglucose Isomerase
Glucose
ATP
ADP
Hexokinase
Glucokinase
Aldolase A
Glucose 6 - Phosphate
Insulin
Fructose 1,6 -bisphosphate
Alanine
&
Phosphorylation by PKA
Alanine
Aminotransferase
Pyridoxal
Phosphate
NADH
NAD+
Lactate Dehydrogenase
Lactate
Acetyl CoA
CoASH
Citrate
H2O
Citrate Synthase
Isocitrate
aconitase
CO2
NAD+
NADH + H
Isocitrate Dehydrogenase
alpha - Ketoglutarateα
CO2
CoASH
NADH
H+
Succinyl CoA
NAD+
alpha- Ketoglutarate
Dehydorgenase
CoASH
GDP + Pi
GTP
Succinate
Thiokinase
Succinate
FAD
FADH2
Fumarate
Succinate Dehydrogenase
Oxaloacetate
Malate
H2O
Fumarase
Malate
Dehydrogenase
Nad+
H + NADH
Pyruvate
CO2
NAD+
NADH + H
Pyruvate Dehydrogenase
ADP
ATP
Phosphoenolpyruvate
H2O
2-Phosphoglycerate
enolase
Pyruvate
Kinase
3 - Phosphoglycerate
Phosphoglycero-
mutase
1,3-Bisphosphoglycerate
ADP
ATP
Phosphoglycerate Kinase
Gylceraldehyde 3-Phosphate
Pi + NAD
NADH + H
G3P Dehydrogenase
Dihydroxyacetone
Phosphate
Triose Phosphate
Isomerase
Aldolase
Fructose 1,6 bisphosphate
Fructose 6 - phosphate
ATP
ADP
Phosphofructokinase - 1
Glucose 6 - Phosphate
Phosphoglucose Isomerase
Glucose
ATP
ADP
Hexokinase
(Glucokinase in Liver)
Aldolase
Glucose 6 - Phosphate
Insulin
Must Remeber to
Include Regulation of
PFK1
Fructose 1,6 -bisphosphate
Alanine
&
If Phosphorylated in the Liver
Alanine
Aminotransferase
Alanine
Pyridoxal
Phosphate
NADH
NAD+
Lactate Dehydrogenase
Lactate
ATP
CO2
ADP + Pi
Biotin
Pyruvate
Carboxylase
Phosphoenolpyruvate
Carboxykinase
Fatty Acids
Remeber to Explain Why and How this stimulates Gluconeogenesis
Pi
Fructose 1,6
Bisphosphatase
Pi
Glucose 6-phosphatase
Acetyl CoA
Activated Transcriptionally
Ribulose 5- phosphate
2 NADP+
NADPH
CO2
Multi-Step Reaction:
Glucose 6- Phosphate dehydrogenase
6-phosphogluconolactone hydrolase
& 6-phosphogluconate dehydrogenase
Ribose 5- phosphate
Nucleotide Biosynthesis
Isomerase
Glyceraldehyde
Fructose 1-Phosphate
Aldolase B
Fructose
ADP
ATP
Fructokinase
ADP
ATP
Triose Kinase
Glucose 1 - Phosphate
Phosphoglucomutase
PPi
UTP
UDP - Glucose
UDP
Glycogen
UDP- Glucose
pyrophosphorylase
Glycogen Synthase
Glycogen Phosphorylase
2 Pi
Galactose 1 - Phosphate
UDP Galactose
UDP Glucose
epimerase
Galactose 1- P
Uridyl transferase
ADP
ATP
Galactose
Galactokinase
Glycogen
Synthesis

Glycogen
Degradation

PPP
Pathway

Fructose & Galactose Metabolism
Glycolysis
TCA Cycle
Argininosuccinate
Arginine
H2O
Urea
Citrulline
NH4 + CO2
Carbamoyl
phosphate

2 ATP
2 ADP
Carbamoyl phosphate
synthetase 1 (CPS1)
Ornithine
Transcarbamoylase
Argininosuccinate
synthetase
ATP
PPi
Ariginosuccinase
Arginase
Urea Cycle
CoQ
Cytochrome C
Complex 1
Complex 2
(Succinate Dehydrogenase)
Complex 3
Complex 4
Complex 5
ATP Synthase
NADH
NAD+
FADH2
FAD
1/2 O2
H2O
H+
H+
H+
ADP + Pi
ATP
Electron Transport Chain
Transamination
Asparagine
Aspartate
Glutamine
Proline
Ornithine
Serine
Serine dehydratase Pyridoxal Phsophate
NH4
H2SO4
Cysteine
Glycine
Alanine
TH4
Glycine
Cysteine
Methionine (S)
+ H2O
Glutamine
Glutamate
Glutamate
Dehydrogenase
Glutamate
semialdehyde
Threonine
FH4
alpha -
Ketoglutarate

Phenylalanine
Phenylalanine
hydroxylase
Tyrosine
Homogentistic Acid
acetoacetate
Glutaminase
NH4+
NADH, H+
Histidine
Methylmalonyl CoA
Propionyl CoA
NH4
Threonine
dehydratase
alpha
ketobutyrate
Cystathionine
Cysteine
Homocysteine
Serine
Methionine
SAM
S- Adenosyl homocysteine
CH3
B12- CH3
B12
5-CH3-FH4
FH4
isobutyryl CoA
CO2
alpha -
Ketoisovalerate
alpha keto acid
dehydrogenase
Valine
2-Methylbutyryl CoA
CO2
CO2
alpha Keto Beta
methylvalerate
Isoleucine
CO2
Acetyl CoA
Acetoacetate
HMG CoA
CO2
Isovaleryl CoA
CO2
alpha
Ketoisocaproate
Leucine
Ketogenesis
TH4
ATP
Oxaloacetate
Malate
Citrate Lyase
Acetyl CoA
Insulin
ATP
Cytosolic Malate Dehydrogenase
Malic Enzyme
Malonyl CoA
Fatty Acid
Synthase

Palmitate (saturated)
ATP
Biotin
Acetyl CoA
Carboxylase
Phosphorylation
dephosphorylation
&
citrate
Hexokinase is found in most tissues
Functions even when Blood Glucose Levels are low
Has LOW Km for Glucose, THUS it has a high Vmax
Glucose -6-P
Fructose -6-P
Fructose -1,6- BP
Fructose -2,6-BP
Pi
ADP
PFK2
PFK2 -P
ADP
ATP
Pi
Phosphatase
Protein
Kinase A
PFK-1
AMP
ATP
&
Citrate
AMP accumulates in muscle during exercise,
which will increase PFK-1 Activity which will
increase energy production in the muscle cell
through Glycolysis.
When ATP levels are high, the cell does not need more ATP
Accumulation of Citrate in the cell indicates that there are enough TCA cycle substrates and thus ATP is not in high demand.
An inactivated Pyruvate Kinase
drives gluconeogenesis.
Lactate Dehydrogenase consists of 4 subunits. Each of these subunits can be either of Muscle type (M) or Heart type (H)

The Five Isozymes that occur are:
1. MMMM
2. MMMH
3. MMHH
4. MHHH
5. HHHH

Depending on which tissue you are looking at in the body there will be a different isozyme
Lactate is the end product of energy production in hypoxic muscle cells & RBCs. Lactate is then mostly transported to Liver (majority) and Kidney for Gluconeogenesis. This cycle is the Cori Cycle
The purpose of Pyruvate Carboxylase
is to restock the intermediates of
the TCA Cycle.
Clinical Correlates
ATP Counting
ATP Production only through Glycolysis

1. Glucose molecule produces 2 Pyruvates. 4 ATPs are produced and 2 ATPs are used.

2. Additionally, 2 NADH's are produced which can be converted into 6 ATP (~4 ATP because of shuttle expense)

Net ATP for Glycolysis = 2 ATP
ATP Production from Glucose to Lactate

1. Glycolysis: Glucose to Pyruvate = 2 ATP

2. The 2 NADH produced by Glycolysis is consumed to convert Pyruvate to Lactate

Net ATP for Glucose to Lactate is 2 ATP
ATP Production from Glucose to CO2 and H2O

1. Glucose to 2 Pyruvate = 6 ATP (after ETC)
2. 2 Pyruvate to 2 Acetyl CoA = 6 ATP (after ETC)
3. TCA Cycle = 24 ATP (6 NADH, 2 FADH2, and 2 GTP)

Net ATP for Glucose to CO2 and H2O = 36-38 ATP




Although the precise numbers for ATP are important values to know for your exams, it is important to know that these numbers are not the same in everyone or in every tissue. There is variability due to genetic polymorphisms and different degrees of uncoupling. Always remember when you’re studying to know what values you will need for the exam, but also understand what is truly going on in biology, because that is what will benefit the patient the most.
Review Questions
DHAP
Glycerol -3- P
Glycerol -3- P
DHAP
FAD
FADH2
NADH
NAD+
NADH
NAD+
Oxaloacetate
Malate
Aspartate
Aspartate
Malate
Oxaloacetate
NAD+
NADH
The NADH used in these two transport shuttles
are derived from NADH produced in the cytosol,
usually from Glycolysis. Depending on which of
these pathways is chosen will determine how much
ATP can be produced from Glycolysis.

If the Glycerol Phosphate Shuttle is used, then 2 less
ATP are produced because of the energy requirements
of the transport. Therefore one glucose will produce 36 ATP.

If the Malate Aspartate Shuttle is used then no ATP is lost
during transport into the mitochondria and thus a
single glucose molecule can produced the full 38 molecules of ATP.
Gluconeogenesis
Clinical Correlates
Board Style Review Questions
Hypoglycemia
Lactic Acidosis
Intestinal Lactate Deficiency
Clinical Correlates
Clinical Correlates
1. Glycogen Storage Disease
Board Style Review Questions
Aspartate
Transaminase Reaction
Urocanate
NH4+
Alpha-Ketoglutarate
Oxaloacetate
Glutamate
Aspartate
Aminotransferase/
transaminase
pyridoxal phosphate (PLP)
Amino Acid 2
Alpha-Keto Acid 1
Alpha-Keto Acid 2
Amino Acid 1
aminotransferase/
transaminase
pyridoxal phosphate (PLP)
transaminase
Example:
Amino Acid manipulation: the
Transamination Rxn:
Histidase
The Alpha-Ketogluterate/Glutamate reaction provides a way to collect excess nitrogen. Nitrogen can also be released by this reaction.
Notice that Glutamate can be made from Alpha-Ketogluterate by either transamination or ammonia and glutamate dehydrogenase
. and are key amino acids that provide ammonia (NH3) for the urea cycle
Cholesterol and phospholipids
Following hi-carb meal
Released to blood and peripheral tissue
Lipoprotein Lipase
Taken up by liver via endocytosis
Bind receptors on cells of peripheral tissues to be taken up via endocytosis
Clinical Correlates
Synthesis of cell membranes and steroids
Activates acyl:cholesterol acyltransferase (ACAT)
Inhibits HMG CoA reductase and synthesis of LDL receptors
Ornithine
N-Acetylglutamate
1. A young child is found to have severe acidosis, vomiting, hypotonia, and neurologic deficits. Laboratory analysis reveals elevated levels of lactate and alanine. What enzyme is deficient in the young child?
(A) Pyruvate dehydrogenase
(B) Glutamate dehydrogenase
(C) Phenylethanolamine N-methyltransferase
(D) Lactate dehydrogenase
(E) Alanine aminotransferase
2. A five year old boy’s mother has recently found out she’s pregnant. The boy has glucose-6-phosphate dehydrogenase deficiency and is worried that his new sister might have the same disease. Both his mother and father have no clinical symptoms. Which of the following is true?

A. The new baby has a 25% chance of clinical disease
B. The new baby has a 50% chance of being a carrier
C. The new baby has a 50% chance of clinical disease
D. The new baby will be a carrier
E. The new baby will have clinical disease
3. In preparation for a trip to an area of West Africa, a student goes to his primary care doctor where she is given several vaccines and primaquine (malaria prophylaxis). When the student arrives in West Africa the people he is living with notices that his skin is yellow. What in his body is most likely to be decreased?

A. Oxidized form of Glutathione
B. NADH
C. Reduced Form of Glutathione
D. Ribose 5-Phosphate
E. Bilirubin
4. Which one of the following enzymes is only found in glycolysis?

A. Pyruvate kinase
B. Phosphoglycerate mutase
C. Enolase
D. Phosphoglycerate kinase
E. Glucose 6 phosphatase
5. A newborn vomits after each feeding of a milk-based formula and has failed to gain any weight. Your concern is that there might be a homozygous deficiency of galactose-1-phosphate uridyltransferase. If you as the provider decide to do nothing which of the following complications can occur

A. Baby will grow up in average percentile of weight and height
B. Vomiting will subside within a few months
C. Death in infancy
D. Death in adulthood
E. Increased risk for gastrointestinal neoplasia
6. Little Henry’s Mom buys Henry a popsicle when she is at the store. When Henry eats the popsicle, which are the first and second enzyme in the liver involved in the reaction that processes glucose?

A. Glucose 6 phosphatase AND Glucokinase
B. Hexokinase AND Phosphoglucose isomerase
C. Fructose 1,6 bisphosphatase AND Enolase
D. Glucokinase AND phosphoglucose isomerase
7. Upset with the way his government has neglected the country of Zimbabwe, a 30 year old man fasts in protest. At this point, his blood glucose level is at 60% of his normal. However, he has no lightheadedness. Despite his low blood glucose level, which alternative energy source is his brain using in order to maintain normal function?

A. Apoprotein B
B. Beta-carotene
C. C-reactive protein
D. Beta-hydroxybutyrate
E. Coenzyme A
8. A newborn begins vomiting after feeding, becomes severely jaundiced, and has liver disease. Treatment for possible sepsis is initiated, and the urine is found to have reducing substances. A blood screen for galactosemias positive, and lactose-containing substances are removed fromthe diet. Galactose is toxic in this case because

A. There is a deficiency of glucose in the extracellular space
B. Galactose is converted to the toxic substance galactitol (dulcitol)
C. Galactose inhibits gluconeogenesis leading to hyperglycemia
D. Galactose the sugar itself can become toxic and is most likely causing the jaundice
E. Galactose directly inhibits important regulatory enzymes with glucose metabolism
9. Which of the following is a part of all three pathways: glycogenolysis, glycolysis, and gluconeogenesis?

A. Glucose 1,6 Bisphosphate
B. Glucose-6-phosphate
C. Uridine diphosphoglucose
D. Fructose-1-phosphate
Board Style Questions
Arginine
takes place in the Urea Cycle
Urea accounts for 90% of nitrogenous waste excreted by the body
Arginine
Main source of ammonia from alanine and glutamine -> liver
Pi
Urea accounts for 90% of nitrogenous waste excreted by the body
The enzymes of the urea cycle are induced by a high protein diet
Two nitrogens are expelled in the Urea cycle, one from glutamate or alanine (forming ammonia), the other from aspartate
Key regulation: N-Acetylglutamate, whose synthesis is regulated by arginine
Aspartate is a key amino acid created from the TCA that is used in the urea cycle
Review:
Lysosomal enzymes
Serine
Threonine
Oxidation, Transamination, and Dephosphorylation
NH4+
H2SO4
(excreted in kidney)
When the cell needs more Ornithine for Urea Cycle transport, it's synthesized from glucose via glutamate.
There are eleven nonessential amino acids, named this as they can be synthesized from glucose: glutamate, glutamine, arginine, proline, aspartate, asparagine, serine, glycine, cysteine, alanine, and tyrosine.

The nonessential amino acids are made from either glycolysis or TCA intermediates

Essential amino acids (MUST be taken in by diet) are: phenylalanine, valine, threonine, tryptophan, isoleucine, methionine, histidine, leucine, lysine. MNEUMONIC: PVT TIM HLL (private tim hall)

Note that tyrosine isn't essential, but it must be MADE by an essential amino acid.

Following is a walkthrough of the pathways of amino acid SYNTHESIS and DEGRADATION
H2O
NAD+
The Glutamate DH rxn above shows why ammonia is so toxic: its accumulation pushes the rxn to the right, causing loss of NADH and excess NAD+ (loss of Electron Transport Chain transporter!)
Amino Acid Degradation
Amino acids are broken down into two different byproducts, and through this can be considered either glucogenic, ketogenic, or both.
Glucogenic amino acids are degraded into pyruvate or TCA cycle intermediates
Ketogenic amino acids are degraded into either acetyl-CoA or acetoacetate
Both: Threonine, Isoleucine, Tryptophan, Phenylalanine, Tyrosine
Ketogenic only: Leucine and Lysine
Glucogenic only: the other 14 standard amino acids
REQUIRES vit. B12
REQUIRES vit. B6
Homocysteine Methyltransferase
REQUIRES vit. B12
Homogentisate oxidase
Formino-
glutamate
(FIGlu)

Various Fatty Acids
Pyruvate Dehydrogenase
TAG
2-MAG
CoA
CoA-SH
1,2-DAG
Apoprotein
(esp apo B-100)
CoA
CoA-SH
Fatty Acid
TAG
Apoproteins
Other lipids
Chylomicrons
VLDL
Tetrahydrofolate (THF)
formamino THF
IDL
LDL
Cholesterol
Alanine
Glutamine
Triacyle Gylcerol
ATP
AMP + PPi
CoASH
Activating Step
Fatty Acyl CoA
FAD
Acyl CoA
Dehydrogenase
FADH2
trans 2 Fatty Enoyl CoA
Enoyl CoA
Hydratase
NAD+
NADH
H2O
L-Beta-Hydroxy acyl CoA
Beta-Hydroxy acyl CoA
Dehydrogenase
Beta-Keto acyl CoA
Enoyl CoA
Hydratase
H2O
Fatty acyl CoA + Acetyl CoA
Repetition

At the end of one round, the Fatty Acid CoA has two less Carbons

These four steps of Beta-Oxidation are repeated for the entire length of the Fatty Acid. The very last step simply produces two acetyl CoAs.

* Important * - 16 Carbon palmitoyl CoA carries out seven repetions of these basic four steps.
ATP Counting

Begining with a 16 Carbon Palmitoyl, seven FADH2 (7x2 ATP), seven NADH (7x3 ATP), 8 Acetyl CoA (8x12)

Remember, different Fatty Acids will yield different ATP amounts.
Oxidation of Odd- Chain and Unsaturated Fatty Acids

1. Odd Chain: The same four steps are repeated until the
the last cleavage which results in an Acetyl CoA and
Propionyl CoA. Propionyl CoA can be converted to
Glucose

2. Unsaturated Fatty Acids: Simply put, when a double
bond is reached it must be put in the alpha-beta trans
position. Once there, B-oxidation can proceed normally
Fatty Acid CoA
Carnitine
Fatty Acid
CoA-Carnitine
Fatty Acid CoA
CoASH
Lysosomal enzymes
Fatty Acid CoA
Carnitine
FA-Carnitine
Fatty Acid CoA
CoASH
Beta- Oxidation
Clinical Correlates
Board Style Review Questions
1. A young man arrives in your clinic complaining of fatigue when going about his normal job as a construction worker. Upon physical examination, the patient is found to have corneal opacities and angiokeratomas. He also mentions that a close family member has the same colored spots on their body. Based on this patient's symptoms, which family member is most likely to be affected?

(A) His father
(B) His mother
(C) His sister
(D) His son
(E) His maternal uncle
2. A 2-month-old child presents with signs of developmental delay, hepatosplenomegaly, cherry-red spots on their macula. Which enzyme is likely to be deficient in this patient?

(A) Hexosaminidase A
(B) Galactocerebrosidase
(C) Sphingomyelinase
(D) Arylsulfatase A
(E) Lipoprotein lipase
Fatty Acid and glycerol
Stored in adipose tissue
TAG
alpha-Linoleate (unsaturated)
Arachidonic acid
Other eicosanoids (PGEs, TXs, LT)
Glycerol and Malate Transport Systems
Fatty acid-CoA
1,2-DAG
Pi
Phosphatidic acid
Fatty acid-CoA
Glycerol-3-P
Glycerol
Glycerol kinase
ATP
ADP
NADH
NAD+
DHAP
Clinical Correlates
1. Several members of a family have an autosomal recessive disease characterized by intellectual deterioration, weakness, ataxia, seizures, and death at a young age. Special studies demonstrate a deficiency of cytochrome C oxidase activity. Which of the following subcellular organelles is defective in affected members of this family?
(A) Golgi apparatus
(B) Lysosomes
(C) Mitochondria
(D) Ribosomes
(E) Smooth endoplasmic reticulum




2. A 36-year-old Greek man with viral pneumonia has a self-limiting episode of hemolysis. Over the next week, he has an increased rate of reticulocytosis. Which of the following compounds serves as a precursor to heme in the reticulocytes?
(A) -Ketoglutarate
(B) Fumarate
(C) Isocitrate
(D) Oxaloacetate
(E) Succinyl-CoA
1. A 5-year-old boy has temporary weakness and cramping of skeletal muscle after exercise. He has normal mental development. This child most likely has a deficiency of which of the following enzymes?

(A) α-1,4-Glucan transferase
(B) Glycogen phosphorylase
(C) Glycogen synthase
(D) Phosphoglucomutase
(E) UDP-glucose pyrophosphorylase
Fatty acid-CoA
Adipose tissue
Liver
Lipoprotein Metabolism







10. A Zimbabwean medical student studying in the United States develops hemolytic anemia after taking the oxidizing sulfa antibiotics for an infection.What pathology is this caused by:

A. Glucose-6-phosphate dehydrogenase deficiency
B. Concomitant scurvy
C. Vitamin C deficiency
D. Diabetes
E. Glycogen phosphorylase deficiency



In Liver: ATP & Glucose 6-Phosphate
In Muscle: ATP & Glucose 6- Phosphate

An important way to collect Nitrogen, as mentioned, is with Glutamine. Glutamine can be created through alpha ketoglutarate, the TCA intermediate.
In Liver: Glucose 6 Phosphate
In Muscle: Glucose 6 Phosphate
NADH
ATP
ADP
Calcium
NADH
Succinyl CoA
Calcium
Citrate
NADPH
NADP+
Insulin
Glycogen Synthase a
Glycogen Synthesis
Glycogen Synthase b
Phosphorylase
kinase - P
Phosphorylase kinase
Protein Phosphorylase-1
Glycogen Phosphorylase a
Glycogen Synthase b
Glycogen Degradation
Apo CII
Apo E
From HDL
VLDL
Tissues (ie Adipose)
Capillary
1. Free Fatty Acids
2. Glycerol (to liver)
Extracellular
Lipoprotein Lipase
IDL
Apo C-II
Apo E
To HDL
LDL
Extra-Hepatic Tissue
Liver
VLDL
Step 1 - Liver produces
TAG rich VLDL
Step 2 - HDL donates Apo CII and ApoE
to VLDL
Step 3 - Because adipose
has access to apo C-II now
it removes TAG from VLDL
Step 4 - IDL was formed from
loss of TAG. IDL then gives back
Apo C II and Apo E to HDL to form
LDL
Step 5 - LDL binds and are
endocytosed into
Liver and other tissue
Chylomicrons are formed in the gastrointestinal tract after the consumption of fatty foods

Step 1 - Nascent Chylomicrons are donated Apo C-II and Apo E from HDL (similar to lipoprotein metabolism)

Step 2- These chylomicrons are transported through capillaries in adipose tissue and release TAG (similar to lipoprotein metabolism).

Step 3 - Apo C-II is returned to HDL and a chylomicron remnant is formed.

Step 4 - Chylomicron remnant returns to the liver for further metabolism.
Now, Time For Lipid Metabolism!!
From Diet
Clinical Correlates
1. Liver aminotransferases catalyze an important reaction that leads to the formation of an ammonium ion. This ammonium ion is excreted through the urea cycle as urea. In the production of the ammonium ion, an alpha amino group is added to _______ to form alpha-ketoglutarate?
a. Aspartate
b. Alanine
c. Oxaloacetate
d. Glutamate
e. Pyruvate
2. Chylomicrons, IDLs, LDLs, and very-low-density lipoproteins VLDLs make up a group that are classified as serum lipoproteins. Put the serum lipoproteins in ascending order of % triglycerides.
a. LDLs, IDLs, VLDLs, chylomicrons
b. Chylomicrons, VLDLs, IDLs, LDLs
c. VLDLs, IDLs, LDLs, chylomicrons
d. Chylomicrons, IDLs, VLDLs, LDLs
e. LDLs, VLDLs,, Chylomicrons, IDLS
3. A 2 y/o M infant has experienced severe weakness, mental retardation, and blindness. Labs were drawn and showed normal amounts of glycosaminoglycans and elevated ganglionside GM2. Which of the following enzyme defects might explain the infant’s phenotype?
a. Hexosaminidase A
b. Glucocerebrosidase
c. -L-iduronidase
d. -galactocerebrosidase
e. -gangliosidase A
4. Which one of the following apolipoproteins is found on the surface of VLDLs?
a. AI
b. B100
c. B48
d. E2
e. CI
5. Which biochemical pathway, if diminished, will hinder the synthesis of fatty acids?
a. The TCA
b. Gluconeogenesis
c. Mitochondrial malate dehydrogenase
d. The PPP
6. In which step does glycerol, a product of lipolysis of TAG, enter the glycolysis/gluconeogenesis cycle?
a. The level of Fructose 2,6 bisphosphate
b. Pyruvate
c. Citrate
d. Glucose 6 phosphate
e. Triose phosphates
7. A deficiency in the following would have the least significant effect on the synthesis of fatty acids?
a. FADH2
b. NADPH
c. Cobalamin
d. HCO3
e. AMP
8. A large portion of American society over the age of 50 take statins to prevent heart disease. What is the specific effect that statins have on cholesterol?
a. Inhibits HMG CoA reductase which results in Low blood glucose
b. Activates HMG CoA reductase which results in Low blood glucose
c. Inhibits HMG CoA reductase which results in Low blood LDLs
d. Activates HMG CoA reductase which results in Low blood LDLs
e. Inhibits HMG CoA reductase which results in High blood cholesterol
f. Activates HMG CoA reductase which results in High blood cholesterol
g. Inhibits HMG CoA reductase which results in Low oxidation of fatty acids
h. Activates HMG CoA reductase which results in Low oxidation of fatty acids
i. Activates HMG CoA reductase which results in Ketosis
j. Inhibits HMG CoA reductase which results in Lipolysis
9. The first two steps in cholesterol and ketone synthesis involved the synthesis of 3-hydroxy-3-methylglutaryl CoA. Where in the cell does this process take place?
a. In both the cytosol and mitochondria
b. Only in the cytosol of liver tissue
c. Only in mitochondria of liver tissue
d. Only in the mitochondria in all body tissue
e. Only in lysosomes
Board Style Questions
d. Glutamate
a. LDLs, IDLs, VLDLs, chylomicrons
a. Hexosaminidase A
b. B100
d. The PPP
e. Triose phosphates
a. FADH2
c. Inhibits HMG CoA reductase which results in Low blood LDLs
a. In both the cytosol and mitochondria
10. In order to prevent the liver from wasting resources when synthesizing fatty acids, it must turn off its oxidation of fatty acids. By which mechanism does it accomplish this?
a. Inhibition by an end product
b. Activation of oxidative enzymes to eliminate other enzymes involved in the pathway
c. Decreases in adipocyte lipolysis through gene regulation
d. Activation of an degradative enzyme
e. Inhibition of a translocation within the cell
e. Inhibition of a translocation within the cell
Chlyomicron Metabolism:
Chylomicrons are formed in the gastrointestinal tract after the consumption of fatty foods

Step 1 - Nascent Chylomicrons are donated to Apo C-II and Apo E from HDL (similar to lipoprotein metabolism)

Step 2- These chylomicrons are transported through capillaries in adipose tissue and release TAG (similar to lipoprotein metabolism).

Step 3 - Apo C-II is returned to HDL and a chylomicron remnant is formed.

Step 4 - Chylomicron remnant returns to the liver for further metabolism.
Now, Time for Amino Acid Metabolism!

UREA CYCLE GENERAL PRINCIPLES:
N-Acetylglucosamine (NAG) is a main regulator of the Urea Cycle, which will be stimulated by Arginine.
The Urea Cycle's main source of ammonia is from Alanine and Glutamine, shuttled to the liver.
The enzymes of the urea cycle are induced if a high protein diet is consumed, this is the major way of course to excrete excess nitrogen
Note that the proximal enzymes of the pathway, CPS1 and OTC, are found in the mitochondria. The other enzymes are found in the cytosol. Thus, citrulline must be shuttled out from the mitochondria, and ornithine must be shuttled in to the mitochondria.
UREA CYCLE: Final points
Aspartate is a key amino acid created from the TCA that is used in the Urea Cycle. It is the second source of nitrogen (ammonium is the first).
Fumarate is created from the Urea cycle, and shuttled back in to the TCA
Urea passes into the blood and is excreted by the kidneys
90% of nitrogenous waste leaves the body in the form of Urea


1. Where do the reactions of the urea cycle take place?
a. In lysosomes and the Endoplasmic Reticulum
b. In peroxisomes and occasionally lysosomes
c. In both the mitochondrial matrix and the cytosol
d. Only in the cytosol
e. Only in the mitochondrial matrix
2. A several day old patient becomes lethargic, cries inconsolably, and tachypneic a short time after feeding. Initially his APGAR scores were 9 and 10, but the patient has now become comatose with a faint response to stimuli. Lab values show hyperammonemia. Which of the following amino acids is likely increased in this patient's urea cycle disorder?
a. Proline
b. Tyrosine
c. Glutamine
d. Alanine
3. A deficiency in what molecule would most directly decrease the production of thyroxine (T4)?a. Tyrosineb. Threoninec. Melatonind. Adenosinee. Tryptophan
4. A deficiency of what would make tyrosine an essential amino acid?
a. Tryptophan
b. Serotonin
c. Norepinephrine
d. Phenylalanine
e. Cortisol
5. Which of the hormones would be deficient if the patient had very low phenylalanine
a. LH and FSH
b. Insulin
c. Epinephrine
d. ACE
e. Corticosteroids
6. A 45 y/o M with history of alcoholism and obesity comes into your clinic complaining of 10/10 pain in his big left first digit of his left leg. No history of trauma or signs of infection. The patient states he can hardly sleep at night because even the sheets touching his toe causes pain. What is the most likely deficiency causing this patient’s symptoms?
a. Increase in purine synthesis
b. Decreased pyrimidine synthesis
c. Decreased phosphoribosylpyrophosphate (PRPP) levels
d. Inhibition of HMG CoA reductase
e. Diminished urate synthesis
7. Which of the following would most likely not be a cause of hyperuricemia?
a. Xanthine oxidase hyperactivity
b. Ornithine transcarbamylase deficiency
c. Purine overproduction secondary to Von Gierke’s disease
d. Tophous Gout
e. Lesch-Nyhan syndrome
8. Which of the following contributes nitrogen to all the bases of DNA?
a. Carbon Monoxide
b. Glutamate
c. Carbamoyl phosphate
d. Aspartate
e. Vitamin B12
9. Where do the reactions of the urea cycle occur in the cell
a. In the mitochondrial matrix and the cytosol
b. In the cytosol
c. In the mitochondrial matrix
d. Only in the rough endoplasmic reticulum
e. In lysosomes and peroxisomes
Board Style Questions
In both the mitochondrial matrix and the cytosol
c. Glutamine
a. Tyrosine
d. Phenylalanine
c. Epinephrine
c. Decreased phosphoribosylpyrophosphate (PRPP) levels
b. Ornithine transcarbamylase deficiency
d. Aspartate
a. In the mitochondrial matrix and the cytosol
10. Which of the following amino acids is increased in homocystinuria?
a. Histidine
b. Proline
c. Threonine
d. Methionine
e. Alanine
D. Methionine
11. A 14 year old male comes to the clinic with complaints of muscle cramping after sprinting drills in high school gym class. He is a nonsmoker, mildly obese, and generally avoided physical activity throughout grade school. No other abnormalities are noted on physical exam. After laboratory tests, Creatine Kinase is noted to be elevated. What is the enzyme deficiency responsible for this patient’s rapid fatigue?
a. Glycogen Phosphorylase
b. Glycogen Synthase
c. Carnitine Palmitoyl Transferase II
d. alpha-1,4 Glucosidase
e. alpha-1,6 Glucosidase
12. A lethargic newborn is found to have hepatomegaly. After a basic metabolic panel is ordered, the patient is noted to be hypoglycemic. The newborn is given overnight feeds via a nasogastric tube, however the patient continues to demonstrate consistently low blood sugars. A liver biopsy is performed. Molecular studies reveal a normal glycogen structure, and a low amount of glycogen phosphorylase. What is the normal function of this enzyme?

a. Transfer of glucose from UDP-glucose onto the nonreducing end of a glycogen molecule.
b. Removal of a glucose residue from the nonreducing ends of a glycogen molecule.
c. Transfer of a glucose trisaccharide chain to a nonreducing end of a different chain on the glycogen molecule.
d. Hydrolyze an alpha-1,6 bond of glycogen
13. In the previous question, what disease does the patient have?
a. Pompe’s disease
b. Cori’s disease
c. Andersen’s disease
d. McArdle’s disease
e. Hers’ disease
14. A similar patient to the newborn in question #2 presents to the hospital. After a liver biopsy and molecular studies, the glycogen structure appears abnormal; there are few long chains with very few branches noted. What disease does the patient have?
a. Pompe’s disease
b. Cori’s disease
c. Andersen’s disease
d. McArdle’s disease
e. Hers’ disease
Glycogen Phosphorylase
b. Removal of a glucose residue from the non-reducing ends of a glycogen molecule.
Hers’ disease
c. Andersen’s disease
15. An infant is found to have mental retardation, hypotonia, and cardiomegaly. Which enzyme is likely deficient in this patient?
a. Glycogen Phosphorylase
b. Glycogen Synthase
c. Carnitine Palmitoyl Transferase II
d. alpha-1,4 Glucosidase
e. alpha-1,6 Glucosidase
d. alpha-1,4 Glucosidase
Thank You and We Hope You Found This Helpful!

References:
1. Agabegi, Steven, and Agabegi, Elizabeth. Step Up to Medicine third edition. Baltimore: Lippincott Williams and Wilkins, 2013. Print.

2. Giugliani R, Federhen A, Rojas MV et al. Mucopolysaccharidosis I, II, and VI: Brief review and guidelines for treatment. Genet Mol Biol. Oct 2010;33(4):589-604.

3. Harvey, Richard, and Ferrier, Denise. Biochemistry fifth edition. Philadelphia: Lippincott Williams & Wilkins, 2011. Print.

4. Le, Tao, and Bhushan, Vikas, and Vasan, Neil. First Aid for the USMLE Step 1. New York: McGraw Hill Medical, 2010. Print.

5. Segel GB. Enzymatic defects. In: Kliegman RM, Stanton BF, St. Geme J, Schor N, Behrman RE, eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, Pa: Saunders Elsevier; 2011:chap 457.
Welcome to Prezi Biochemistry!

Included in this Prezi are the Carbohydrate, Amino Acid, and Lipid Metabolic pathways; important and board relevant clinical correlates; and review questions.


Instructions on how to utilize Prezi Biochemistry:

The best way to use Prezi Biochemistry is to follow the predetermined path. This can be found by moving your mouse to the bottom of the screen and moving along the line. Don't be afraid to explore off the path in order to maximize your understanding of just how integrated our biochemical pathways are. It is especially useful to see how the protein/amino acid metabolism interacts with carbohydrate metabolism. Remember, that when you stray off of the path, all you have to do is hit the right arrow button and you will return to the next slide from where you left the path. It is important to click through the entire path, because their is information that would otherwise be impossible to find.

There are clinical correlates throughout the prezi that can usually be found within the title of the pathway, otherwise follow the path and you will get to all of them.

There are also review questions that are usually found immediately after the clinical correlates.
The NADPH produced here serves an important role in antioxidant reactions within the cell, which protect it from oxidative damage:

1. Reduced glutathione detoxifies hydrogen peroxide (hydrogen peroxide is capable of causing oxidative damage).

2. At the end of the reaction hydrogen peroxide is transformed into 2 harmless water molecules, but at a cost to the glutathione. The glutathione is now in the oxidized state and cannot help the cell to fight against the next hydrogen peroxide.

3. The enzyme glutathione reductase uses NADPH to convert glutathione back into it's reduced form.
(In most tissue)
(In Liver and Beta-islet cells of the pancreas)
Hexokinase has low Km

Glucokinase has high Km
Important to note that this is the rate limiting step of Glycolysis!
Full transcript